CharlieM wrote:Animavore wrote:CharlieM wrote:Shrunk wrote:Your point seems to be that if someone accuses Intelligent Design of being nothing more than creationism which has been renamed to hide this fact, you can refute that person's claim by providing examples where ID proponents deny that ID is creationism.
No I'm responding to Rumraket's post linking to creationist sites. He thinks that by doing this he is somehow arguing against intelligent design. I was pointing out that the sites he linked to criticise and distance themselves from ID. Its no secret that there are creationists in the ID movement, but there are also people with world views which are opposite to creationism. The search for design is a scientific enterprise no matter what the person's motives for searching.
Who are these people honestly searching for design? Where are their research teams? What is their field?
I've not come across one person with a screed of integrity from the ID crowd. Not one person with the gumption to ask honest questions on how to look for design or what to expect in biologically designed systems. No one even considering the serious implications of actually discovering evidence for design.
All I've come across at best is a bad case of apophenia and at worst outright lies and fruadulence.
What about Doug Axe and the team at the
Biologic Institute?
You mean the two people employed to be liars for doctrine, by deliberately NOT properly testing evolutionary postulates, and never actually searching for design at all? Their entire research output has been nothing but attempts to falsify "neo-Darwinism" by deliberately constructing strawmen of the process of evolution, then declaring something along the lines that evolution is not up to the job when their deceptive strawman is knocked down.
Case in point, let's take a loot at the work of Discovery institute bioengineers Douglax Axe and Ann Gauger, who in their ironic attempt to disprove evolution, end up disproving design and confirming evolution (as we shall see when we take a hard look at what they actually did, and how the research SHOULD have been done).
This is a "paper" from Doug Axe and Ann Gauger of the BioLogic-institute:
http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2011.1The Evolutionary Accessibility of New Enzymes Functions: A Case Study from the Biotin PathwayAnn K. Gauger, Douglas D. Axe
Abstract
Enzymes group naturally into families according to similarity of sequence, structure, and underlying mechanism. Enzymes belonging to the same family are considered to be homologs--the products of evolutionary divergence, whereby the first family member provided a starting point for conversions to new but related functions. In fact, despite their similarities, these families can include remarkable functional diversity. Here we focus not on minor functional variations within families, but rather on innovations--transitions to genuinely new catalytic functions. Prior experimental attempts to reproduce such transitions have typically found that many mutational changes are needed to achieve even weak functional conversion, which raises the question of their evolutionary feasibility. To further investigate this, we examined the members of a large enzyme superfamily, the PLP-dependent transferases, to find a pair with distinct reaction chemistries and high structural similarity. We then set out to convert one of these enzymes, 2-amino-3-ketobutyrate CoA ligase (Kbl2), to perform the metabolic function of the other, 8-amino-7-oxononanoate synthase (BioF2). After identifying and testing 29 amino acid changes, we found three groups of active-site positions and one single position where Kbl2 side chains are incompatible with BioF2 function. Converting these side chains in Kbl2 makes the residues in the active-site cavity identical to those of BioF2, but nonetheless fails to produce detectable BioF2-like function in vivo. We infer from the mutants examined that successful functional conversion would in this case require seven or more nucleotide substitutions. But evolutionary innovations requiring that many changes would be extraordinarily rare, becoming probable only on timescales much longer than the age of life on earth. Considering that Kbl2 and BioF2 are judged to be close homologs by the usual similarity measures, this result and others like it challenge the conventional practice of inferring from similarity alone that transitions to new functions occurred by Darwinian evolution.
The great irony here is that Axe and Gauger inadvertently test one of the popular (and very ad-hoc) design-postulates, but deliberately ignore the evolutionary postulate.
They
don't do ancestral sequence reconstruction and try to infer the
most probable ancestral sequence using phylogenetic maximum likelyhood trees (as evolutionary biologists would have them do). Instead, they do what many design-proponents postulate their designer did, they take one sequence (Kbl2)
and try to directly convert it into another distantly related structural homologue (BioF2), mutation by mutation.
They discover that doing this BREAKS THE FUCKING ENZYME. It stops working.
Seemingly affirming the many claims of the creationists and ID proponents, that mutations invariably destroy function, that there are too large distances of nonfunctionality between isolated "islands" of function in the conceptual phenotypical space of protein functions.
But this is
not what evolution postulates took place, this is NOT what is done with ancestral sequence reconstruction. Here both sequences (actually more, you need 3 orthologues sequences or more to do ancestral sequence reconstruction) evolved from a different common acestor to both of them, they did not change directly one
into the other. There was a long history of divergence from a common ancestor, that took a totally different evolutionary route than the direct conversion Axe and Gauger is attempting, and the result of which they deceptively use to insinuate falsifies evolution. This is DELIBERATE INCOMPETENCE, they're PAID to be liars.
I made a nice little drawing for you:
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These people simply cannot be trusted to accurately report or even test the facts of the matter. It's all part of an elaborate ruse to produce religious converts. Stop deluding yourself.
There are hundreds of excellent publications
by actual competent evolutionary biologists and biochemists, utilizing
ancestral sequence reconstruction to test ancient versions of extant proteins, and they all CURIOUSLY find functional intermediates, contrary to Axe and Gauger's deceptive pretensions.
A good recent paper on this that I've linked before here is this:
http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001446Reconstruction of Ancestral Metabolic Enzymes Reveals Molecular Mechanisms Underlying Evolutionary Innovation through Gene DuplicationKarin Voordeckers equal contributor, Chris A. Brown equal contributor, Kevin Vanneste, Elisa van der Zande, Arnout Voet, Steven Maere mail, Kevin J. VerstrepenAbstract
Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine.
This is how actually testing the true evolutionary postulate looks. You infer the most probably ancestral sequence to a set of extant homologues, and then you express and test it's functionality. You don't just convert one extant enzyme directly into another, like Axe and Gauger did.
Author Summary
Darwin's theory of evolution is one of gradual change, yet evolution sometimes takes remarkable leaps. Such evolutionary innovations are often linked to gene duplication through one of three basic scenarios: an extra copy can increase protein levels, different ancestral subfunctions can be split over the copies and evolve distinct regulation, or one of the duplicates can develop a novel function. Although there are numerous examples for all these trajectories, the underlying molecular mechanisms remain obscure, mostly because the preduplication genes and proteins no longer exist. Here, we study a family of fungal metabolic enzymes that hydrolyze disaccharides, and that all originated from the same ancestral gene through repeated duplications. By resurrecting the ancient genes and proteins using high-confidence predictions from many fungal genome sequences available, we show that the very first preduplication enzyme was promiscuous, preferring maltose-like substrates but also showing trace activity towards isomaltose-like sugars. After duplication, specific mutations near the active site of one copy optimized the minor activity at the expense of the major ancestral activity, while the other copy further specialized in maltose and lost the minor activity. Together, our results reveal how the three basic trajectories for gene duplicates cannot be separated easily, but instead intertwine into a complex evolutionary path that leads to innovation.
A great figure that shows this:
Figure 2. Duplication events and changes in specificity and activity in evolution of S. cerevisiae MalS enzymes.
The hydrolytic activity of all seven present-day alleles of Mal and Ima enzymes as well as key ancestral (anc) versions of these enzymes was measured for different α-glucosides. The width of the colored bands corresponds to kcat/Km of the enzyme for a specific substrate. Specific values can be found in Table S2. Note that in the case of present-day Ima5, we were not able to obtain active purified protein. Here, the width of the colored (open) bands represents relative enzyme activity in crude extracts derived from a yeast strain overexpressing IMA5 compared to an ima5 deletion mutant. While these values are a proxy for the relative activity of Ima5 towards each substrate, they can therefore not be directly compared to the other parts of the figure. For ancMalS and ancMal-Ima, activity is shown for the variant with the highest confidence (279G for ancMalS and 279A for ancMal-Ima). Activity for all variants can be found in Table S2.
doi:10.1371/journal.pbio.1001446.g002
As you can see, the original ancestral enzyme has low substrate specificity and is functionally promiscous(it catalyzes reactions from all the different substrates(colors), but at a low reaction rate(the thickness of the bars). Subsequently it gets duplicated, and daughter enzymes acquire novel mutations that change the substrate specificity, vastly increasing the reaction-rates for a smaller subset of substrates, sometimes losing functionality entirely for specific substrates.
We have other good threads on ASR and interesting functional applications on this very forum:
http://www.rationalskepticism.org/evolution/new-paper-lends-additional-support-to-a-thermophilic-luca-t39943.html?hilit=ancestral%20sequence%20reconstruction If you bother to actually read the first paper I introduce in that thread, you will see the biologists in question go out of their way to actually test their theories, elaborating on many common pitfalls and shaky assumptions.
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