Creationist Derail From Evolving Fish Thread

[questioner121]

Yes, I think he rather did, didn't he? Said something like, Is that a problem? and scarpered. Well, yes Questioner121, it is. It is a big problem that big sky daddy fucks up big time in, e g, saddling a person with neurofibromatosis. Or, even, fucking up the guidance system of razor bills so that they get off course and starve to death. Not a nice way to die, I'd say. Sky daddy simply is not a very pleasant person to have running things, don't you agree?

Like I said before, you haven't long before you do find out.

[ADParker]

I think gene mutations are 'natural' but for a gene mutation to actually develop a well functioning trait is something that is unusual to say the least. If you look at the genetic level, a mutation to create, let's say for example, an extra digit on a persons hand doesn't just mean creating an extra finger but also wiring it up to the brain, plugging it into the blood circulation system, maintaining it, etc.

Ah. A common misunderstanding for those without the requisite understanding of genetics (which only need be at a lay man level.)

Such a mutation can be 'big bang' as you put it; one single mutation resulting in an extra digit.
The thing is questioner121; that in this case the 'genetic code' for "building" digits is already in place. The organism already has a number. Let's use humans with five for our example. All that happens is that the mutation results in, to use computer code analogies, the function "grow a digit" to be called 6 times instead of five, or the "make a digit" code is repeated (gene duplication) such that it is called an extra time at some point. This "make a digit" function simply calls of the already existing subroutines (other genes) with control how that digit is made. It doesn't have to include any 'information' on how to go about building that digit.

To further look into the computer coding analogy; this is something programmers do all the time, especially in complex programs; they build or copy the code for performing a certain action, then all they have to do is add a relatively simple function to 'call' that code a specific number of times (perhaps with certain parameters that are variables in that code.)

An example of experimenting with this is when geneticists took such a "call function" bit of DNA from a mouse, and inserted it in the DNA of a fly, specifically in a region known to code for building the knee joints of those flies.
The result: The resulting fly grew an extra eye on it's knee! Not a mouse eye though (neither in scale or features), but a perfectly ordinary fly eye. Because the 'call' function to "build an eye" was basically the same in both species (rodent/mammal and insects, quite the divide), only the related specific codes for how to build those eyes where quite different.

I can understand it if evolutionists think it's perfectly naturally for animals in a population to have an extra digit here or there, different coloured skins, different shaped beaks, etc. But I don't think evolutionists understand that it's not a simple matter of a genetic mutation at the molecular level. It needs to encompass a significant proportion of the animals DNA in order to make the genetic mutation viable.

This is because you fail to realize that for the most part mutations are relatively minor in effect, they may code for a single protein for example (and in the rare cases where they are not; they tend to be terminal.) And that all the related things that have to go on, such as all the detail work of attaching that extra digit up to all it needs to right places (nerves, blood vessels...) are functions already in place that are already 'programmed' to run when called.

[Varangian]

Au contraire, questioner - you'll have to wait all your life for that non-event, and on your death-bed you'll hopefully not realise that you've wasted your life worshipping a fantasy character. Religion is mind-rot, and Islam is among the worst religions.

[Shrunk]

But seriously, Questioner121, how do you find the genetic diseases that Agrippina listed compatible with the belief that evolution is directed by a "benevolent" and "omnipotent" god? I think you have just run up against the good old theodice problem.

Again.

It's quite simple. Life is not in the control of humans or any other creation. Whatever happens in the world does so because it is allowed to happen. Why it happens is not always known to humans. As muslims we just have to accept it with faith. If everything nice happened in the world and there was never any suffering or lying or bad things and humans were told that bad things could happen to them they'd ask for proof. They'd want to see the evidence.

This life is temporary. All life is here for a very short amount of time. What matters is what kind of life you get after death. So no matter how much you suffered, or even how great a life you had in this world it will pale into insignificance compared to the life after death.

I want to see the evidence.

You say Allah provides us evidence of "bad things" because otherwise we wouldn't believe they exist. So why does he not provide us evidence of the afterlife?

(And you still ignore the question of why Allah, according to the mythology you believe in, causes those "bad things" to exist in the first place. It's a very bizarre form of reasoning that says "Bad things exist, because if bad things did not exist, then no one would believe bad things exist." )

[Spearthrower]

What matters is what kind of life you get after death.

There you have it!

The biggest lie ever manufactured for human consumption.

Giving up the one and only thing you can be guaranteed of for an absurdly childish fantasy in Neverneverland.

You couldn't possibly express a more anti-intellectual, trite piece of shite had you spent time thinking about it, which you clearly haven't to have accepted this bollocks in the first place.

[Calilasseia]

I think I'm beginning to understand

The content of your posts says otherwise.

where the evolutionists

Oh no, it's that tiresome creationist canard ...

The "evolutionist" canard (with "Darwinist" side salad).

Now, if there is one guaranteed way for a creationist to establish that he or she is here for no other reason than to propagandise for a doctrine, it's the deployment of that most viscerally hated of words in the lexicon, namely, evolutionist. I have posted about this so often here, that I was surprised to find that I'd missed it out of the original list, but I had more pressing concerns to attend to when compiling the list originally. However, having been reminded of it, now is the time to nail this one to the ground with a stake through its heart once and for all.

There is no such thing as an "evolutionist". Why do I say this? Simple. Because the word has become thoroughly debased through creationist abuse thereof, and in my view, deserves to be struck from the language forever. For those who need the requisite education, there exist evolutionary biologists, namely the scientific professionals who devote decades of their lives to understanding the biosphere and conducting research into appropriate biological phenomena, and those outside that specialist professional remit who accept the reality-based, evidence-based case that they present in their peer reviewed scientific papers for their postulates. The word "evolutionist" is a discoursive elision, erected by creationists for a very specific and utterly mendacious purpose, namely to suggest that valid evolutionary science is a "doctrine", and that those who accept its postulates do so merely as a priori "assumptions" (see [3] above). This is manifestly false, as anyone who has actually read the peer reviewed scientific literature is eminently well placed to understand. The idea that there exists some sort of "symmetry" between valid, evidence-based, reality-based science (evolutionary biology) and assertion-laden, mythology-based doctrine (creationism) is FALSE. Evolutionary biology, like every other branch of science, tests assertions and presuppositions to destruction, which is why creationism was tossed into the bin 150 years ago (see [2] above). When creationists can provide methodologically rigorous empirical tests of their assertions, the critical thinkers will sit up and take notice.

Furthermore, with respect to this canard, does the acceptance of the scientifically educated individuals on this board, of the current scientific paradigm for gravity make them "gravitationists"? Does their acceptance of the evidence supporting the germ theory of disease make them "microbists"? Does their acceptance of the validity of Maxwell's Equations make them "electromagnetists"? Does their acceptance of of the validity of the work of Planck, Bohr, Schrödinger, Dirac and a dozen others in the relevant field make them "quantumists"? Does their acceptance of the validity of the astrophysical model for star formation and the processes that take place inside stars make them "stellarists"? If you are unable to see the absurdity inherent in this, then you are in no position to tell people here that professional scientists have got it wrong, whilst ignorant Bronze Age nomads writing mythology 3,000 years ago got it right.

While we're at it, let's deal with the duplicitous side salad known as "Darwinist". The critical thinkers here know why this particular discoursive elision is erected, and the reason is related to the above. Basically, "Darwinist" is erected for the specific purpose of suggesting that the only reason people accept evolution is because they bow uncritically to Darwin as an authority figure. This is, not to put too fine a point on it, droolingly encephalitic drivel of a particularly suppurating order. Let's provide a much needed education once and for all here.

Darwin is regarded as historically important because he founded the scientific discipline of evolutionary biology, and in the process, converted biology from a cataloguing exercise into a proper empirical science. The reason Darwin is considered important is NOT because he is regarded uncritically as an "authority figure" - the critical thinkers leave this sort of starry-eyed gazing to followers of the likes of William Lane Craig. Darwin is regarded as important because he was the first person to pay serious attention to reality with respect to the biosphere, with respect to the business of determining mechanisms for its development, and the first to engage in diligent intellectual labour for the purpose of establishing that reality supported his postulates with respect to the biosphere. In other words, instead of sitting around accepting uncritically mythological blind assertion, he got off his arse, rolled up his sleeves, did the hard work, put in the long hours performing the research and gathering the real world data, and then spending long hours determining what would falsify his ideas and determining in a rigorous manner that no such falsification existed. For those who are unaware of this, the requisite labour swallowed up twenty years of his life, which is par for the course for a scientist introducing a new paradigm to the world. THAT is why he is regarded as important, because he expended colossal amounts of labour ensuring that REALITY supported his ideas. That's the ONLY reason ANY scientist acquires a reputation for being a towering contributor to the field, because said scientist toils unceasingly for many years, in some cases whole decades, ensuring that his ideas are supported by reality in a methodologically rigorous fashion.

Additionally, just in case this idea hasn't crossed the mind of any creationist posting here, evolutionary biology has moved on in the 150 years since Darwin, and whilst his historical role is rightly recognised, the critical thinkers have also recognised that more recent developments have taken place that would leave Darwin's eyes out on stalks if he were around to see them. The contributors to the field after Darwin are numerous, and include individuals who contributed to the development of other branches of science making advances in evolutionary theory possible. Individuals such as Ronald Fisher, who developed the mathematical tools required to make sense of vast swathes of biological data (heard of analysis of variance? Fisher invented it), or Theodosius Dobzhansky, who combined theoretical imagination with empirical rigour, and who, amongst other developments, provided science with a documented instance of speciation in the laboratory. Other seminal contributors included Müller (who trashed Behe's nonsense six decades before Behe was born), E. O. Wilson, Ernst Mayr, Motoo Kimura, Stephen Jay Gould, Niles Eldredge, J. B. S. Haldane, Richard Lewontin, Sewall Wright, Jerry Coyne, Carl Woese, Kenneth Miller, and they're just the ones I can list off the top of my head. Pick up any half-decent collection of scientific papers from the past 100 years, and dozens more names can be added to that list.

So, anyone who wants to be regarded as an extremely low-grade chew toy here only has to erect the "evolutionist" or "Darwinist" canard, and they will guarantee this end result.

Read the above and learn from it.

on this forum are coming from. They assume

Wrong again. We don't "assume" anything. We leave assumptions, and for that matter, blind assertions and presuppositions, to supernaturalists.

that variations in animals is natural

It is. Are you identical to either of your parfents? No? There's part of your evidence. Moreover, if you pick up an actual biology textbook, and look up meiosis, you'll find reasons for the emergence of variation in offspring (at least, in sexually reproducing organisms) arising from the mechanism by which genes are shuffled when germ cells are made.

so it's perfectly possible to have a mutations which give birds a navigation system, for zebras to have stripes, for peacocks to have extravagant feathers, etc.

And lo and behold, we have evidence for countless thousands of mutations. I'm aware of several mutations in just one species of tropical fish that have appeared during the 100 years or so of its domestication in the aquarium. What's more, many of the genes in question are known to obey well-defined inheritance mechanisms. The Double Tail mutation in Betta splendens is autosomal recessive, and obeys the Mendelian laws of inheritance for single-factor mutations.

The only thing I'm unclear is on are these mutations big bang or did they develop gradually over millions of years?

Actually, any mutation (and it has to be a mutation in a germ cell, in order for it to be passed on to offspring) can occur at any moment. What takes time is the fixation of a mutation in a population, once that mutation has been disseminated to offspring. Which depends upon the strength of the selection pressure leading to fixation thereof. Mutations that are subject to strong selection pressures will achieve fixation in a population in a relatively small number of generations (usually, one is looking at somewhere between 50 and 100 generations for this to take place). If the organism in question has a fast turnaround, and produces a new generation every month, then fixation can occur in less than 5 years if the selection pressure is long enough, If, on the other hand, the organism in question takes 20 years to produce a new generation, then fixation won't occur until after something like 2,000 years has elasped, and that's if we're dealing with a strong selection pressure. A weak selection pressure will increase the time for each case.

Did bird migration start of with a basic navigation system, did the zebras start of having grey stripes which deepened to black, did the peacock start off having 1 feather which then became 100+?

Are you incapable of finding this out for yourself? Google Scholar will point you to thousands of scientific papers if you bother to use it.

I think gene mutations are 'natural' but for a gene mutation to actually develop a well functioning trait is something that is unusual to say the least.

No it isn't. Do I have to bring the Double Tail mutation in Betta splendens here to demonstrate this?

If you look at the genetic level, a mutation to create, let's say for example, an extra digit on a persons hand doesn't just mean creating an extra finger but also wiring it up to the brain, plugging it into the blood circulation system, maintaining it, etc.

So what? This is familiar stuff to those who bothered to learn about regulatory networks and evo-devo. You'll also find that there are quite a few humans on the planet with extra digits (a condition known as polydactyly). Here's an x-ray of a human foot with 6 toes, for example:



Here's an x-ray of a human hand with 6 fingers:



Plus, polydactyly is observed fairly frequently in various cat breeds. Here's a news item featuring a polydactyl cat. Cats normally have five toes on the front paws, and four on the rear. This cat has 7 on the front, and 6 on the rear. All of them fully operational. Indeed, in the past, polydactyl cats were regarded as not only being omens of good luck amongst sailors in the days of sailing ships, but were valued for their enhanced climbing ability and rodent hunting skills.

None of this is a problem for those of us who bothered to study actual biology.

I can understand it if evolutionists

Yawn. Read my above destruction of the tiresome "evolutionist" canard.

think it's perfectly naturally for animals in a population to have an extra digit here or there, different coloured skins, different shaped beaks, etc. But I don't think evolutionists understand that it's not a simple matter of a genetic mutation at the molecular level.

The evidence says otherwise. The Double Tail mutation in Betta splendens is centred upon a single gene, one that exhibits classic Mendelian inheritance.

It needs to encompass a significant proportion of the animals DNA in order to make the genetic mutation viable.

Wrong. Do I have to bring the Double Tail mutation in Betta splendens here, in order to establish that you are wrong?

How can you be unclear on how the mutations came about, have you not read any of what has been posted or the links to other information?

Sorry I didn't see any link which describes how a mutation develops at the genetic level. The links just pointed to what mutations are observed in nature and then whole load of speculation as to how they could have been naturally selected for.

Oh please, go and pick up an actual science textbook. Scientists have catalogued numerous chemical reactions that result in mutations. The classic example being methylation of a cytosine molecule in a DNA strand, to form 5-methylcytosine, followed by deamination of that molecule, which results in the molecule changing to thymine, a different chemical base. A C->T change in a DNA strand can have profound effects. For example, changing a C to a T in a CGA codon (which normally codes for the amino acid arginine) results in the codon becoming a stop codon, and signalling termination of protein synthesis. Change the C in a CTT codon (normally coding for leucine) to a T (resulting in a TTT codon, coding for phenylalanine) and the resulting protein could have a significantly altered function, depending upon whether or not that amino acid is in a critical region.

Then of course, there are other classes of mutations apart from point mutations, such as insertion and deletions (indels), frameshift mutations (responsible for nylonase in Japanese Flavobacterium) and whole gene duplications (which resulted in the emergence of antifreeze glycoproteins in Antarctic Notothenioid fishes, when the duplicated trypsinogen gene acquired mutations that resulted in the protein coded for possessing a new function).

Basically the entire explanation on the diversity of life from 'simple' cell organisms to multi cell organisms relies on mutations to present within any given population. And that's it. Nothing else. The direction of the diversity of organism population is then based on NS or some other mechanism.

You do realise we have evidence for the emergence of multicellularity from single celled organisms? It's been observed in the laboratory, and the effect can be produced releatably and reliably in laboratory experiments.

So when the evolutionists

Yawn.

reads thousands of papers on observations of genetic mutations and how they are selected for it immediately tells them that this is what happened 'billions' of years ago.

This might have something to do with the fact that we have zero evidence for the chemistry of life being different in the past. Indeed, if that chemistry was different in the past, then we would have inherited that chemistry. You do know what "inheritance" means, don't you?

Now that is just plain ridiculous.

No it isn't. It makes perfect sense to postulate that we inherited the same basic chemistry as the earliest life forms. Unless you can provide a detailed exposition of how a different chemistry could have been inherited, of course ...

How can someone make such a huge assumption?

It isn't an "assumption". How do we know this? Oh, that's right, various experiments have been conducted in the laboratory aimed at elucidating how that chemisttry arose. How many of the 116 or sso papers on this do you want me to bring here?

And then to go on and trumpet about how humans came from apes as a fact is even crazier.

Oh dear, you really never attended any science classes, did you?

I have news for you. Linnaeus, way back in 1747, thought humans and chimpanzees were suffficiently closely related, on the basis of comparative anatomy alone, for the two species to belong to the same taxonomic Genus. The reason he didn't do this was interference from religion, in an era when enforcers of conformtiy to doctrine had the power to destroy your life. Indeed, I've covered this in the past here on numerous occasions: Linnaeus wrote a letter to his fellow taxonomist, Johann Georg Gmelin, in 1747, lamenting this interference. The letter can be read in full online, courtesy of the University of Uppsala's publicly available version of the database containing the letters of Linnaeus here. The letter in question is this one, dated 25th February, 1747. I'll provide both the original Latin text of the relevant paragraph, and the English translation:

Non placet, quod Hominem inter ant[h]ropomorpha collocaverim, sed homo noscit se ipsum. Removeamus vocabula. Mihi perinde erit, quo nomine utamur. Sed quaero a Te et Toto orbe differentiam genericam inter hominem et Simiam, quae ex principiis Historiae naturalis. Ego certissime nullam novi. Utinam aliquis mihi unicam diceret! Si vocassem hominem simiam vel vice versa omnes in me conjecissem theologos. Debuissem forte ex lege artis.

The translation reads as follows:

It does not please (you) that I've placed Man among the Anthropomorpha,[22] but man learns to know himself. Let's not quibble over words. It will be the same to me whatever name we apply. But I seek from you and from the whole world a generic difference between man and simian that [follows] from the principles of Natural History. I absolutely know of none. If only someone might tell me a single one! If I would have called man a simian or vice versa, I would have brought together all the theologians against me. Perhaps I ought to have by virtue of the law of the discipline.

So Linnaeus, who was a de facto creationist (purely because there existed no other paradigm in his day), agreed that humans and chimpanzees were sufficiently closely related, to warrant their placement in the same taoxnomic Genus, yet was inhibited from doing so by religious interference in science. Of course this is not the only instance where the attitude of the religious has consisted of "conform or else", not is it the only instance of the religious insisting that doctrine is automatically right, regardless of whether or not reality agrees with this. But I digress. The simple fact is, comparative anatomists, creationists included, throughout the 18th and early 19th centuries, posited that relationships existed between different organismal taxa, on the basis of shared anatomical characteristics.

The master stroke Darwin provided, was to provide a mechanism for the appearance of those shared anatomical characteristics. Namely, inheritance from shared ancestors. Indeed, inheritance is of seminal importance throughout the early Abrahamic mythologies, which regale us with an abundance of tedious genealogical lists. Darwin's contribution consisted of extending genealogy across the entire biosphere. It's not as if we lack evidence for the existence of inheritance followed by divergence: every instance of selective breeding performed by humans, in pursuit first of ensuring a food supply via agriculture, provides evidence for this mechanism in action. There is no evidence whatsoever, that the relevant genetic mechanisms underpinning this operated in different ways in the past. Consequently, since we have evidence for inheritance followed by acquisition of new features (including documented instances of speciation in the scientific literature), it is entirely apposite to postulate that the same processes applied to organisms in the past, including fossil organisms. And, when those fossil organisms are subject to the same analysis of comparative anatomy applied to living organisms, we find patterns of the same class appearing again and again - common anatomical features being dispensed to later generations, then subject to stepwise modification.

The point being made here, of course, is that even if no fossils had ever been found, the evidence from living organisms is sufficient to make the case for evolution, because the analysis of those fossils derives from work performed on present day living organisms. Fossils are simply the icing on the cake. Even more importantly, when the underlying biochemical basis for genetics was alighted upon, the potential existed for that discovery to falsify evolutionary postulates on a grand scale. But oh, that's right, it didn't falsify evolutionary postulates, it reinforced them. Hence the Modern Synthesis.

Oh, and the evidence from the genomes of the two species merely reinforces this.

Let's take a look at a relevant scientific paper, shall we? Namely this one:

Initial Sequencing Of The Chimpanzee Genome And Comparison With The Human Genome, The Chimpanzee Genome Sequencing Consortium (see paper for full list of 68 authors), Nature, 437: 69-87 (1 September 2005) [Full paper downloadable from here]

Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.

Let's take a look at the detailed findings, shall we?

Here we report a draft sequence of the genome of the common chimpanzee, and undertake comparative analyses with the human genome. This comparison differs fundamentally from recent comparative genomic studies of mouse, rat, chicken and fish14–17. Because these species have diverged substantially from the human lineage, the focus in such studies is on accurate alignment of the genomes and recognition of regions of unusually high evolutionary conservation to pinpoint functional elements. Because the chimpanzee lies at such a short evolutionary distance with respect to human, nearly all of the bases are identical by descent and sequences can be readily aligned except in recently derived, large repetitive regions. The focus thus turns to differences rather than similarities. An observed difference at a site nearly always represents a single event, not multiple independent changes over time. Most of the differences reflect random genetic drift, and thus they hold extensive information about mutational processes and negative selection that can be readily mined with current analytical techniques. Hidden among the differences is a minority of functionally important changes that underlie the phenotypic differences between the two species. Our ability to distinguish such sites is currently quite limited, but the catalogue of human–chimpanzee differences opens this issue to systematic investigation for the first time.We would also hope that, in elaborating the few differences that separate the two species, we will increase pressure to save chimpanzees and other great apes in the wild.

Our results confirm many earlier observations, but notably challenge some previous claims based on more limited data. The genome-wide data also allow some questions to be addressed for the first time. (Here and throughout, we refer to chimpanzee–human comparison as representing hominids and mouse–rat comparison as representing murids—of course, each pair covers only a subset of the
clade.) The main findings include:

. Single-nucleotide substitutions occur at a mean rate of 1.23% between copies of the human and chimpanzee genome, with 1.06% or less corresponding to fixed divergence between the species.

. Regional variation in nucleotide substitution rates is conserved between the hominid and murid genomes, but rates in subtelomeric regions are disproportionately elevated in the hominids.

. Substitutions at CpG dinucleotides, which constitute one-quarter of all observed substitutions, occur at more similar rates in male and female germ lines than non-CpG substitutions.

. Insertion and deletion (indel) events are fewer in number than single-nucleotide substitutions, but result in ~1.5% of the euchromatic sequence in each species being lineage-specific.

. There are notable differences in the rate of transposable element insertions: short interspersed elements (SINEs) have been threefold more active in humans, whereas chimpanzees have acquired two new families of retroviral elements.

. Orthologous proteins in human and chimpanzee are extremely similar, with ~29% being identical and the typical orthologue differing by only two amino acids, one per lineage.

. The normalized rates of amino-acid-altering substitutions in the hominid lineages are elevated relative to the murid lineages, but close to that seen for common human polymorphisms, implying that positive selection during hominid evolution accounts for a smaller fraction of protein divergence than suggested in some previous reports.

. The substitution rate at silent sites in exons is lower than the rate at nearby intronic sites, consistent with weak purifying selection on silent sites in mammals.

. Analysis of the pattern of human diversity relative to hominid divergence identifies several loci as potential candidates for strong selective sweeps in recent human history.

So, according to the actual research scientists who analysed the chimpanzee genome, it has been found that around twenty nine percent of the orthologous proteins of the two species are IDENTICAL, with the remainder differing by just one or two amino acids. This finding only makes sense, along with several other findings, if one postulates that the genes in question were inherited from a common ancestor. I'll deal with retroviral insertions in a moment. But first, I want to deal with another matter, namely the work on human chromosome 2, which has been found to be the result of a chromosome fusion event in the past, after the human and chimpanzee lineages split from our common ancestor. Here's evolutionary biologist Ken Miller explaining the findings in a video clip - I'll post the full transcript after the video:

[youtube]http://www.youtube.com/watch?v=Gs1zeWWIm5M[/youtube]

The second thing that you saw at the trial, was that when data was introduced at the trial, which I and another witness introduced from whole genome sequencing, the intelligent design advocates just literally had nothing to say. We weren't asked questions in cross-examination, the other side never brought it up, they never argued against it, they just left it. Here's an example.

Many of you may know that a few months ago the genetic code of the chimpanzee was published. Therefore we can compare our genome to these primate relatives. What do we find? I want to show you one striking finding that dates to about a year ago. You all know that evolution argues that we share a common ancestor with the great apes - the chimpanzee, the gorilla and the orang-utan. Well, if that's true there should be genetic similarities, and in fact there are. But there's something that's really interesting, and has the potential, if it were true, to contradict evolutionary common ancestry, and that is we have two fewer chromosomes than the other great apes - we have 46, they all have 48. That's very interesting. Now what does that actually mean? Well first of all, the 46 chromosomes that we have - you've got 23 from Mom and 23 from Dad, so it's actually 23 pairs - these guys have 24 from each parent so they have 24 pairs. So everybody in this room is missing a pair of chromosomes, so where did it go? Could if have gotten lost in our lineage? Ah-ah - if it got lost, if a whole primate chromosome was lost, that would be lethal. So there's only two possibilities, and that is if these guys really share a common ancestor, that ancestor either had 48 chromosomes or 46. Now if it had 48 - 24 pairs, which is probably true, because 3 our of 4 have 48 chromosomes - what must have happened is that one pair of chromosomes must have gotten fused. So we should be able to look at our genome, and discover that one of our chromosomes resulted from the fusion of two primate chromosomes. So we should be able to look around our genome, and you know what, if we don't find it, evolution is wrong - we don't share a common ancestor. So if - how would we find it?

Well, biologists in the room will know that the chromosomes have nifty little markers - they have markers called centromeres which are DNA sequences which are used to separate them during mitosis, and they have cool little DNA sequences on the ends called telomeres. What would happen if a pair of chromosomes got fused? Well what would happen is the fusion would put telomeres where they don't belong in the centre of the chromosome, and the resulting fused chromosome should actually have two centromeres. One of them might become inactivated, but nonetheless it should still be there. So we can scan our genome, and you know that if we don't find that chromosome, evolution's in trouble.

Well, guess what?

It's chromosome number 2.

Our chromosome number 2 was formed by the fusion of two primate chromosomes - this is the paper from Nature a little more than a year ago - and I put up a little of the paper, I'm sorry if it's technical but look at what it says! "Chromosome 2 is unique to our lineage. It emerged as a result of head-to-head fusion of two chromosomes that remain separate in other primates." Those of you who have not kept up with how much we know about the genome should pay attention to this because you'll be amazed at how precisely we can look at things ... the precise fusion site has been located at base number 114,455,823 to 114, 455, 838 ... in other words, within fifteen bases ... and you'll notice - multiple sub-telomere duplications - the telomeres that don't belong, and lo and behold, the centromere that is inactivated corresponds to chimp chromosome 13. It's there, it's testable, it confirms the prediction of evolution. How would intelligent design explain this? Only one way - by shrugging and saying "that's the way the designer made it" - no reason, no rhyme, presumably there's a designer who designed human chromosome number 2 to make it look as if it was formed by the fusion from a primate ancestor ... I'm a Roman Catholic, I'm a theist in the broadest sense, I would say that I believe in a 'designer', but you know what, I don't believe in a deceptive one, I don't believe in one who would do this to try to fool us, and therefore I think this is authentic - it tells us something about our ancestry.

And now, I shall return to retroviral insertions. These are snippets of viral genes, that appear in our genome, arising from the action of various retroviruses, courtesy of the interesting and unusual manner in which these viruses reproduce in host cells. Since the genomes of retroviruses contain many common features, including the ubiquitous presence of genes known as gag, pol and env, appearance of fragments of these genes indicate the past action of a retrovirus.

During their reproduction, retroviruses insert their genomes into the DNA of the host cells, and in effect, hijack the host cells' transcription and translation machinery to do the work of building new viruses. The interesting point to note here is that retroviruses are not especially discriminating about where in the genome of the host cell they insert their genetic material. They insert their genetic material into whichever location happens to be conveniently available at the time, and express relatively little preference for any particular segment of the target genome. As a result, retroviral insertions can appear anywhere in a host genome.

Now, the fun part is this. When retroviruses attack germ cells responsible for reproduction, and leave gene fragments behind in those germ cells, those germ cells can then go on to produce sperm and eggs, that pass on those retroviral insertions to future offspring. Over the course of many generations, a species can acquire numerous different retroviral insertions, at different points in the genome, and these insertions are mostly random. Therefore, a retrovirus infecting two different species independently, will almost certainly leave behind retroviral insertions at different places in the genomes of those two species. The probability of those insertions appearing in the same place in the two species, under such conditions, is extremely small. However, if a species acquires retroviral insertions, then diverges and produces two lineages that later become fully-fledged and separate species in their own right, both of those species will inherit the same pattern of retroviral insertions. Therefore, if two species share a common ancestor, one major test that can be performed, consists of searching for retroviral insertions, and seeing if those retroviral insertions line up in the two different species.

When this is performed with the human and chimpanzee genomes, what do we find? We find no less than sixteen retroviral insertions in identical places in the two genomes. This is a finding that ONLY makes sense, if those retroviral insertions were inherited from a common ancestor. The probability of sixteen retroviral insertions appearing independently in two different species via separate infective events is absurdly tiny - taking a figure of 3.5 × 109 base pairs for the size of the human and chimpanzee genomes, the probability of simultaneous identical retroviral insertions via separate infective events is [1/(3.5 ×109)]16, which is 1.97 ×10-153, a pobability so low that one would have to wait a minimum of 10154 years to see such an event happen. On the other hand, if those retroviral insertions were acquired via inheritance from a common ancestor, the probability is precisely 1.

Similar comments apply to pseudogenes (genes that once functioned, but no longer do so), though the mechanism by which these are derived is different from that applicable to retroviral insertions. However, the same pseudogene appearing in the same place in two different lineages, is again strong evidence that the two lineages in question shared a past common ancestor. The classic example in humans and chimpanzees is the GULO pseudogene, which once functioned as the gene coding for the enzyme completing the production of vitamin C. This gene no longer works in either humans or chimpanzees, and lo and behold, the manner in which the gene is broken is the same in humans and chimpanzees. However, a broken GULO pseudogene also appears in guinea pigs, but the manner in which the gene is broken in the guinea pig lineage is different to that seen in humans and chimpanzees, which means that the guinea pig pseudogene was broken independently long after the distant common ancestor of the primate and rodent lineages gave rise to those lineages.

A relevant paper is this one:

Retroviral And Pseudogene Insertion Sites Reveal The Lineage Of Human Salivary And Pancreatic Amylase Genes From A Single Gene During Primate Evolution by Linda C. Samuelson, Karin Weibauer, Claudette M. Snow and Miriam H. Meisler, Molecular and Cellular Biology, 10(6): 2513-2520 (June 1990) [Full paper downloadable from here]

Here's the introduction from the authors:

We have analyzed the junction regions of inserted elements within the human amylase gene complex. This complex contains five genes which are expressed at high levels either in the pancreas or in the parotid gland. The proximal 5'-flanking regions of these genes contain two inserted elements. A γ-actin pseudogene is located at a position 200 base pairs upstream of the first coding exon. All of the amylase genes contain this insert. The subsequent insertion of an endogenous retrovirus interrupted the γ-actin pseudogene within its 3'-untranslated region. Nucleotide sequence analysis of the inserted elements associated with each of the five human amylase genes has revealed a series of molecular events during the recent history of this gene family. The data indicate that the entire gene family was generated during primate evolution from one ancestral gene copy and that the retroviral insertion activated a cryptic promoter.

The above sequence of events is extremely improbable if one assumes that humans and other great apes did not share a common ancestor. On the other hand, the above sequence of events has probability 1 if the great apes did share a common ancestor.

Indeed, the appearance of specific patterns of retroviral insertions shared between different lineages is considered, as a result of the known mechanisms for insertions of retroviral genome fragments into a host lineage, is considered hugely informative with respect to the pattern of common ancestry of those lineages. Here's another paper, which documents the inheritance of a pattern specific to humans and gorillas after the human lineage split from the common ancestor:

Lineage-Specific Expansions Of Retroviral Insertions Within The Genomes Of African Great Apes But Not Humans And Orangutans by Chris T. Yohn, Zhaoshi Jiang, Sean D. McGrath, Karen E. Hayden, Philipp Khaitovich, Matthew E. Johnson, Marla Y. Eichle2, John D. McPherson, Shaying Zhao, Svante Pääbo and Evan E. Eichler, PLoS Biology, 3(4): e110 (2005) [DOI: 10.1371/journal.pbio.0030110, full paper downloadable from here]

Retroviral infections of the germline have the potential to episodically alter gene function and genome structure during the course of evolution. Horizontal transmissions between species have been proposed, but little evidence exists for such events in the human/great ape lineage of evolution. Based on analysis of finished BAC chimpanzee genome sequence, we characterize a retroviral element (Pan troglodytes endogenous retrovirus 1 [PTERV1]) that has become integrated in the germline of African great ape and Old World monkey species but is absent from humans and Asian ape genomes. We unambiguously map 287 retroviral integration sites and determine that approximately 95.8% of the insertions occur at non-orthologous regions between closely related species. Phylogenetic analysis of the endogenous retrovirus reveals that the gorilla and chimpanzee elements share a monophyletic origin with a subset of the Old World monkey retroviral elements, but that the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a significant integration bias against genes, with only 14 of these insertions mapping within intronic regions. Six out of ten of these genes, for which there are expression data, show significant differences in transcript expression between human and chimpanzee. Our data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently, 3–4 million years ago. We speculate on the potential impact of such recent events on the evolution of humans and great apes.

Indeed, the paper on the sequencing of the chimpanzee genome I cited above, cites amongst its findings that the chimpanzee and gorilla lineages acquired new families of retroviral insertions after the chimpanzee/gorilla and human lineages diverged. The above paper merely adds support to that finding. And, lo and behold, the new additions in the chimpanzee/gorilla lineage took place before those two lineages diverged, indicating that the common ancestor of humans and other great apes gave rise to two lineages, one resulting in humans, the other resulting in a common ancestor for chimpanzees and gorillas.

I think that's game over somehow.

But just as you thought you were coming to the end of this, this is just Part 1. I'll post Part 2 in a moment.

[Calilasseia]

Welcome to Part 2.

But just to reinforce the point, there is work on human brain genes that reinforces the hypothesis of common ancestry, the relevant papers being:

Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion by Natalay Kouprina, Adam Pavlicek, Ganeshwaran H. Mochida, Gregory Solomon, William Gersch, Young-Ho Yoon, Randall Collura, Maryellen Ruvolo, J. Carl Barrett, C. Geoffrey Woods, Christopher A. Walsh, Jerzy Jurka and Vladimir Larionov, Public Library of Science Biology, 2(5): e126 (23rd March 2004) [Full paper downloadable from here

Evolution of the Human ASPM Gene, A Major Determinant of Brain Size by Jianzhi Ziang, Genetics, 165: 2063-2070 (December 2003) [Full paper downloadable from here]

Molecular Evolution Of Microcephalin, A Gene Determining Human Brain Size by Yin-Qiu Wang and Bing Su, Human Molecular Genetics, 13(11): 1131-1137 (1st June 2004) [Full paper downloadable from here]

Let's take a look at some of the above work in detail, shall we?

First, the papers on ASPM:

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

So, one of the genes that acts as a determinant of brain size, and as a consequence brain complexity in primates, has been found to have been subject to strong positive selection courtesy of the relevant Ka/Ks ratios (which are used to differentiate between purifying selection, neutral drift and positive selection for any given gene). A gene that plays an important role in human brain development has now been determined to contain within its sequence evidence for positive selection in precisely those areas that are most divergent between primates and other lineages, and the divergence in those areas increases in humans compared to other primates. Moreover, mutations in the human ASPM gene are directly correlated with primary microcephaly, a brain disorder in which the brain size is severely reduced compared to a typical human brain, and in one of those serendipitous correspondences of observed data with evolutionary theory that creationists like to say don't exist, the brain size in individuals exhibiting primary microcephaly is comparable to that of early hominds.

The authors continue as follows:

Introduction

The human brain, particularly the cerebral cortex, has undergone a dramatic increase in its volume during the course of primate evolution, but the underlying molecular mechanisms that caused this expansion are not known. One approach shedding light on the molecular mechanisms of brain evolution is the analysis of the gene mutations that lead to defects in brain development. Among the best examples of such defects is the human primary microcephaly syndrome. Primary microcephaly (MCPH) is an autosomal recessive neurodevelopmental disorder in which the brain fails to achieve normal growth. The affected individuals have severe reduction in brain size; however, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture (McCreary et al. 1996; Mochida and Walsh 2001). Moreover, there are no recognizable abnormalities in the organs other than the central nervous system. The most common cause of MCPH appears to be mutations in the ASPM gene (Roberts et al. 2002).

The ASPM gene encodes a 10,434-bp-long coding sequence (CDS) with 28 exons, and spans 65 kb of genomic DNA at 1q31. ASPM contains four distinguishable regions: a putative N-terminal microtubule-binding domain, a calponin-homology domain, an IQ repeat domain containing multiple IQ repeats (calmodulin-binding motifs), and a C-terminal region (Bond et al. 2002). Though the exact function of the human ASPM in the brain needs to be clarified, the homologue in the fruit fly, Drosophila melanogaster, abnormal spindle (asp), is localized in the mitotic centrosome and is known to be essential for both the organization of the microtubules at the spindle poles and the formation of the central mitotic spindle during mitosis and meiosis. Mutations in asp cause dividing neuroblasts to arrest in metaphase, resulting in reduced central nervous system development (Ripoll et al. 1985; do Carmo Avides et al. 2001; Riparbelli et al. 2001). In the mouse (Mus musculus) brain, the Aspm gene is expressed specifically in the sites of active neurogenesis. Expression in the embryonic brain was found to be greatest in the ventricular zone, which is the site of cerebral cortical neurogenesis (Bond et al. 2002). This expression profile suggests a potential role for Aspm in regulating neurogenesis.

Interspecies comparisons of ASPM orthologs have shown their overall conservation, but also a consistent correlation of greater protein size with larger brain size (Bond et al. 2002). The increase in protein size across species is due mainly to the increased number of IQ repeats, suggesting that specific changes in ASPM may be critical for evolution of the central nervous system.

In an attempt to reconstruct the evolutionary history of the ASPM gene, we isolated large genomic clones containing the entire ASPM gene in several nonhuman primate species. Sequence analysis of these clones revealed a high conservation in both coding and noncoding regions, and showed that evolution of the ASPM gene might have been under positive selection in hominoids. These clones could also provide important reagents for the future study of ASPM gene regulation in its native sequence context.

So, we have a gene that is known to exist in a wide variety of taxa, and in one of those taxa, has been demonstrated experimentally to be responsible for proper development of central nervous system components, with mutations in that gene resulting in reduced central nervous system development because of mitotic arrest in metaphase that takes place in affected central nervous system neuroblasts. Moreover, experimental work has alighted upon no anomalies arising in systems other than the central nervous system as a result of mutations in this gene. So already we have strong evidence that this gene plays a major role in central nervous system development, which is augmented by the finding that mutations in human ASPM are associated with a well understood diagnosable anomaly of brain development.

Moving on, the authors state their results:

Results

Comparison of Genomic Organization of the ASPM Genes in Primates

Homologues from chimpanzee (Pan troglodytes), gorilla ([/i]Gorilla gorilla[/i]), orangutan (Pongo pygmaeus), and rhesus macaque (Macaca mulatta) were isolated by transformation-associated recombination (TAR) cloning in yeast (Saccharomyces cerevisiae), the technique allowing direct isolation of a desirable chromosomal region or gene from a complex genome without constructing its genomic library (Kouprina and Larionov 2003). The method exploits a high level of recombination between homologous DNA sequences during transformation in the yeast. Since up to 15% divergence in DNA sequences does not prevent selective gene isolation by in vivo recombination in yeast (Noskov et al. 2003), for cloning purposes, a TAR vector was designed containing short human ASPM-gene-specific targeting hooks specific to the exon 1 and 39 noncoding regions (see ‘‘Materials and Methods’’). The TAR cloning scheme for isolating the ASPM gene homologues from nonhuman primates is shown in Figure 1. The yield of ASPM-positive clones from chimpanzee, gorilla, orangutan, and rhesus macaque was the same as that from the human DNA, suggesting that most homologous regions from nonhuman primates can be efficiently cloned by in vivo recombination in yeast using targeting hooks developed from human sequences.

We have compared complete gene sequences from primate species with a 65-kb, full-size human ASPM gene. All the analyzed genes are organized into 28 exons encoding a 3,470–3,479-amino-acid-long protein. ASPM genes start with an approximately 800-bp-long CpG island, that harbors promoter sequences, 59 untranslated regions, and the first exon (Figure 2). ASPM sequences share a high degree of conservation (Figure 2H), and pairwise DNA identity ranges from 94.5% for macaque and gorilla to 99.3% for the human–chimpanzee comparison (Table 1). Multiple alignment of the genes revealed a low proportion of indels. Only ten insertions/deletions equal to or longer than 50 bp have been found, all of them located within introns (Figure 2B). Seven detected insertions were mainly associated with repetitive DNA: two (AT)n microsatellite expansions, three Alu insertions, including retroposition of AluYi9 in the orangutan–gorilla–chimpanzee–human clade, and retroposition of a new macaque-specific AluY subfamily similar to human AluYd2. Analysis of eight different macaque individuals showed that this particular insertion is polymorphic in the macaque population (data not shown), and thus the insertion appears to be very recent. One macaque-specific 245-bp-long insertion is linked to expansion of a 49-bp-long, minisatellitelike array. The remaining macaque-specific insertion (50 bp) is nonrepetitive. A closer analysis suggests that the insert is not a processed pseudogene of known genes (data not shown).

Of the two detected deletions, the macaque-specific 72-bp long deletion appears to be associated with nonrepetitve DNA. The second one, an 818-bp-long deletion in orangutan, was probably caused by homologous Alu–Alu recombination (see below and Figure S1). The remaining indels are related to expansion/contraction of a short minisatellite array. It was caused either by a 53-bp expansion in the gorilla–chimpanzee–human clade or by two independent deletions/contractions in the macaque and orangutan lineages.

An approximately 3-kb-long intronic segment between exons 4 and 5 is present in several copies in the genome (Figure 2E; Figure S2). Closer analysis of the human genome confirmed that copies of this region are homologous to 24 segmental duplications located mainly in telomeric regions of Chromosomes 1–8, 10, 11, 16, 19, 20, and Y. Based on the sequence similarity and the presence of an L1P4 LINE insertion at the 5' end, the most closely related are three duplications at 7q11–13. The most similar copy is located on Chromosome 7 and shares 93% identity with the ASPM intronic segment. Five duplications are located on Chromosome 1; the closest copy is found 27 Mb away from the ASPM gene.

We looked for several common motifs associated with genomic breakpoints in cancers (Abeysinghe et al. 2003). Figure 2F shows the positions of such potentially unstable oligonucleotides. Interestingly, the orangutan-specific deletion (Figure 2B) has its 5' breakpoint located just 1 bp upstream of a sequence 100% identical to the chi-like consensus motif GCWGGWGG (see Figure S1). The chi motif is recognized by the RecBCD-mediated recombination pathway in prokaryotes and seems to be associated with rearrangements in the human genome (Dewyse and Bradley 1991; Chuzhanova et al. 2003). Both deletion breakpoints in the orangutan deletion are located within 5' parts of two Alu sequences, suggesting that the deletion was created by homologous Alu–Alu recombination. Similar homologous recombinations with breakpoints located near chi-like motifs in 5' regions of Alu sequences were described previously (Chen et al. 1989; Rudiger et al. 1995).

In summary, despite the presence of a few indels, coding and noncoding regions of ASPM homologues show a marked degree of conservation.

Note how differences between human/chimpanzee and other primate lineages, when located, are accompanied by specification of appropriate mechanisms for the generation of those differences in the respective lineages, and whilst the exact mechanism applicable remains to be determined in some cases, the fact that the observed data are consistent with known mutational mechanisms once again reinforces our confidence in the results.

The authors move on to state the following:

Evolution of the ASPM Protein

We have analyzed ASPM CDSs from six primate species: human, chimpanzee, gorilla, orangutan, rhesus macaque, and African green monkey (Cercopithecus aethiops). Except for orangutan and rhesus macaque, two or more ASPM CDSs were used for analysis. ASPM proteins showed the same overall length and domain structure (Figure 3A). The IQ repeat domain contains the same number of repeats, suggesting that their expansion occurred in early primate evolution. The CDSs are, as expected, more conserved than the complete gene sequences with promoter and intronic regions (Table 2; Table 3). Only six short indels were identified (Figure 3B).

From the DNA and protein conservation profiles (Figure 3I), ASPM segments evolve differently along the length of the CDS. N- and C-terminal regions and the region corresponding to exons 5–15 are conserved. In contrast, exons 3 and 4 and the complete IQ repeat domain (positions 1,267–3,225) are more variable. Indeed, nonsynonymous substitutions in hominoid primates (Figure 3C) and in ancestral lineages (Figure 3D) and nonsynonymous polymorphism (Figure 3E) are nearly absent in the conserved central (exons 5–15) and C-terminal regions. This pattern indicates different rates of evolution along the ASPM protein, visualized by plots of synonymous Ks and nonsynonymous Ka rates (Figure 3H) and supported by phylogenetic analysis (see below and Figure 4). It is notable that the comparison of the primate and mouse proteins also revealed the same pattern of conservative and nonconservative regions along ASPM protein (Figure S3).

Analysis of the nonsynonymous/synonymous substitution ratio (x = Ka/Ks) revealed an elevated value in the human branch (Figure 4A). According to the likelihood ratio test, the human x rate is significantly different from the rate in the rest of the tree (p < 0.05). Also the model that the complete gorilla–chimpanzee–human clade is evolving at one x rate different from that in the rest of the tree is well supported (p < 0.01). Because ASPM consists of regions with different degrees of sequence conservation (see Figure 3), we separately analyzed a conserved region (exons 5–15 plus a small part of exon 16) and a variable IQ repeat domain. As can be seen (Figure 4B) the conserved region has all branches shorter, indicating overall a slower rate of evolution. In the human lineage, the x ratio equals zero; however, the test for whether the human branch has a different (lower) x rate than the rest did not yield significant values. In contrast, the tree based on the variable IQ repeat domain exhibits x values greater than one for the human and gorilla branches (Figure 4C). The likelihood ratio test supports the model in which human and gorilla lineages evolved under a significantly higher x ratio than the rest of the tree. Similar results were obtained for exon 18 with additional sequences from two New World monkeys (Figure 4D). As seen from Figure 4A–4D, different sequences from African green monkey, gorilla, and chimpanzee individuals result in different x values for their corresponding terminal branches. One chimpanzee sequence also produced an x ratio greater than one for exon 18 (Figure 4D). It is worth noting that neither codon bias nor selection on third codon positions seemed to influence the synonymous rate Ks strongly (Table S1). Therefore, the high Ka/Ks ratios in human and gorilla are likely to be products of adaptive evolution.

Sequencing of two CDSs in African green monkey, three in gorilla, and three in chimpanzee allowed us to look for ASPM polymorphism in those species (see Figure 3E). Human polymorphism data from ASPM mutant haplotypes are not representative of wild-type variation so were not used in these comparisons. For African green monkey, five synonymous and five nonsynonymous changes were found between two sequences. The gorilla and chimpanzee CDSs in particular showed an apparently high degree of replacement polymorphism. Gorilla polymorphism included 35 point mutations (15 silent mutations and 21 replacements). Chimpanzee sequences differed in five synonymous and 11 nonsynonymous sites. In order to interpret this seemingly high level of observed polymorphism, intraspecific diversity was compared to interspecific diversity using the McDonald and Kreitman test (McDonald and Kreitman 1991). In the case of chimpanzee polymorphism compared to divergence with human, we could not reject the null hypothesis that polymorphism and divergence between species were significantly different (William’s adjusted G statistic = 0.083, chi-square with 1 d.f., not significant; values based on PAML-generated Ka and Ks values using the free ratio model). Gorilla polymorphism was compared to divergence between the gorilla common ancestor and the human–chimpanzee common ancestor. In this case we can reject the null hypothesis (William’s adjusted G statistic = 122.45, chi-square with 1 d.f., p < 0.001) to conclude that the pattern of gorilla polymorphism is therefore different from the divergence pattern. Indeed gorilla polymorphism is less than variation resulting from divergence: within species, the x ratio is 1.43 for gorillas compared to 2.2 for the divergence between the gorilla common ancestor and the human–chimpanzee common ancestor. Intraspecific variation, although seemingly unusual in showing so many replacement substitutions in both chimpanzee and gorilla, is less than or in line with what we have observed for ASPM divergence between species. Therefore, relaxation of selection cannot explain the high nonsynonymous/synonymous substitution ratios among African hominoids, further supporting the idea that adaptation has occurred in ASPM.

For those unfamiliar with Ka/Ks ratios, Ks is the number of synonymous mutations. These are mutations that result in a codon that codes for the same amino acid as the codon that existed prior to mutation - for example, the codons ATT and ATC both code for the amino acid isoleucine, so a change from an ATT codon to an ATC codon is a synonymous mutation. Ka is the number of non-synonymous mutations, for example a change from ATT (coding for isoleucine) to ATG (which codes for methionine, and also acts as a start codon). If the ratio Ka/Ks is less than one, then the gene in question is subject to purifying selection (in other words, most mutations in this gene are selected against because they are deleterious). If the Ka/Ks ratio is very close to 1, then the gene is subject to neutral drift. If the Ka/Ks ratio is greater than one, then the gene is subject to positive selection (mutations in the gene that have occurred have been beneficial and thus disseminated to future generations). The important tests performed upon the ASPM gene yield Ka/Ks ratios greater than one in those primate lineages closest to humans, with the human ASPM gene possessing the largest Ka/Ks ratio, indicating that positive selection took place on the ASPM gene leading to an increase in brain size.

Let's catch up with the authors again in the discussion section:

Discussion

In this study, we applied TAR cloning technology to investigate molecular evolution of the ASPM gene, which is involved in determining the size of the human brain and in which mutations lead to MCPH. The ASPM homologue in the fruit fly is essential for spindle function, suggesting a role for this gene in normal mitotic divisions of embryonic neuroblasts. Complete gene homologues from five primate species were isolated and sequenced. In agreement with the predicted critical role of ASPM in brain development, both coding and noncoding regions of ASPM homologues showed a marked degree of conservation in humans, other hominoids, and Old World monkeys. The differences found in noncoding regions were small insertions/deletions and lineage-specific insertions of evolutionarily young Alu elements into introns.

Analysis of nonsynonymous/synonymous substitution ratios indicates different rates of evolution along the ASPM protein: part of ASPM evolved under positive selection while other parts were under negative (purifying) selection in human and African ape lineages. Such ‘‘mosaic’’ selection has been previously described for other proteins (Endo et al. 1996; Crandall et al. 1999; Hughes 1999; Kreitman and Comeron 1999). When our work was completed, the paper by Zhang supporting accelerated evolution of the human ASPM was issued (Zhang 2003). However, because the author did not analyze the gorilla gene homologue, he concluded that accelerated sequence evolution is specific to the hominid lineage. Our finding that selection on ASPM begins well before brain expansion suggests that the molecular evolution of ASPM in hominoids may indeed be an example of a molecular ‘‘exaptation’’ (Gould and Vrba 1982), in that the originally selected function of ASPM was for something other than large brain size.

In the case of ASPM, rapidly evolving residues are mainly concentrated in the IQ repeat domain containing multiple IQ motifs, which are calmodulin-binding consensus sequences. While there is no direct evidence yet, it is likely that the function of human ASPM is modulated through calmodulin or calmodulinlike protein(s). Previous interspecies comparisons of ASPM proteins have shown a consistent correlation of greater protein size with larger brain size mainly because of the number of IQ repeats (Bond et al. 2002). For example, the asp homologue of the nematode Caenorhabditis elegans contains two IQ repeats, the fruit fly—24 IQ repeats, and the mouse—61 IQ repeats, and there are 74 IQ repeats in humans (Bond et al. 2002). ASPM homologues in the nonhuman primates examined here contain the same number of IQ repeats as human, supporting the idea that repeat expansion occurred prior to the anthropoid divergence (which gave rise to New World monkeys, Old World monkeys, and hominoids) and possibly even earlier in primate evolution. IQ motifs are seen in a wide variety of proteins, but the ASPM proteins in primates are unique, because they have the largest known number of IQ repeats. Given the proposed role of ASPM in regulating divisions of neuronal progenitors, both the number of repeats and the particular amino acid substitutions in the IQ repeats may be strongly related to brain evolution.

Human ASPM gene mutations which lead to MCPH provide a direct link between genotype and phenotype. ASPM is yet another example on the growing list of positively selected genes that show both accelerated evolution along the human lineage and involvement in simple Mendelian disorders (Clark et al 2003). However, ASPM is unique because its distinctive pattern of accelerated protein evolution begins several million years prior to brain expansion in the hominid lineage. Absolute brain size in orangutans (430 g in males; 370 g in females) is barely different from that in gorillas (530 g in males; 460 g in females) and common chimpanzees (400 g in males; 370 g in females) (Tobias 1971), yet accelerated ASPM evolution began in the common ancestor of gorillas, chimpanzees, and humans, approximately 7–8 million years ago. Only much later did brain expansion begin in hominids, starting at 400–450 g roughly 2–2.5 million years ago and growing to its final current size of 1350–1450 g approximately 200,000–400,000 years ago (Wood and Collard 1999). Therefore genotypic changes in ASPM preceded marked phenotypic changes in hominoid brain evolution, at least at the level at which they have currently been studied. The molecular changes in ASPM may predict the existence of differences in early neurogenesis between orangutans, on the one hand, and gorillas, chimpanzees, and humans, on the other, which may manifest as more subtle differences in brain anatomy than gross changes in brain volume.

How might evolutionary changes in the ASPM protein affect cerebral cortical size? One potential mechanism might be that changes in ASPM induce changes in the orientation of the mitotic spindle of neuroblasts. Normally, neural precursor cells can have mitotic spindles oriented parallel to the ventricle or perpendicular to the ventricle. Mitoses in which daughter cells are oriented next to one another at the ventricular zone are typically ‘‘symmetric’’ in that a single progenitor cell generates two progenitor cells, causing exponential expansion of the progenitor pool. In contrast, mitoses that generate daughter cells that are vertically arranged are typically ‘‘asymmetric’’ so that one daughter cell becomes a postmitotic neuron, whereas the other daughter cell remains as a progenitor, causing only a linear increase in cell number. Control of this proliferative symmetry can cause dramatic alterations in cerebral cortical size (Chenn and Walsh 2002), and so changes in ASPM could regulate cortical size by making subtle changes in spindle orientation. Alternatively, evolutionary changes in ASPM may not themselves have led to increase in the size of the brain, but instead perhaps ASPM might be essential to insure faithful DNA replication and proper chromosome segregation. In rodents, a surprising number of cerebral cortical neurons are aneuploid (Rehen et al. 2001). Perhaps directed selection of specific domains of ASPM helps insure faithful chromosome segregation to allow a larger number of cerebral cortical neurons to be formed without an unduly high incidence of chromosome aneuploidy.

Functional genomics studies are clearly needed to elucidate the exact nature of the molecular mechanisms affected by ASPM gene evolution in hominoids. Here, we have demonstrated the utility of TAR cloning for evolutionary sequence comparisons among humans and other primates. In addition, the ASPM TAR clones isolated in these studies could provide valuable reagents for studying ASPM gene regulation in its natural sequence context. Overall, we anticipate this technology will be extremely useful in studying the evolution of other genes that may be responsible for uniquely human traits.

Note

The related paper by Evans et al. (2004) was published in Human Molecular Genetics shortly after this paper was submitted.

So, not only has a correlation between ASPM and human brain evolution been established, but a possible mechanism by which it affects brain size, courtesy of the orientation of the mitotic spindle in dividing brain cells, has been proposed, and will doubtless be the subject of further research in order to confirm or refute the hypothesis with respect to the known mitotic spindle role that this gene plays.

Moving on, let's now look at the other ASPM paper:

ABSTRACT

The size of human brain tripled over a period of ~2 million years (MY) that ended 0.2–0.4 MY ago. This evolutionary expansion is believed to be important to the emergence of human language and other high-order cognitive functions, yet its genetic basis remains unknown. An evolutionary analysis of genes controlling brain development may shed light on it. ASPM (abnormal spindle-like microcephaly associated) is one of such genes, as nonsense mutations lead to primary microcephaly, a human disease characterized by a 70% reduction in brain size. Here I provide evidence suggesting that human ASPM went through an episode of accelerated sequence evolution by positive Darwinian selection after the split of humans and chimpanzees but before the separation of modern non-Africans from Africans. Because positive selection acts on a gene only when the gene function is altered and the organismal fitness is increased, my results suggest that adaptive functional modifications occurred in human ASPM and that it may be a major genetic component underlying the evolution of the human brain.

And, appositely enough, the Kouprina et al paper cites this paper by Ziang in its list of references as one of the supporting papers providing additional confirmation of the results.

Ziang continues with:

AMONG mammals, humans have an exceptionally big brain relative to their body size. For example, in comparison with chimpanzees, the brain weight of humans is 250% greater while the body is only 20% heavier (McHenry 1994). The dramatic evolutionary expansion of the human brain started from an average brain weight of 400–450 g ~2–2.5 million years (MY) ago and ended with a weight of ~1350–1450 g ~0.2–0.4 MY ago (McHenry 1994; Wood and Collard 1999). This process represents one of the most rapid morphological changes in evolution. It is generally believed that the brain expansion set the stage for the emergence of human language and other high-order cognitive functions and that it was caused by adaptive selection (Decan 1992), yet the genetic basis of the expansion remains elusive. A study of human mutations that result in unusally small brains may help identify the genetic modifications that contributed to the human brain expansion. In this regard, primary microcephaly (small head) is of particular interest (Mochida and Walsh 2001; Bond et al. 2002; Kumar et al. 2002). Microcephaly is an autosomal recessive genetic disease with an incidence of 4–40 per million live births in western countries (Mochida and Walsh 2001; Kumar et al. 2002). It is defined as a head circumference >3 standard deviations below the population age-related mean, but with no associated malfunctions other than mild-to-moderate mental retardation (Mochida and Walsh 2001; Kumar et al. 2002).

The reduction in head circumference correlates with a markedly reduced brain size. Microcephaly is genetically heterogeneous, associated with mutations in at least five loci (Mochida and Walsh 2001; Kumar et al. 2002), one of which was recently identified and named ASPM (abnormal spindle-like microcephaly associated; Bond et al. 2002). Four different homozygous mutations in ASPM introducing premature stop codons were found to cosegregate with the disease in four respective families, while none of these mutations were found in 200 normal human chromosomes (Bond et al. 2002). Because the brain size of a typical microcephaly patient (430 g; Mochida and Walsh 2001; Kumar et al. 2002) is comparable with those of early hominids such as the 2.3- to 3.0-MY-old Australopithecus africanus (420 g; McHenry 1994; Wood and Collard 1999), I hypothesize that ASPM may be one of the genetic components underlying the human brain expansion. Signatures of accelerated evolution of ASPM under positive selection during human origins would strongly support my hypothesis, because the action of positive selection indicates a modification in gene function resulting in elevated organismal fitness (Zhang et al. 2002). Below I provide population genetic and molecular evolutionary evidence for the operation of such adaptive selection on ASPM.

So, let's look at the results, shall we?

RESULTS

Elevation of dN/dS in the human ASPM lineage:

Human ASPM has 28 coding exons, spanning 62 kb in chromosome 1p31 and encoding a huge protein of 3477 amino acids (Figure 1). I determined the entire coding sequences of ASPM from one human, one chimpanzee, and one orangutan, and compared them in the phylogenetic tree of the three species (Figure 2). The orangutan sequence is used as the outgroup for humans and chimpanzees so that nucleotide substitutions on the human and chimpanzee lineages can be separated. I did not sequence the gorilla because the gorilla sequence may not be appropriate as the outgroup due to incomplete lineage sorting (Satta et al. 2000). Use of orangutan, a slightly more distant outgroup, solves this problem. A commonly used indicator of natural selection at the DNA sequence level is the ratio of the rate of nonsynonymous nucleotide substitution (dN) to that of synonymous substitution (dS). Most functional genes show dN/dS < 1, because a substantial proportion of nonsynonymous mutations are deleterious and are removed by purifying selection, whereas synonymous mutations are more or less neutral and are generally uninfluenced by selection. A gene may occasionally exhibit dN/dS > 1 when a large fraction of nonsynonymous mutations are advantageous and are driven to fixation by positive selection (Li 1997; Nei and Kumar 2000). I estimated the dN/dS ratio for ASPM in each of the three tree branches (Figure 2), using a maximum-likelihood method, and found that dN/dS is lowest in the orangutan branch (0.43), higher in the chimpanzee branch (0.66), and highest in the human branch (1.03). The hypothesis of dN/dS = 1 is rejected for the orangutan branch (P < 0.001, likelihood-ratio test), but not for the other two branches, suggesting a difference in selection has occurred. Indeed, a test of the difference in dN/dS between the human and orangutan branches gives a marginally significant result (P = 0.064), but the difference between the chimpanzee and orangutan branches is not significant (P = 0.29), nor is the difference between human and chimpanzee branches (P = 0.45). Because the dN/dS ratio between the orangutan and mouse (Mus musculus) is also low (0.29), an increase of dN/dS in humans is more likely than a decrease in orangutans. The mouse sequence (GenBank accession no. AF533752) was not included in the phylogeny-based analysis as it is relatively distantly related to the ape sequences and contains multiple insertions and deletions, which would make the inference less reliable. Similar results are obtained when I first infer the ASPM sequence for the common ancestor of humans and chimpanzees and then estimate the dN/dS ratio by counting the numbers of synonymous and non- synonymous nucleotide substitutions on each branch. For instance, this approach gives dN/dS = 1.13, 0.84, and 0.52, respectively, for the human, chimpanzee, and orangutan branches.

Complete functional relaxation does not adequately explain the elevation of dN/dS:

Two hypotheses may explain the increase in dN/dS to 1.03 during the evolution of human ASPM. First, the functional constraints and purifying selection on ASPM may have been completely relaxed and many deleterious nonsynonymous mutations were fixed by random genetic drift. Alternatively, advantageous nonsynonymous substitutions under positive selection occurred at some sites, while purifying selection acted at some other sites, resulting in an average dN/dS of ~ 1. Under the first hypothesis, ASPM has been under pure neutral evolution since the human-chimpanzee separation ~6–7 MY ago (Brunet et al. 2002). Using rates of single-nucleotide mutations and insertion/deletion mutations estimated from human-chimpanzee genomic comparisons (Britten 2002; Yi et al. 2002), I conducted a computer simulation of neutral evolution of ASPM (see materials and methods). I found that the probability that ASPM retains its open reading frame after 6 MY of neutral evolution is extremely low (1.7 × 10-4). Even when the above two mutation rates are both halved, the probability is still very small (0.014), suggesting that ASPM must have been under purifying selection. The fact that nonsense mutations in ASPM lead to microcephaly also demonstrates the presence of functional constraints on the gene. Thus, the hypothesis of complete relaxation of functional constraints and lack of purifying selection for the past 6–7 MY of human evolution is inconsistent with the data, and some sites in ASPM must have been subject to purifying selection (dN/dS < 1). This result would imply, although not prove, that some other sites are under positive selection (dN/dS > 1), so that the average dN/dS across the entire protein is ~1. However, it is difficult to rule out the possibility of an incomplete functional relaxation in human ASPM, which can lead to a dN/dS ratio of ~1 when the number of substitutions is relatively small. A population genetic study may help resolve this question.

Signatures of purifying selection from population genetic data:

The entire coding sequence of ASPM is determined from 14 human individuals of different geographic origins. A total of 33 single-nucleotide polymorphisms are found (Tables 1 and 2). The derived and ancestral alleles are inferred using the chimpanzee and orangutan sequences as outgroups. Tajima’s (1989) and Fu and Li’s (1993) tests reveal slight departure of the data from the Wright-Fisher model of neutrality (D = -1.29, P =0.081; F = -1.76, P = 0.074; Table 2). But Fay and Wu’s (2000) test, which is designed to detect recent selective sweeps, does not show a significant result (H = -2.08, P = 0.21). Thus, the negative D and F likely reflect recent population expansions and/or purifying background selection. A recent study suggested that negative D values may also be found under certain sampling schemes if there is fine-scale population differentiation (Ptak and Przeworski 2002). When the synonymous and nonsynonymous sites were analyzed separately, I detected significant negative D and F values at nonsynonymous sites (P < 0.05; Table 2), but not at synonymous sites. H is not significant at either type of site. These results suggest that the nonsynonymous sites in human ASPM are subject to purifying selection. It should be mentioned that the recombination rate in the ASPM region is ~1.8 cM/106 nucleotides (Kong et al. 2002), which translates into 1.1 × 10-3 recombination/meiosis for the sequences analyzed here. This relatively high recombination rate localizes signatures of selection to a small region surrounding the selected sites. This might in part explain the above differences in the test results between synonymous and nonsynonymous sites.

Population genetic theory predicts that deleterious mutations do not reach high frequencies in populations, while neutral and advantageous mutations do. A comparison between rare and common polymorphisms may detect purifying selection of deleterious mutations (Fay et al. 2001). Fay et al. recommended a frequency of ~10% for the derived allele as a cutoff between rare and common polymorphisms (Fay et al. 2001, 2002). In the present sample of 28 chromosomes, derived alleles that appear one or two times are regarded as rare polymorphisms, and the rest are common. Because of the limited sample size, a truly rare allele may inadvertently appear more than twice in our sample and a truly common allele may inadvertently be regarded as rare. Using probability theory, I computed that the probability of the former error is <5% for an allele with frequency <3% and the probability of the latter error is <5% for an allele with frequency >20%. Thus, the present classification of rare and common alleles is expected to be relatively accurate. I observed that nR =15 nonsynonymous and sR = 5 synonymous rare polymorphisms and nC = 5 nonsynonymous and sC = 8 synonymous common polymorphisms from the present data (Table 2; Figure 1). The ratio of nC to nR (5/15 = 0.333) is significantly lower than that of sC to sR (8/5 = 1.6; [cvhr]967[/chr]2 = 4.41, P < 0.05; Table 2). Since synonymous mutations are more or less neutral, the observed deficit of common nonsynonymous polymorphisms suggests that purifying selection has prevented the spread of nonsynonymous deleterious mutations. It is estimated by the likelihood method that there areN=7459 and S=2972 potentially nonsynonymous and synonymous sites in ASPM, respectively. Thus, for rare polymorphisms, there are nR/N = 15/7459 = 2.01 × 10-3 polymorphisms/nonsynonymous site and sR/S = 5/2972 = 1.68 × 10-3/synonymous site. Their difference is statistically insignificant (χ2 = 0.09, P > 0.5). In contrast, for common polymorphisms, the number is significantly smaller per nonsynonymous site (nC/N = 5/7459 = 0.67 × 10-3) than per synonymous site (sC/S = 8/2972 = 2.69 × 10-3; χ2 = 6.98, P < 0.01), confirming that purifying selection has reduced the number of common nonsynonymous polymorphisms. This result also suggests the absence or rareness of advantageous nonsynonymous polymorphisms of ASPM that are currently segregating in humans, as such polymorphisms would predominantly show up as common polymorphisms and render nC/N higher. This is consistent with the above result from Fay and Wu’s test. The proportion of nonsynonymous polymorphisms not under purifying selection may be estimated by (nC/N)/(sC/S) = (0.67 × 10-3)/(2.69 × 10-3) = 0.25 or by (nC/sC)/(nR/sR) = (5/8)/(15/5) = 0.21. The two estimates are close to each other and to the dN/dS ratio between the mouse and orangutan (0.29). This indicates that human ASPM is currently under relatively strong purifying selection, and the strength of selection is comparable to or even greater than that in the long-term evolution of mammalian ASPM.

Comparison of polymorphism and divergence suggests past positive selection:

Because both the synonymous and nonsynonymous common polymorphisms are largely neutral, comparing them with the fixed substitutions between humans and chimpanzees can reveal the signature of selection that has influenced the substitution processes (McDonald and Kreitman 1991; Fay et al. 2001, 2002; Smith and Eyre-Walker 2002). This comparison shows a significant excess of fixed nonsynonymous substitutions (χ2 = 3.88, P < 0.05, Table 2), suggesting that some nonsynonymous substitutions were fixed by positive selection. Because the expansion of brain size occurred in the human lineage after the human-chimpanzee split, it is more relevant to examine whether the human branch exhibits an excess of nonsynonymous substitutions. For this, the ASPM sequence of the common ancestor of humans and chimpanzees was inferred by the Bayesian method. Because the sequences considered are closely related, this inference is reliable, with the average posterior probability >0.999. Comparing the ancestral sequence with the polymorphic human sequences, I identified 16 nonsynonymous and 6 synonymous mutations that have been fixed in the human lineage (Table 2; Figure 1). Their ratio (16/6 = 2.67) is significantly greater than that for common polymorphisms (nC/sC = 5/8 = 0.63; χ2 = 4.00, P < 0.05). The number of neutral nonsynonymous substitutions may be estimated from the number of synonymous substitutions multiplied by nC/sC, which yielded 6 × (5/8) = 3.75 (Fay et al. 2001, 2002; Smith and Eyre-Walker 2002). The number of nonsynonymous substitutions unexplainable by neutral evolution is 16 - 3.75 = 12, which may have been fixed by positive selection. It should be noted that a recent population expansion can cause an overestimate of the number of adaptive substitutions when slightly deleterious mutations are present. However, such overestimation is unlikely in the present case because the current effective population size of humans, even after the recent expansion, is still smaller than the long-term effective population size separating humans and chimpanzees and the effective population size of the common ancestor of humans and chimpanzees (Takahata et al. 1995; Chen and Li 2001; Kaessmann et al. 2001; Eyre-Walker 2002). It is interesting that there is no significant excess of nonsynonymous substitutions for either the chimpanzee or orangutan branches when the common polymorphisms and substitutions are compared (P > 0.05).

IQ repeats and brain size variation:

Human ASPM contains multiple calmodulin-binding IQ repeats (Bond et al. 2002). In a comparison of putative orthologous ASPM genes from the human, mouse, fruit fly (Drosophila melanogaster), and nematode (Caenorhabditis elegans), Bond et al. (2002) noticed that organisms with larger brains have more IQ repeats, implying a possible relation of IQ repeats and brain size. In particular, the predominant difference between the human and mouse ASPM genes is a large IQ-repeat-encoding insertion of 867 nucleotides at the end of exon 18. However, my data showed no difference in the number of IQ repeats between human and chimpanzee ASPM sequences. To trace the origin of the large insertion in human ASPM, I amplified and sequenced from several mammals two DNA segments that cover most of the insertion (Figure 1). Segment I is of 212 nucleotides and segment II is of 706 nucleotides. One or both segments were obtained from species belonging to primates, Cetartiodactyla, Carnivora, and Hyracoidea, but not from mouse or hamster (Figure 3). Phylogenetic analyses were conducted to confirm that the obtained sequences are orthologous to the human sequence (Figure 4). While nonamplification of a sequence does not prove its nonexistence, the amplification of the orthologous sequence indicates its presence. From the recently established mammalian phylogeny (Murphy et al. 2001), it can be inferred that the large human insertion was already present in the common ancestor of most placental mammals, but was deleted in mouse and possibly in other rodents (Figure 3). Thus, this IQ-repeat-containing sequence does not explain the brain size variation among many nonrodent mammals.

Yes, a lot of statistical work in there. Basically, the above is a fairly involved calculation intended to extract from the data the likely number of sites that were subject to purifying selection, and the number likely to have been subject to positive selection, with a view to elucidating which sites were subject in each case to each selection process, then comparing that theoretical calculation with the observed data in order to verify the robustness of the underlying theory.

Now, at last, the discussion section!

DISCUSSION

In the above, I provided evidence that advantageous amino acid substitutions unrelated to IQ repeats have been fixed by adaptive selection in human ASPM after the human-chimpanzee split, which strongly suggests that ASPM might be an important genetic component in the evolutionary expansion of human brain. The episode of positive selection on ASPM appears to have ended some time ago, as there is no evidence for positive selection on ASPM in current human populations; rather, relatively strong purifying selection is detected. Roughly, selective sweeps occurring in the past 0.5N generations may be detected (Fay and Wu 2000), where N is the effective population size of humans and is thought to be ~10,000 (Takahata et al. 1995; Harpending et al. 1998). That is, the positive selection detected in ASPM occurred some time between 6–7 and 0.1 MY ago (0.5 × 10,000 generations × 20 years/generation). The latter date coincides with the suggested time of migration of modern humans out of Africa (reviewed in Cavalli-Sforza and Feldman 2003). It is also interesting to note that although the precise time when positive selection acted on ASPM is difficult to pinpoint, my estimate is consistent with the current understanding that the human brain expansion took place between 2–2.5 and 0.2–0.4 MY ago (McHenry 1994; Wood and Collard 1999). Furthermore, a selective sweep in human FOXP2, a gene involved in speech and language development, has been detected (Enard et al. 2002; Zhang et al. 2002). This sweep was estimated to have occurred no earlier than 0.1–0.2 MY ago (Enard et al. 2002; Zhang et al. 2002). That is, the adaptive evolution of FOXP2 postdated that of ASPM, consistent with the common belief that a big brain may be a prerequisite for language (Decan 1992).

Studies of ASPM in model organisms can help us understand how it impacts brain size. The mouse Aspm is highly expressed in the embryonic brain, particularly during cerebral cortical neurogenesis (Bond et al. 2002). The fruit fly ortholog asp is involved in organizing and binding together microtubules at the spindle poles and in forming the central mitotic spindle (Gonzalez et al. 1990; Wakefield et al. 2001). Mutations in asp cause dividing neuroblasts to arrest in metaphase, resulting in reduced central nervous system development (Wakefield et al. 2001). The amino acid substitutions in human ASPM are located in exons 3, 18, 20, 21, and 22 (Figure 1), which encode a putative microtubule-binding domain and an IQ calmodulin-binding domain (Bond et al. 2002). These features suggest that the adaptive substitutions in human ASPM might be related to the regulation of mitosis in the nervous system, which can be tested in the future by functional assays of human ASPM as well as a laboratory-reconstructed ASPM protein of the common ancestor of humans and chimpanzees.

Oh look. Ziang mentions one of the other papers in my above list of citations, namely the Enard et al paper on FOXP2! Another one of those serendipitous happenstances.

Basically, Ziang presents evidence that ASPM mutations were positively selected for at an early stage in human evolution, which then led to brain expansion, and this was then followed by mutations in FOXP2 facilitating language development (more on this in a moment!).

I'll leave the microcephalin paper to one side at this juncture, except to quote the abstract (I can provide the full paper via E-Mail to anyone who wants it):

Microcephalin gene is one of the major players in regulating human brain development. It was reported that truncated mutations in this gene can cause primary microcephaly in humans with a brain size comparable with that of early hominids. We studied the molecular evolution of microcephalin by sequencing the coding region of microcephalin gene in humans and 12 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results showed that microcephalin is highly polymorphic in human populations. We observed 22 substitutions in the coding region of microcephalin gene in human populations, with 15 of them causing amino acid changes. The neutrality tests and phylogenetic analysis indicated that the rich sequence variations of microcephalin in humans are likely caused by the combination of recent population expansion and Darwinian positive selection. The synonymous/non-synonymous analyses in primates revealed positive selection on microcephalin during the origin of the last common ancestor of humans and great apes, which coincides with the drastic brain enlargement from lesser apes to great apes. The codon-based neutrality test also indicated the signal of positive selection on five individual amino acid sites of microcephalin, which may contribute to brain enlargement during primate evolution and human origin.

So, ASPM and microcephalin apparently act as a genetic tag team in human brain development, and mutations in either are associated with microcephaly-class conditions. Interesting.

Basically, analysis of the genomes of humans and chimpanzees has established that the ASPM gene underwent accelerated evolution in the human lineage, after divergence from the common ancestor, and moreover, that mutations in the human ASPM gene result in a condition known as primary microcephaly, which results in humans inheriting the mutant gene developing a brain whose size is comparable to that of the chimpanzee. I contend that anyone who chooses to dismiss this as mere coincidence, needs to re-take basic science classes.

Game over.

At least admit that it's theoretical

Wrong. The evidence is above. Read it.

and that you 'think' that this is how humans evolve. Why the need to harp on about it as if it's a fact?

Because it is a fact. Read the above and find out why.

[campermon]

!

MODNOTE Questioner121 This post and this post contain inflammatory content. and This post and this post contain preaching. As this is your 3rd warning for personal attack / infammatory behaviour you have earned yourself a one week suspension. On your return to the community I suggest a close reading of Forum Users Agreement, reproduced below. For your convenience, I have bolded the sections relevant to this warning, but don't let that put you off reading the FUA in its entirety: [Reveal] Spoiler: relevant section of the Forum User's Agreement Membership Agreement for rationalskepticism.org Members of rationalskepticism.org agree to: 1.1 only register one account with rationalskepticism.org and not allow anyone else to use your account. 1.2. not cause harm or disruption to the forum or other members, for example please don't: a. post criminal content b. post racist, sexist, homophobic content (and no Holocaust denial) c. post personal attacks or insults towards other members d. i. start threads outside of Feedback that are critical of the forum habits and/or behaviours of another member d. ii. start threads that discuss the opinions, positions and/or arguments of another member without permission from that member e. attempt to inflame or provoke another member(s) f. post multiple copies of your posts g. try to take threads off-topic h. post personal information about another member(s) i. share Private Messages (PMs) without the member’s permission. j. send harrassing PMs to any other member(s) k. edit your posts substantially if others have responded to them. m. quote mine, plagiarise, or otherwise misrepresent information n. post about disruptive actions against external sites o. quote another member in your signature or on your profile without their permission. p. post, or offer to post, on behalf of members who have been banned or suspended. 1.3. not discuss personal sexual issues and not post (or link to) anything pornographic 1.4. use NSFW tags and appropriate warnings for anything that is not suitable for all ages or for viewing at work 1.5. not preach 1.6. not spam or solicit 1.7. accept and follow the directions outlined in Appendix 3. Legal and Other Issues. Please Note: Additional explanations for clauses 1.1 to 1.6 can be found in Appendix 1. Membership Agreement - Explanatory Notes. Information about how the forum is moderated, including the consequences for breaching this agreement can be found in Appendix 2 - Forum moderation. The previous Forum User's Agreement is Appendix 4. Please do not discuss this issue in this thread. If you wish to discuss this further then you can PM myself or any of the other moderators. Campermon

[campermon]

!

GENERAL MODNOTE Advice to all posters I know that the majority of you don't need this advice (he says whilst reading through yet more reports from this thread), but I'm going to give it anyway. Let's remember that this is the creationism forum. Considering the nature of the topics herein, you will find posters presenting ideas that will conflict with the scientific view of the nature. In responding to such ideas, may I suggest that a successful strategy involves humouring the idea whilst backing up your thoughts with good science. Consider this; is it likely that you will change the mind of the poster who has presented anti-scientific ideas? Or is it more likely that the general audience, some of whom maybe uncertain on such matters presented, be enlightened by your responses and seek to learn more? If you feel that you cannot address such posts without resort to personal attack / provocation then, quite frankly, you need to carefully consider whether you should post here. Play nicely now. Cheers Campermon

[halucigenia]

OK, back into the fray.
Contrary to what some other posters may seem to think, I think that questioner121 might possibly be able to be taught something. I even think that he might have picked up a little understanding of evolutionary theory as this thread has progressed as per some of his comments below.

I don't think you quite understand. I'm talking about how migration initially started.

I think that I do understand what you are trying to convey. However, as far as we know ever since organisms existed there may have been some form of migration, for example the daily migration of plankton in the seas from the depths to the surface could have been happening since the very first organisms in the seas existed, so that would be the ultimate initial start of migration. So the ability to migrate may have been built in to all organisms from the very start.
You probably mean how migration initially started in any one species that was not known to migrate before a certain point in time though, so let’s go with that shall we?

Using NS you'd have to select for a number of traits to get to migration.

I agree, several traits make up the ability to migrate. The organism requires to be mobile for a start, it needs to be able to navigate too. However both these traits are useful for actions other than strict migration, so they could have been selected for these other uses, couldn’t they?

These traits would all have to be accumulative.

The process of evolution results in the accumulation of traits over time. So when you consider that the individual traits that have to accumulate for an organism to have the ability to migrate, then as each of these traits could be useful for things other than migration, they can be selected for by natural selection prior to the initiation of migration in any one species, couldn’t they?
Or maybe you actually mean conglomerative (all at once) rather than accumulative (step by step over time)? If that is the case, then you’d be wrong as the traits used for migration are not exclusively used for migration alone, are they?

The longer your time span for migration to evolve the more chances there are for changes in the environment and animal to take place.

Yes, this is true for the evolution of any trait or group of traits – a truism. But what you probably mean is that the conditions may change to something different from what the migration would be useful for, don’t you? Which is just putting the cart before the horse by expecting there to be a prior direction for the evolution of the migration to aim for. As you should know by now – this is not how evolution works. The act of migration has to be performed before it can be “seen” by natural selection to be a successful strategy i.e. the organisms that do migrate have to successfully replicate those genes which contribute to their ability to migrate for those genes to be increased in the gene pool. Now, you may object to this on the grounds that you would not expect that long distance migration for example would be possible to be successful as a first step for this process to work. However, that is not what is proposed by those who understand how migration could have evolved. It could have been a gradual process - as you stated “The longer your time span for migration to evolve the more chances there are for changes in the environment” – changes in the environment that, for instance, force the organism to travel further over the generations.

NS does not mean the most able animal will survive. Whichever animal survives and reproduces is the animal which will pass on it's genes.

Able is a relative term – as it may be the least able to fly but the most able to swim that is the best able to replicate it’s genes by migrating to breeding colonies (thinking of penguins here).
Or how about puffins? Have you ever seen them flying – they’re not very “able” being better adapted to being efficient swimmers rather than fliers, however, they do migrate from their feeding grounds to their breeding grounds every year. I was in Iceland last year and witnessed puffins for the first time myself, its comical that they spend so much effort getting off the water and into the air that they leave long trails across the water and when they finally get into the air they furiously flap their tiny wings to keep themselves aloft seemingly barely able to keep above the waves. How they manage to migrate at all with this “ability” is amazing. Little is known about their migration habits, but maybe they swim most of the way? Though in decline for many years they seem to be “able” to fly, swim and migrate sufficiently successfully to be able to be successful in replicating their genes without being the best “able” to fly.
How did they start to migrate with this limited ability to fly I hear you ask. Simply the best able to follow their food and the ones that used the best place to have their breeding colonies were the most successful in replicating the genes that provided them with the abilities to have this successful migratory lifestyle and being in different areas the best strategy was to move between them. On the other hand it may have just happened that these different areas – the best food areas and the best breeding areas – changed over time to be in different locations due to changing environmental conditions.
You may still object that we don’t actually “know” “step by step” how this happened but what I am trying to show is that the above scenarios are at least plausible as your objections are mainly of the type that you can’t personally conceive how this happened. You, yourself don’t actually have evidence that it could not possibly have happened this way now, do you?

I'm sorry but it looks like what I am trying to say isn't making sense to anyone here.

I am trying to make sense of what you are saying in an attempt to help you understand.

I'm not challenging how some birds may get selected for if they migrate or don't migrate.

But that is how migration evolves, by organisms that are successful in replicating their genes being selected by natural selection because they do, or do not, migrate. What makes them migrate in the first place may not be directly attributable to evolution or natural selection selecting “for” migration, it may just be one of many possible behaviours that have evolved independently for other uses i.e. wide ranging foraging being successful in finding food being selected as a successful strategy and specific breeding sites being selected as places where the organism is more successful in being able to replicate their genes.

It's fairly obvious that those birds which are in a favourable environment will survive and go on to reproduce.

Yes, and this is how the process of evolution works. So, the process of evolution is actually obvious to you then?

What I'm challenging is that the actual process of migration (the behaviour and physiological features) didn't come about through NS.

Really, I don’t think so as your objections below regard traits that do not necessarily have to be selected just for migration to be possible as they are also used for more general survival strategies.

Birds did not develop the navigation system they use by NS.

Maybe not for the sole purpose of migration, but navigation systems are useful and can be selected for example for the use of finding feeding areas and finding breeding areas.

Birds did not learn where to migrate using NS.

But they may have been successfully selected to feed in the most productive areas and selected to breed in the most successful areas.

Birds did not develop the ability to fly long didstances by NS.

Again, maybe not for the sole purpose of migration, however the ability to fly long distances to find food or find breeding areas that enabled the organism to more successfully replicate its genes could have been selected for.

All these things are inherent in them and there is absolutely no evidence to say they developed these traits by NS. There is only speculation as to how these traits were developed.

Speculations based on observations that organisms that are better able to find food and use better breeding areas are more successful in reproducing than ones that don’t are all that is needed to infer that evolution by selection for these traits is certainly a plausible mechanism. What’s your plausible mechanism?

Apparently it is impossible through natural means for a mobile animal capable of traveling large distances to have developed behaviours favourable to it's own reproductive success.

And how do you think it developed it?

By observing it's surroundings and making decisions which made life easier.

If it was by 'observing it's surroundings and making decisions which made life easier' how does that fit in with NS?

Do you understand how it got them traits? Random chance or by deciding to have them?

That’s a false dilemma. It could have been random mutations being selected by non random natural selection selecting traits that enabled the organism to be better in replicating it’s genes by giving it the ability to be better at observing it's surroundings and making decisions which made life easier.

Well it's done fine for the past few millions of years. Can't be that badly designed. If it was down to evolution I'd be expecting it to be swinging from the bamboo shoots by now.

And what exactly would give you this expectation?

I think I'm beginning to understand where the evolutionists on this forum are coming from. They assume that variations in animals is natural so it's perfectly possible to have a mutations which give birds a navigation system, for zebras to have stripes, for peacocks to have extravagant feathers, etc. The only thing I'm unclear is on are these mutations big bang or did they develop gradually over millions of years? Did bird migration start of with a basic navigation system, did the zebras start of having grey stripes which deepened to black, did the peacock start off having 1 feather which then became 100+?

So it is clear to you that that natural variations arising from mutations can provide organisms with the traits that we observe them to have that serve them better to replicate their genes. And you still have a problem with understanding evolution because you are unclear whether these mutations are postulated to be big bang (macro-mutations) or relatively small mutations?
Would it help to suggest that macro-mutations providing “hopeful monster” type evolution are very much less likely to be beneficial than small mutations that can accumulate over time?
Or are you just leading back to the “they can’t be small over a long time as migration patterns can change rapidly” non sequitor? As I think that this has already been sufficiently addressed above.

I think gene mutations are 'natural' but for a gene mutation to actually develop a well functioning trait is something that is unusual to say the least. If you look at the genetic level, a mutation to create, let's say for example, an extra digit on a persons hand doesn't just mean creating an extra finger but also wiring it up to the brain, plugging it into the blood circulation system, maintaining it, etc.

As has already been explained “wiring it up to the brain, plugging it into the blood circulation system, maintaining it” are previously evolved developmental processes that do not have to re-evolve for any relatively minor physiological change. So that is not a valid objection.

I can understand it if evolutionists think it's perfectly naturally for animals in a population to have an extra digit here or there, different coloured skins, different shaped beaks, etc. But I don't think evolutionists understand that it's not a simple matter of a genetic mutation at the molecular level. It needs to encompass a significant proportion of the animals DNA in order to make the genetic mutation viable.

All it takes is for minor genetic mutations at the molecular level to be supported by already evolved developmental processes to occur and accumulate over time. You don’t need to propose “hopeful monster” macro-mutations for evolution to be able to proceed.

Richard Dawkins uses that analogy of a Boeing 747 macro-mutation compared to a stretched DC8 mutation in The Blind Watchmaker to explain this and it’s well worth reading to understand why you are wrong about this.
Richard Dawkins: The blind Watchmaker:CHAPTER 9 PUNCTURING PUNCTUATIONISM

I’ll stop the post here – it’s already too long. I might keep a more regular look into this thread if time permits and Q gives any reasonable responses to this post. Otherwise see you in another couple of weeks time.

[Shrunk]

Re: campermon's mod note:

I would argue there is also value in subjecting creationists to the open, unrestrained ridicule that their ideas deserve. It probably won't change their minds, but it might encourage then to keep those ideas to themselves. This would be similar to the use of quarantine to contain the spread of biological pathogens. Creationism is an intellectual pathogen.

[Spearthrower]

Re: campermon's mod note:

I would argue there is also value in subjecting creationists to the open, unrestrained ridicule that their ideas deserve. It probably won't change their minds, but it might encourage then to keep those ideas to themselves. This would be similar to the use of quarantine to contain the spread of biological pathogens. Creationism is an intellectual pathogen.

It's just possible that there might be some people left who would be surprised that I agree wholeheartedly; probably people who haven't been reading this thread.

[DarthHelmet86]

Re: campermon's mod note:

I would argue there is also value in subjecting creationists to the open, unrestrained ridicule that their ideas deserve. It probably won't change their minds, but it might encourage then to keep those ideas to themselves. This would be similar to the use of quarantine to contain the spread of biological pathogens. Creationism is an intellectual pathogen.

It's just possible that there might be some people left who would be surprised that I agree wholeheartedly; probably people who haven't been reading this thread.

Never! You are such a nice and upstanding man with no use of sarcasm at all...ever. And never any naughty words or angry posts, to say you did would be... blasphemy.

[Spearthrower]

Re: campermon's mod note:

I would argue there is also value in subjecting creationists to the open, unrestrained ridicule that their ideas deserve. It probably won't change their minds, but it might encourage then to keep those ideas to themselves. This would be similar to the use of quarantine to contain the spread of biological pathogens. Creationism is an intellectual pathogen.

It's just possible that there might be some people left who would be surprised that I agree wholeheartedly; probably people who haven't been reading this thread.

Never! You are such a nice and upstanding man with no use of sarcasm at all...ever. And never any naughty words or angry posts, to say you did would be... blasphemy.

And you know what we do with blasphemers round here, dontcha?

[campermon]

Re: campermon's mod note:

I would argue there is also value in subjecting creationists to the open, unrestrained ridicule that their ideas deserve. It probably won't change their minds, but it might encourage then to keep those ideas to themselves. This would be similar to the use of quarantine to contain the spread of biological pathogens. Creationism is an intellectual pathogen.

Ridicule the ideas, yes.

But this is discussing the modnote and thus very naughty!

Perhaps you could start a new thread on this?

[CharlieM]

Plus, polydactyly is observed fairly frequently in various cat breeds. Here's a news item featuring a polydactyl cat. Cats normally have five toes on the front paws, and four on the rear. This cat has 7 on the front, and 6 on the rear. All of them fully operational. Indeed, in the past, polydactyl cats were regarded as not only being omens of good luck amongst sailors in the days of sailing ships, but were valued for their enhanced climbing ability and rodent hunting skills.

None of this is a problem for those of us who bothered to study actual biology.

If extra digits bring such benefits why has the pentadactyl limb been such an enduring feature over the course of vertebrate evolution since land animals emerged? this makes sense from the point of view archetypal forms.

[Rumraket]

Plus, polydactyly is observed fairly frequently in various cat breeds. Here's a news item featuring a polydactyl cat. Cats normally have five toes on the front paws, and four on the rear. This cat has 7 on the front, and 6 on the rear. All of them fully operational. Indeed, in the past, polydactyl cats were regarded as not only being omens of good luck amongst sailors in the days of sailing ships, but were valued for their enhanced climbing ability and rodent hunting skills.

None of this is a problem for those of us who bothered to study actual biology.

If extra digits bring such benefits why has the pentadactyl limb been such an enduring feature over the course of vertebrate evolution since land animals emerged? this makes sense from the point of view archetypal forms.

Who says it "brings such benefits" ? It doesn't even have to be particularly beneficial for it to achieve fixation in a small population. That can happen simply through drift alone. What is more often the case with respect to natural selection is simply that it isn't sufficiently deleteriouos or outright lethal to carriers.

You've got the whole thing backwards. The pentadactyl limb has been conserved exactly because it is beneficial, and the reason we don't see any large-scale divergence in digit numbers is because it isn't particularly beneficial. But that doesn't mean it is impossible for the feature to evolve and achieve fixation in a population. The only question is if and for how long it will persist.

[theropod]

Turtle toes, count 'em.

Bird toes, count 'em.

Lizard toes, count 'em.

Cow toes, count 'em.


RS

[Fenrir]

Eight Little Piggies

An essay by Stephen Jay Gould

[Spearthrower]

Plus, polydactyly is observed fairly frequently in various cat breeds. Here's a news item featuring a polydactyl cat. Cats normally have five toes on the front paws, and four on the rear. This cat has 7 on the front, and 6 on the rear. All of them fully operational. Indeed, in the past, polydactyl cats were regarded as not only being omens of good luck amongst sailors in the days of sailing ships, but were valued for their enhanced climbing ability and rodent hunting skills.

None of this is a problem for those of us who bothered to study actual biology.

If extra digits bring such benefits why has the pentadactyl limb been such an enduring feature over the course of vertebrate evolution since land animals emerged? this makes sense from the point of view archetypal forms.

What benefits are you saying it claims they bring?

Also, please look up the idea of metabolic cost.