De-Novo Gene Origination from protogenes.

Incl. intelligent design, belief in divine creation

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De-Novo Gene Origination from protogenes.

#1  Postby GenesForLife » May 16, 2014 2:14 pm

Good paper.

http://www.nature.com/nature/journal/v4 ... 11184.html

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo1, 2. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described1, 2. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or ‘non-genic’ sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions1, 3, 4, 5, 6. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes4 generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential7, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.


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Re: De-Novo Gene Origination from protogenes.

#2  Postby Calilasseia » May 16, 2014 8:05 pm

Full paper available from here. :)
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Re: De-Novo Gene Origination from protogenes.

#3  Postby Animavore » May 16, 2014 8:06 pm

Why's this in 'creationism'.
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Re: De-Novo Gene Origination from protogenes.

#4  Postby Calilasseia » May 16, 2014 8:38 pm

Additional paper to add to the collection:

Phylogenetic Patterns Of Emergence Of New Genes Support A Model Of Frequent De Novo Evolution by Rafik Neme & Diethard Tautz, BMC Genomics, 14: 117 -128 (21st February 2013) [Full paper downloadable from here]

Neme & Tautz, 2013 wrote:Abstract

Background: New gene emergence is so far assumed to be mostly driven by duplication and divergence of existing genes. The possibility that entirely new genes could emerge out of the non-coding genomic background was long thought to be almost negligible. With the increasing availability of fully sequenced genomes across broad scales of phylogeny, it has become possible to systematically study the origin of new genes over time and thus revisit this question.

Results: We have used phylostratigraphy to assess trends of gene evolution across successive phylogenetic phases, using mostly the well-annotated mouse genome as a reference. We find several significant general trends and confirm them for three other vertebrate genomes (humans, zebrafish and stickleback). Younger genes are shorter, both with respect to gene length, as well as to open reading frame length. They contain also fewer exons and have fewer recognizable domains. Average exon length, on the other hand, does not change much over time. Only the most recently evolved genes have longer exons and they are often associated with active promotor regions, i.e. are part of bidirectional promotors. We have also revisited the possibility that de novo evolution of genes could occur even within existing genes, by making use of an alternative reading frame (overprinting). We find several cases among the annotated Ensembl ORFs, where the new reading frame has emerged at a higher phylostratigraphic level than the original one. We discuss some of these overprinted genes, which include also the Hoxa9 gene where an alternative reading frame covering the homeobox has emerged within the lineage leading to rodents and primates (Euarchontoglires).

Conclusions: We suggest that the overall trends of gene emergence are more compatible with a de novo evolution model for orphan genes than a general duplication-divergence model. Hence de novo evolution of genes appears to have occurred continuously throughout evolutionary time and should therefore be considered as a general mechanism for the emergence of new gene functions.
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Re: De-Novo Gene Origination from protogenes.

#5  Postby Calilasseia » May 16, 2014 8:42 pm

Animavore wrote:Why's this in 'creationism'.


Probably because over in E&NS, the scientifically literate, whilst regarding the papers as interesting additions to the literature, wouldn't regard the science as controversial, whilst the usual suspects here in creationism will almost certainly try to erect the usual canards, which these papers destroy quite neatly. :)

Having said that, I'll generate a shadow topic in E&NS for this thread, so that the science can be accessible therefrom, whilst any creationist propaganda is kept in its proper place. :mrgreen:
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Re: De-Novo Gene Origination from protogenes.

#6  Postby Calilasseia » May 16, 2014 8:52 pm

Another paper for the collection:

Origins Of New Genes And Evolution Of Their Novel Functions by Yun Ding, Qi Zhou and Wen Wang, Annual Review of Ecology, Evolution, and Systematics 43: 345-363 (December 2012) [Full paper downloadable from here]

Ding et al, 2012 wrote:Abstract

The origination of novel genes is an important process during the evolution of organisms because it provides critical sources for evolutionary innovation. Addressing how novel genes emerged and acquired novel and adaptive functions is of fundamental importance. Here we summarize the newest advances in our understanding of the molecular mechanisms and genome-wide patterns of new gene origination and new gene functions. We pay special attention to the origins of noncoding RNA genes and de novo genes, whose processes had been previously overlooked but are gaining increasingly visible importance. We then introduce recent findings that have opened a path to the study of the evolution of novel functions and pathways via novel genes. We also discuss the important issues and potential developments in the field.
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Re: De-Novo Gene Origination from protogenes.

#7  Postby Rumraket » May 16, 2014 8:57 pm

:coffee:
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Re: De-Novo Gene Origination from protogenes.

#8  Postby GenesForLife » May 16, 2014 9:43 pm

Animavore wrote:Why's this in 'creationism'.


Because it is likely to be more read by people here, firstly, and secondly it debunks creationist canards regarding gain of information and associated bollocks quite nicely.
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Re: De-Novo Gene Origination from protogenes.

#9  Postby Rumraket » May 17, 2014 7:09 am

GenesForLife wrote:
Animavore wrote:Why's this in 'creationism'.


Because it is likely to be more read by people here, firstly, and secondly it debunks creationist canards regarding gain of information and associated bollocks quite nicely.

Yes I've raised a similar point on Larry Moran's blog before. There's a colossal contradiction between the creationists resistance to junk-DNA and their simultaneous insistance that mutations invariably always degrades information and biopolymers into nonfunctionality.

The junk-DNA is evolving at a neutral rate (which is just one piece of evidence among several, that it reall is junk). That means there is no purifying selection weeding out "bad" mutations. The implication should be obvious. If creationists really think the junk regions aren't actually junk, but are all functional, then they will have to concede there is no amount of mutation that can render the genome nonfunctional.

The funny thing, not only are the creationists wrong about both their resistance to junk DNA and their claims that mutations always degrade information. In addition to the massive contradiction between these two claims, the reality actually turns out to be diametrically opposite to their assertions. Mutations in the junk regions routinely creates new functional genes simply through chance (yes, this time truly and actually just chance)*. Inevitably the accumulation of mutations will create promoter and enhancer regions in random places in the junk, resulting in transcripts with sequences that have been evolving neutrally for a long time, meaning the sequences will be random. Some of these will even go on to be translated. Whether they remain as RNA or become fully fledged protein coding genes, if they turn out to have some kind of function selection can hone and improve on the result.

*I can already see creationist heads exploding.
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Re: De-Novo Gene Origination from protogenes.

#10  Postby Rumraket » May 17, 2014 1:32 pm

Relatedly:
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004351
The Case for Junk DNA
Alexander F. Palazzo , T. Ryan Gregory

Overview

With the advent of deep sequencing technologies and the ability to analyze whole genome sequences and transcriptomes, there has been a growing interest in exploring putative functions of the very large fraction of the genome that is commonly referred to as “junk DNA.” Whereas this is an issue of considerable importance in genome biology, there is an unfortunate tendency for researchers and science writers to proclaim the demise of junk DNA on a regular basis without properly addressing some of the fundamental issues that first led to the rise of the concept. In this review, we provide an overview of the major arguments that have been presented in support of the notion that a large portion of most eukaryotic genomes lacks an organism-level function. Some of these are based on observations or basic genetic principles that are decades old, whereas others stem from new knowledge regarding molecular processes such as transcription and gene regulation.


The junk-DNA concept IS NOT AN ARGUMENT FROM IGNORANCE.
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Re: De-Novo Gene Origination from protogenes.

#11  Postby DavidMcC » May 18, 2014 2:04 pm

Rumraket wrote:Relatedly:
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004351
The Case for Junk DNA
Alexander F. Palazzo , T. Ryan Gregory

Overview

With the advent of deep sequencing technologies and the ability to analyze whole genome sequences and transcriptomes, there has been a growing interest in exploring putative functions of the very large fraction of the genome that is commonly referred to as “junk DNA.” Whereas this is an issue of considerable importance in genome biology, there is an unfortunate tendency for researchers and science writers to proclaim the demise of junk DNA on a regular basis without properly addressing some of the fundamental issues that first led to the rise of the concept. In this review, we provide an overview of the major arguments that have been presented in support of the notion that a large portion of most eukaryotic genomes lacks an organism-level function. Some of these are based on observations or basic genetic principles that are decades old, whereas others stem from new knowledge regarding molecular processes such as transcription and gene regulation.


The junk-DNA concept IS NOT AN ARGUMENT FROM IGNORANCE.

Indeed, not!
AFAIK, the main category of "junk DNA" refers to sequences that make up the chromatin "packaging" that wraps round the actual genes most of the time. This has the important function of helping to prevent "accidental" gene expression. Genes can only be expressed after the chromatin around them has "fluffed up". This should be seen as funtional DNA, even though it is not active in terms of translating into any RNA, because it could easily be fatal to a multicellular organism if any particular cell expresses any inappropriate genes at a significant level. Thus, "junk DNA" is a misnomer in any case, and should have been abandoned long ago, perhaps in favour of something like "permanently silent DNA", or whatever.
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Re: De-Novo Gene Origination from protogenes.

#12  Postby DavidMcC » May 18, 2014 2:38 pm

... Perhaps "passive DNA" would be a better term to substitute for "junk DNA". It's also snappier!
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Re: De-Novo Gene Origination from protogenes.

#13  Postby GenesForLife » May 18, 2014 5:08 pm

AFAIK, the main category of "junk DNA" refers to sequences that make up the chromatin "packaging" that wraps round the actual genes most of the time.


Nope -

[1] DNA alone never makes up chromatin packaging.
[2] Chromatin consists of histones in combination with DNA.
[3] Heterochromatin (which is highly compacted and wraps around silent DNA) does not wrap around genes.
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Re: De-Novo Gene Origination from protogenes.

#14  Postby DavidMcC » May 18, 2014 5:52 pm

GenesForLife wrote:
AFAIK, the main category of "junk DNA" refers to sequences that make up the chromatin "packaging" that wraps round the actual genes most of the time.


Nope -

[1] DNA alone never makes up chromatin packaging.
[2] Chromatin consists of histones in combination with DNA.
...

Ha! A classic case of interpretation issues. The fact that the chromatin includes DNA is sufficient to make my arguent valid.
[3] Heterochromatin (which is highly compacted and wraps around silent DNA) does not wrap around genes.

Fair enough, but it doesn't invalidate my argument that much "junk DNA" has a function - one of suppressing accidental gene expression.
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Re: De-Novo Gene Origination from protogenes.

#15  Postby GenesForLife » May 18, 2014 6:39 pm

DavidMcC wrote:
GenesForLife wrote:
AFAIK, the main category of "junk DNA" refers to sequences that make up the chromatin "packaging" that wraps round the actual genes most of the time.


Nope -

[1] DNA alone never makes up chromatin packaging.
[2] Chromatin consists of histones in combination with DNA.
...

Ha! A classic case of interpretation issues. The fact that the chromatin includes DNA is sufficient to make my arguent valid.



Piffle. You don't get chromatin that contains junk DNA wrapping around genic DNA to regulate it. PPS - chromatin doesn't wrap round DNA either, DNA is wrapped around histones and the entirety, which is called chromatin, is either compacted or not.


[3] Heterochromatin (which is highly compacted and wraps around silent DNA) does not wrap around genes.

Fair enough, but it doesn't invalidate my argument that much "junk DNA" has a function - one of suppressing accidental gene expression.


Junk DNA does not suppress accidental gene expression - histone marks in genic chromatin are sufficient to model gene expression and does not need the invocation of heterochromatin being wrapped round gene as a determinant. Activatory and repressive histone marks DO NOT depend on junk DNA to be established. I should have been more precise - heterochromatin doesn't wrap around silent DNA, heterochromatin is made of silent DNA in combination with histones carrying exclusively repressive histone marks.

Reference for predictive modelling of gene expression from histone mark profiles http://genomebiology.com/2012/13/9/r53
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Re: De-Novo Gene Origination from protogenes.

#16  Postby Rumraket » May 18, 2014 8:31 pm

DavidMcC wrote:
Rumraket wrote:Relatedly:
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004351
The Case for Junk DNA
Alexander F. Palazzo , T. Ryan Gregory

Overview

With the advent of deep sequencing technologies and the ability to analyze whole genome sequences and transcriptomes, there has been a growing interest in exploring putative functions of the very large fraction of the genome that is commonly referred to as “junk DNA.” Whereas this is an issue of considerable importance in genome biology, there is an unfortunate tendency for researchers and science writers to proclaim the demise of junk DNA on a regular basis without properly addressing some of the fundamental issues that first led to the rise of the concept. In this review, we provide an overview of the major arguments that have been presented in support of the notion that a large portion of most eukaryotic genomes lacks an organism-level function. Some of these are based on observations or basic genetic principles that are decades old, whereas others stem from new knowledge regarding molecular processes such as transcription and gene regulation.


The junk-DNA concept IS NOT AN ARGUMENT FROM IGNORANCE.

Indeed, not!
AFAIK, the main category of "junk DNA" refers to sequences that make up the chromatin "packaging" that wraps round the actual genes most of the time.

No, the main category of junk is deactivated transposable elements. Retro transposons. Mostly this is mutated reverse transcriptase genes that have selfishly inserted themselves all over the genome many many times. At a rate that is higher than random deletion events could have got rid of it. That's the largest fraction of the junk, but not the only junk.

DavidMcC wrote:This has the important function of helping to prevent "accidental" gene expression.

No, it might inadvertently have that effect. But that effect is evidentially not strong enough to confer a selective advantage to the extend that we can reliably expect promotion of such "protective junk" or whatever you might want to call it. Evidence for absense of this postulated selective contraint is found in the huge variations of genome size even within very closely related species. Case in point - The Onion test.

Another line of evidence that seems to contradict your postulate here is the almost total absense of such "protective junk" from most single-celled organisms.

DavidMcC wrote: Genes can only be expressed after the chromatin around them has "fluffed up".

Well, you mean genes can only be expressed into RNA transcripts when the double helix has been unwound and helicase has "unzipped" the double strand. Pervasive transcription (also sometimes called transcriptional noise or noisy transcription) at low levels is an observed fact.
Otherwise functional transcription factors will simply occasionally randomly attach to neutrally evolving sequence and produce a transcript (as shown both through in vitro experiments with transcription factors binding to random stretches of DNA, and through measured expression levels in vivo).
Exactly because the reckognition-site is most often not totally identical to the "intended" target site, the binding affinity is lower and the expression level will consequently be extremely low.

DavidMcC wrote:This should be seen as funtional DNA, even though it is not active in terms of translating into any RNA

You mean transcribed, not translated. Also, it IS active in terms of being transcribed into RNA. That's basically the result of the whole ENCODE project. But again, as would be expected for simple biochemical reasons, neutrally evolving DNA will occasionally mutate into stretches of DNA with some sequence similarity to known enhancer and promoter regions. Consequently, we would simply expect occasional low-affinity binding of transcription factors to this randomly mutating DNA. This is what we observe, almost the entire genome is transcribed, but the vast majority is expressed at an extremely low level. When we say low level, we are talking expression levels below a single RNA transcript pr. cell. That is absurdly low. The implication here should be pretty obvious. That is very a very high probability just the result of a "noisy transcription".

DavidMcC wrote:because it could easily be fatal to a multicellular organism if any particular cell expresses any inappropriate genes at a significant level.

Yes, at a significant level. Which would require sequences with very high sequence similarity to known enhancer/promoter regions.

DavidMcC wrote:Thus, "junk DNA" is a misnomer in any case, and should have been abandoned long ago, perhaps in favour of something like "permanently silent DNA", or whatever.

David, maybe you should actually read the publication?

It's obvious there are many mechanisms at work that eventually result in the creation of unneeded and nonfunctional DNA sequence that doesn't have enough of a selective constraint operating on it to kill off carriers. A simple and famous example is the vitamin C pseudogene, GULOP. Do you really want to maintain the GULOP gene is being kept around to protect other genes? There are thousands of pseudogenes. Many of the retro transposons are a form of pseudogenes in themselves, being that they consist of deactivated reverse transcriptase genes that either initially originated in ancient viral infections, or emerged from mutated telomerase enzymes. Junk is simply a manifest fact.

We don't have to engage in this kind of ad-hoc, adaptationist rationalization. A lot of evolution is neutral and random, not everything has a selective purpose or advantage. We don't have to postulate that it does to explain it's existence or to understand it's origin and evolutionary history.
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Re: De-Novo Gene Origination from protogenes.

#17  Postby DavidMcC » May 19, 2014 12:49 pm

Look, I didn't invent this stuff - it was part of my "Basic Bio" course by my employer, which was active in the field of biotechnology (involving DNA amplification on electronic chips).
So, you two don't accept that portions of a chromosome untwist ("fluff up") during gene expression, to allow enzymes to access the gene? That was in my course, I didn't invent it. I was even shown a micrograph of a chromosome, showing fluffy portions, said to be the expressing regions. The theory was that multicellular animals exploit the extra protection of genes from enzymes, which are large molecules, except during expression.
I din't realise that it was all "piffle". Sorry.

Rumraket wrote:We don't have to engage in this kind of ad-hoc, adaptationist rationalization. A lot of evolution is neutral and random, not everything has a selective purpose or advantage. We don't have to postulate that it does to explain it's existence or to understand it's origin and evolutionary history.

That was not my argument. I was taught that a major difference between prokaryotes and eukaryotes involved the latter having to keep most genes in any one cell completely silent all of the time, otherwise the wrong proteins and RNAs might be made in that cell, which could be fatal. That was part of the rationale given.
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Re: De-Novo Gene Origination from protogenes.

#18  Postby DavidMcC » May 19, 2014 1:15 pm

Maybe you two have been misconstruing my wording.
http://en.wikipedia.org/wiki/Chromatin#Chromatin_and_bursts_of_transcription
Chromatin and bursts of transcription
Chromatin and its interaction with enzymes has been researched, and a conclusion being made is that it is relevant and an important factor in gene expression. Vincent G. Allfrey, a professor at Rockefeller University, stated that RNA synthesis is related to histone acetylation. The lysine amino acid attached to the end of the histones is positively charged. The acetylation of these tails would make the chromatin ends neutral, allowing for DNA access.
When the chromatin decondenses, the DNA is open to entry of molecular machinery. Fluctuations between open and closed chromatin may contribute to the discontinuity of transcription, or transcriptional bursting. Other factors are probably involved, such as the association and dissociation of transcription factor complexes with chromatin. The phenomenon, as opposed to simple probabilistic models of transcription, can account for the high variability in gene expression occurring between cells in isogenic populations[8]

The bolded bit is what I refered to as an important role of the chromatin DNA. Are you also denouncing this as "piffle"?
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Re: De-Novo Gene Origination from protogenes.

#19  Postby DavidMcC » May 19, 2014 3:45 pm

... I now have my old course notes (mainly printed by the lecturers) in front of me.
Section 4.1 Regulation at the structural level. Active genes: - unfolding of chromatin during transcription
Electron micrograph of active genes.
During transcription, the compact chromatin opens up and long loops of DNA being transcribed is visible.


(And, yes, I admit that I used the wrong word previously, OK? Obviously, I have not included the micrograph.)
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Re: De-Novo Gene Origination from protogenes.

#20  Postby DavidMcC » May 19, 2014 3:52 pm

... I also think you have the wrong idea about the evolutionary aspect of the above. It does not imply that "all junk DNA is chromatin, or that it evolved for a purpose", as you bizarrely inferred.
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