Early embryonic mutations: a problem for evolution?

Dr. Stephen Meyer and Dr. Douglas Axe were recently interviewed by author and radio host Frank Turek on the significance of November’s Royal Society Meeting on evolution, in London. The two Intelligent Design advocates discussed what they see as the top five problems for evolutionary theory:

(i) gaps in the fossil record (in particular, the Cambrian explosion);
(ii) the lack of a naturalistic explanation for the origin of biological information;
(iii) the necessity of early mutations during embryonic development (which are invariably either defective or lethal) in order to generate new animal body types;
(iv) the existence of non-DNA epigenetic information controlling development (which means that you can’t evolve new animal body plans simply by mutating DNA); and
(v) the universal design intuition that we all share: functional coherence makes accidental invention fantastically improbable and hence physically impossible.

In today’s post, I’d like to focus on the third argument, which I consider to be the best of the bunch. The others are far less compelling.

Over at the Sandwalk blog, Professor Larry Moran and his readers have done a pretty good job of rebutting most of these arguments, in their comments on Professor Moran’s recent post, The dynamic duo tell us about five problems with evolution (January 14, 2017). Larry Moran’s earlier 2015 post, Molecular evidence supports the evolution of the major animal phyla cites a paper by Mario dos Reis et al. in Current Biology (Volume 25, Issue 22, p2939–2950, 16 November 2015) titled, “Uncertainty in the Timing of Origin of Animals and the Limits of Precision in Molecular Timescales,” which convincingly rebuts Meyer and Axe’s first argument, by showing that animals probably originated in the Cryogenian period (720 to 635 million years ago) and diversified into various phyla during the Ediacaran period (635 to 542 million years ago), before the Cambrian. I might add that we now have strong evidence that anatomical and genetic evolution occurred five times faster during the early Cambrian, at least for arthropods – although as Intelligent Design advocates have pointed out, that still leaves unanswered the question of how animal body plans arose in the first place.

Meyer and Axe’s second argument asserts that natural processes are incapable (as far as we can tell) of creating significant quantities of biological information – and especially, new functions or new anatomical features. Much of the argument rests on the alleged rarity of functional proteins in amino acid sequence space – a claim that was crushingly refuted in Rumraket’s recent post on The Skeptical Zone titled, Axe, EN&W and protein sequence space (again, again, again) (October 12, 2016). As for the claim that natural processes can’t create new functions, it’s simply bogus. The following three papers should be sufficient to demonstrate its empirical falsity: Five classic examples of gene evolution by Michael Page (New Scientist Daily News, March 24, 2009), Evolution of colour vision in vertebrates by James K. Bowmaker (Eye (1998) 12, 541-547), and Adaptive evolution of complex innovations through stepwise metabolic niche expansion by Balazs Szappanos et al (Nature Communications 7, article number 11607 (2016), doi:10.1038/ncomms11607).

I’m not really qualified to discuss Meyer and Axe’s fourth argument, but it seems to me that Professor Larry Moran has addressed it more than adequately in his recent post, What the Heck is Epigenetics? (Sandwalk, January 7, 2017). The last four paragraphs are worth quoting (emphases mine):

The Dean and Maggert definition [of epigenetics] focuses attention on modification of DNA (e.g. methylation) and modification of histones (chromatin) that are passed from one cell to two daughter cells. That’s where the action is in terms of the debate over the importance of epigenetics.

Methylation is trivial. Following semi-conservative DNA replication the new DNA strand will be hemi-methylated because the old strand will still have a methyl group but the newly synthesized strand will not. Hemi-methylated sites are the substrates for methylases so the site will be rapidly converted to a fully methylated site. This phenomenon was fully characterized almost 40 years ago [Restriction, Modification, and Epigenetics]. There’s no mystery about the inheritance of DNA modifications and no threat to evolutionary theory.

Histone modifications are never inherited through sperm because the chromatin is restructured during spermatogenesis. Modifications that are present in the oocyte can be passed down to the egg cell because some of the histones remain bound to DNA and pass from cell to cell during mitosis/meiosis. The only difference between this and inheritance of lac repressors is that the histones remain bound to the DNA at specific sites while the repressor molecules are released during DNA replication and re-bind to the lac operator in the daughter cells [Repression of the lac Operon].

Some people think this overthrows modern evolutionary theory.

So much for epigenetics, then.

The fifth and final argument discussed by Drs. Meyer and Axe relates to the universal design intuition. I’ve already amply covered both the merits and the mathematical and scientific flaws in Dr. Axe’s book, Undeniable, in my comprehensive review, so I won’t repeat myself here.

The “early embryo” argument, helpfully summarized by Dr. Paul Nelson

That leaves us with the third argument. Looking through the comments on Professor Moran’s latest post, it seems that very few readers bothered to address this argument. The only notable exception was lutesuite, who pointed out that examples of non-lethal mutation in regulatory DNA sequences are discussed in a paper titled, Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change by M.Z. Ludwig et al. (Development 1998 125: 949-958). The paper looks interesting, but it’s clearly written for a specialist audience, and I don’t feel qualified to comment on it.

As it turns out, I wrote about the “early embryo” argument in a 2012 post, when it was being put forward by Dr. Paul Nelson. Nelson handily summarized the argument in a comment he made over at Professor Jerry Coyne’s Website, Why Evolution Is True:

Mutations that disrupt body plan formation are inevitably deleterious. (There’s only one class of exceptions; see below.) This is the main signal emerging from over 100 years of mutagenesis in Drosophila.

Text from one of my Saddleback slides:

1. Animal body plans are built in each generation by a stepwise process, from the fertilized egg to the many cells of the adult. The earliest stages in this process determine what follows.

2. Thus, to change — that is, to evolve — any body plan, mutations expressed early in development must occur, be viable, and be stably transmitted to offspring.

3. But such early-acting mutations of global effect are those least likely to be tolerated by the embryo.

Losses of structures are the only exception to this otherwise universal generalization about animal development and evolution. Many species will tolerate phenotypic losses if their local (environmental) circumstances are favorable. Hence island or cave fauna often lose (for instance) wings or eyes.

Obviously, loss of function is incapable of explaining the origin of new, viable body plans for animals.

A hole in the argument?

On the face of it, Nelson’s three-step argument certainly looks like a knock-down argument, assuming that the premises are factually true. But are they? A commenter named Born Right made the following response to Dr. Nelson over at Jerry Coyne’s Website (emphases mine):

Paul Nelson,

Lethal mutations will kill the embryo. But what you’re totally failing to understand is that not all mutations are lethal. Many are tolerated. I heard you cite the example of HOX gene mutations in flies and how altering them kills the embryos. You didn’t mention the entire story there. Do you know that there are wild populations of flies having HOX gene mutations? Even in the lab, you can create viable HOX-mutant flies that have, for example, two sets of wings. In fact, simple non-lethal mutations in HOX genes can profoundly alter the morphology. It is these non-lethal mutations that natural selection “cherry picks”, provided they confer a survival advantage on the organism.

Many mutations actually arise as recessive mutations, not as dominant ones. They spread through the population remaining dormant or having a mild effect, until there is a sufficient number of heterozygotes. Then, interbreeding between heterozygotes will cause homozygous mutations to arise suddenly throughout the population. If the new feature improves survival & reproductive success, it gets rapidly selected…

Macroevolution is a gradual response to climate change and other environmental pressures. Organisms accumulate non-lethal mutations that changes their body plan bit by bit until they are well adapted to their changing habitat.

However, a 2010 Evolution News and Views post co-authored by Dr. Paul Nelson, Dr. Stephen Meyer, Dr. Rick Sternberg and Dr. Jonathan Wells, contests the claim that Hox gene mutations are non-lethal. The authors assert that such mutations are, at the very least, defective:

Mutations to “genetic switches” involved in body plan formation … disrupt the normal development of animals. With the possible exception of the loss of structures (not a promising avenue for novelty-building evolution, in any case), these mutations either destroy the embryo in which they occur or render it gravely unfit as an adult. What the mutations do not provide are “many different variations in body plans.”…

… [T]here are solid empirical grounds for arguing that changes in DNA alone cannot produce new organs or body plans. A technique called “saturation mutagenesis”1,2 has been used to produce every possible developmental mutation in fruit flies (Drosophila melanogaster),3,4,5 roundworms (Caenorhabditis elegans),6,7 and zebrafish (Danio rerio),8,9,10 and the same technique is now being applied to mice (Mus musculus).11,12

None of the evidence from these and numerous other studies of developmental mutations supports the neo-Darwinian dogma that DNA mutations can lead to new organs or body plans–because none of the observed developmental mutations benefit the organism.

Indeed, the evidence justifies only one conclusion, which Wells summarized in his last slide at SMU:

“We can modify the DNA of a fruit fly embryo in any way we want, and there are only three possible outcomes:
A normal fruit fly;
A defective fruit fly; or
A dead fruit fly.”

The Wikipedia article on Drosophila embryogenesis may interest some readers.

What I would like to know is: are the Hox mutations in fruitflies mentioned by Born Right in his comment above neutral or deleterious – and if the latter, are they only slightly deleterious or highly deleterious?

A follow-up comment by Born Right

In a subsequent comment over at Why Evolution Is True, Born Right cited two scientific references in support of his claims:

Paul Nelson,

Fantastic new research shows how fish developed limbs and moved onto land. Boosting the expression of Hoxd13a gene in zebrafish transforms their fins into limb-like structures that develop more cartilage tissue and less fin tissue!

http://www.sciencedaily.com/releases/2012/12/121210124521.htm

http://www.sciencedirect.com/science/article/pii/S1534580712004789

Importantly, the overexpression of Hoxd13a in zebrafish was driven by a mouse-specific enhancer. This shows that the regulatory elements acting on the enhancer are present in both fishes and distantly-related mammals!

The first paper, titled, From fish to human: Research reveals how fins became legs (Science Daily, December 10, 2012) is written in a style that laypeople can readily understand. I’ll quote a brief excerpt (emphases mine):

In order to understand how fins may have evolved into limbs, researchers led by Dr. Gómez-Skarmeta and his colleague Dr. Fernando Casares at the same institute introduced extra Hoxd13, a gene known to play a role in distinguishing body parts, at the tip of a zebrafish embryo’s fin. Surprisingly, this led to the generation of new cartilage tissue and the reduction of fin tissue — changes that strikingly recapitulate key aspects of land-animal limb development. The researchers wondered whether novel Hoxd13 control elements may have increased Hoxd13 gene expression in the past to cause similar effects during limb evolution. They turned to a DNA control element that is known to regulate the activation of Hoxd13 in mouse embryonic limbs and that is absent in fish.

“We found that in the zebrafish, the mouse Hoxd13 control element was capable of driving gene expression in the distal fin rudiment. This result indicates that molecular machinery capable of activating this control element was also present in the last common ancestor of finned and legged animals and is proven by its remnants in zebrafish,” says Dr. Casares.

This sounds fascinating, and to me it constitutes powerful evidence for common ancestry, but the real question we need to address is; exactly how early in the course of the zebrafish’s embryonic development did these mutations take effect?

The second paper cited by Born Right (“Hoxd13 Contribution to the Evolution of Vertebrate Appendages” by Renata Freitas et al. in Developmental Cell, Volume 23, Issue 6, pp. 1219–1229, 11 December 2012) is much meatier, because it’s the original papaer on which the Science Daily report was based. The authors contend that “modulation of 5′ Hoxd transcription, through the addition of novel enhancer elements to its regulatory machinery, was a key evolutionary mechanism for the distal elaboration of vertebrate appendages,” and they conclude:

Within the developmental constraints imposed by a highly derived teleost fin, our results suggest that modulation of Hoxd13 results in downstream developmental changes expected to have happened during fin evolution. This, together with the evidence we provide that the upstream regulators of CsC were also present prior to tetrapod radiation, makes us favor an evolutionary scenario in which gain of extra 5′ Hoxd enhancers might have allowed the developmental changes necessary for the elaboration of distal bones in fishes that evolved, ultimately, into the tetrapod hand.

This sounds a lot more promising, but after having a look at it, I’m still rather unclear about exactly how early these hypothesized mutations would have had to have occurred, in the course of vertebrate embryonic development. Perhaps some reader can enlighten me.

Well, that’s about as far as my digging and delving has taken me. I’d like to throw the discussion open at this point. Are there any known examples of early embryonic mutations which are not deleterious, and do they shed any light on how new animal body plans might have evolved? Over to you.

(Note: the image at the top [courtesy of Wikipedia] shows the ventral view of repeating denticle bands on the cuticle of a 22-hour-old Drosophila embryo. The head is on the left.)

585 thoughts on “Early embryonic mutations: a problem for evolution?

  1. Acartia:
    I apologize if this has already been discussed, but I am far too lazy to read through all 200+ comments.

    But Axe and Meyer lost all credibility when they included number v in their list:

    Only a moron would think that that is an actual argument.

    That’s OK. Their target audience is morons.

  2. stcordova: By golly that was the best criticism I’ve gotten all day. Thank you.

    So I must fall back on Marcus Ross and Paul Nelson’s problem of the Uber Bilaterian instead.

    Probably should have read my whole post instead of just what dazz quoted. Then you would have seen my critique on Ross & Nelson’s ur-bilaterian. I’m assuming that “Uber” was just autocorrect and not ignorance.

  3. John Harshman: Do creationists never get tired of the crocoduck argument? The common ancestor of insects and vertebrates had no hard skeleton at all. At most it had a hydrostatic skeleton. There was no gradual transition from one to the other; there were a gradual transitions from no skeleton to a skeletion, twice, in separate lineages. We have fossils of some of those transitions, and there are living organisms that display some of the transitional stages. Stop reaching for zingers on subjects you know nothing about, unless you like embarrassing yourself.

    Thanks to the advent of the modern synthesis and all subsequent revisions, you have to unpack all of that by way of genetics. Until then it is just an interesting story- a working hypothesis.

  4. John Harshman: there were a gradual transitions from no skeleton to a skeletion, twice, in separate lineages.

    Gee, I wonder what that would look like, the first gradual application of a skeleton. What’s the first mutation? What evolutionary advantage might it have had?

    Good luck with that.

  5. stcordova,

    This is one example why I think common design optimized to help humans understand themselves is a better explanation than common descent with mindless modification.

    If that is its purpose, I think that’s a rather crap way of going about it. To have extensive sequence homology, be able to trace multiple duplication events, to align the entirety into a pattern that is entirely in accord with descent in exactly the same way that much more humble genes do within … uh .. baramins, when your intention is to show that it is something else entirely?

    ‘Common Design’ is my pick for the dumbest Creationist idea of them all.

  6. Mung,

    […] reprogramming[…]

    We’ve been down this road before. I say I don’t like to over-extend a particular metaphor, you give me loads of examples of people using the metaphor, I say I don’t care … [it’s more of an ‘initialise’ routine, anyway!]

  7. Mung,

    If this is something that was predicted by the theory, or entailed by the theory, then why was such sequence similarity just stunning?

    Evolutionary theory does not tell you what you’ll find when you look.

    Carroll’s intuition may have been that vastly different organisms had vastly different means of generating their endless forms. That, for that matter, would probably have been a “Designist’s” opinion too.

    That there proved to be an underlying digital unity is not exactly a disaster for evolutionary theory. People may trot out the old ‘oh yes, it’s Common Design, just as we’d expect’ argument. I would fix them with my best ‘oh, really?’ look.

  8. stcordova: The evolutionary reasoning goes something like this:

    Joe Evolutionist:

    a few copies, even 1 copy of Alu would suffice to provide whatever information it needs to, hence 1 million copies of Alus are obviously junk, not to mention Alus don’t code for anything.

    Can you give a reference to “Joe Evolutionist”, whoever that is, actually making this inference? Making up a crappy line of inference nobody actually engages in, and then laughing at it, isn’t that clever.

    I mean, if that’s really why someone thinks ALU elements are mostly junk, that “they don’t code for anything” and “one would be enough”, then sure that would be really stupid. I’ve just never come across anyone who thinks they’re mostly junk for those reasons.

    This Joe Evolutionist guy, he’s invisible right?

    That line of reasoning seemed unassailable probably for several decades

    Probably? How about you give a single reference to someone making that particular idiotic inference, and then another to someone else finding it persuasive a decade later.

  9. Mung: The enzymes are localized in the nucleus at this early stage of development, where the metabolites are needed for reprogramming the genome, rather than the mitochondria. Now that would be surprise enough — enzymes that every undergrad biology student learns are in the mitochondria are found in the nucleus early in development. That’s remarkable. And now they’re involved in embryonic genome activation.

    The mitochondrial genome encodes very few proteins. Most of it has been transferred to the nuclear genome, where most of the proteins are made, and then transferred from there to mitochondria. This isn’t some great big new surprise.

    There are some pretty strong selective reasons why this is so. For example, a single eukaryotic cell usually carries many mitochondria. Which means if the cell needs to divide, it will have to make many new mitochondria, so if the mitochondria had retained all their original genes, they’d have to be replicated many times (thus costing more energy and taking longer), rather than just replicated once when transferred to the nuclear genome.

    It does not seem that surprising to me that a product of the endosymbiosis that resulted in eukaryotes, in other words the very thing that makes and defines eukaryotes, is one of the things that eukaryotes also employ in the development of multicellular life.

  10. stcordova: Since it would appear the Alu structure is needed for enzymes and other molecular machines to bind to it in order for it to be edited and used as endpoints for dsRNAs, one can see the entire Alu is functional, thus 10-11% of the human genome that is made of Alus is likely functional.

    LOL. Somebody, somewhere, has found some functional ALUs. Therefore all the millions of them are functional. And only in humans of course. Or rather, they have special functions in humans (lemme guess, it’s in the brain right?) , and for other species they have other special functions. All of them. Just not as special in humans, with our special brain.

    How’s that for a conclusion that simply doesn’t follow. There shouldn’t be any “thus” between the statement and your conclusion. The fact that ALUs are edited by enzymes doesn’t make them functional. It is laughably ad-hoc and completely lacks any explanatory power for the inter-species patterns in the distribution of ALU elements. What a remarkable coincidence that the “common designer” commonly designed nesting hierarchical patterns in the inter-species distribution of ALU elements that mirrors standard primate phylogenies, for a piece of DNA known to be able to take advantage of cellular DNA editing and insertion mechanisms (wait.. what?) and proliferate itself.

    Nooo, all of that we can just safely ignore, or handwave away with “that’s what the designer wanted”. Why? Well he’s just that sort of guy I guess. I know him personally, he’s a bit of an artist.

  11. Rumraket,

    There are some pretty strong selective reasons why this is so. For example, a single eukaryotic cell usually carries many mitochondria. Which means if the cell needs to divide, it will have to make many new mitochondria, so if the mitochondria had retained all their original genes, they’d have to be replicated many times (thus costing more energy and taking longer), rather than just replicated once when transferred to the nuclear genome.

    I’d recommend Nick Lane’s Power, Sex, Suicide on mitochondria. It would look good on the shelf, anyway … 😉 The question of the transfer of genes to nucleus is addressed, but also the apparent puzzle as to why 13 remain (besides the RNAs).

    One of the drivers for transfer appears to be to stop mitochondria getting ideas above their station – the less autonomy, the less opportunity to start doing things in your own selfish interests like killing males or beating shit out of other mitochondria. Another is that mitochondrial genes experience free radical damage, due to their location next to unshielded plutonium (to speak metaphorically). Mitochondria have a significantly elevated mutation rate, and hence a reduced capacity to sustain a longer genome.

  12. Allan Miller:
    phoodoo,

    It’s termed ‘purifying selection’.

    No Allan, that is NOT a mechanism. You are so caught up in buying the whole evolution-speak, that you think some things remaining whilst some things die is a mechanism. I didn’t ask you why some genes remained, and some didn’t, I asked you what causes some genes to be susceptible to mutation, and some not to be?

    If we believe in evolution, then the CAUSE of some genes not being susceptible to mutation can ONLY be mutations caused them to not be susceptible to mutation!

    This is not only problematic for your side for the obvious reasons that how doe s a mutation cause something to not be susceptible to mutation, but it further would cause one to ask, then why doesn’t the entire genome of some species get mutations which leave them unable to get more mutations? Has this experiment been tried in nature and over ions turned out to be an unsuccessful reproduction plan? Because surely such mutations (which caused something to never get mutations) would work for some time, now wouldn’t it?

    If an organisms that already had a successful body plan, suddenly couldn’t get any mutations at all, good nor bad, it would have to survive for pretty long, since it was already in existence.

    But of course there is no such mutation which prevents mutations.

  13. phoodoo,

    You are so caught up in buying the whole evolution-speak, that you think some things remaining whilst some things die is a mechanism.

    You asked a short question, I gave a short answer. Why the diatribe?

    ‘Some things remaining while some things die’ is indeed a mechanism, although in the case of Hox genes it is more a matter that some things (the ones with mutations to the Hox genes) frequently don’t even develop.

    That is a perfectly sound explanation for conservation. It is exactly the same as the frequent Creationist complaints that ‘mutations are always lethal’, or ‘selection only eliminates’

    I’m not quite sure what rattled your cage on this occasion, but if you let me know, I’ll be sure to do more of it!

  14. phoodoo: If we believe in evolution, then the CAUSE of some genes not being susceptible to mutation can ONLY be mutations caused them to not be susceptible to mutation!

    Wut? It’s not that they’re not susceptible to mutation, it’s that those mutations are often deleterious enough to not propagate. IOW, they’re selected against = purifying selection. And yes, this is a mechanism with tons of explanatory power, and that should be obvious to anyone with half a brain cell.

    Embarrassing

  15. This is not only problematic for your side for the obvious reasons that how does a mutation cause something to not be susceptible to mutation, but it further would cause one to ask, then why doesn’t the entire genome of some species get mutations which leave them unable to get more mutations?

    There is no special protection afforded to Hox genes from mutation, nor does ‘purifying selection’ imply that there is, so I’m afraid I don’t follow this line of reasoning.

  16. Allan Miller: I’d recommend Nick Lane’s Power, Sex, Suicide on mitochondria. It would look good on the shelf, anyway … The question of the transfer of genes to nucleus is addressed, but also the apparent puzzle as to why 13 remain (besides the RNAs).

    I have (and have read) it, and the two later ones too: Life Ascending: The Ten Great Inventions of Evolution, and The Vital Question: Why is life the way it is?. There are so many curious facts about mitochondria and their hosts that evolution can make sense of.

  17. Allan Miller: There is no special protection afforded to Hox genes from mutation

    Then in what way can one say they are highly conserved?

    Do they experience the same rates of mutations as all other parts of the genome?

  18. Rumraket:

    The fact that ALUs are edited by enzymes doesn’t make them functional

    Ah, such dismissiveness and rush to judgement. When we do a full shut down A-to-I editing in mice it’s lethal. The mirror image pairs of Alus arrange themselves in the genome in amazing pairs like brackets around large DNA segments like this [ ….. ] in the genome, and then these bracketed DNA segments generate dsRNA transcripts that seem implicated in alternate splicing. Not to mention a few of the Alu-bracketed-DNAs are involved in controlling chromatin looping.

    You’re soooo sure Alus have no role. Why the rush to judgement and eagerness to support the 82.5 Megabytes Moran viewpoint? If you had the same eagerness for potential new frontiers of discovering how biology may work that you have for non-existent transitionals, you would be all over this discovery. But I sense some bias against these interesting possibilities.

    Let me quote some views on A-to-I editing from the mainstream. Contrast Larry “82.5 Megabytes” Moran’s characterization with the National Academy of Sciences on the topic of Alus:

    http://www.ncbi.nlm.nih.gov/pubmed/20566853

    These findings bring to mind information storage models. As the number of potential editing sites in each Alu-containing transcript is high, usually several dozens, the potential for combinatorial encrypted information is enormous. Binary use of A or I in millions of sites in the neural cell transcriptome can be considered equivalent to the 0’s and 1’s used for information storage and processing by computers. It is tempting to speculate that the more abundant RNA editing found in the human brain may contribute to the more advanced human capabilities such as memory, learning, and cognition. This suggestion is consistent with the hypothesis that the advantage of complex organisms lies in the development of a digital programming system based on noncoding RNA signaling (46, 56). The combinatorial posttranscriptional RNA editing of noncoding sequences may therefore contribute to higher brain functions and may play a role in the evolution of human specialization.

    Of this remarkable information potential, only a mere 7 years ago, world class evolutionary biologist Francisco Ayala makes himself the potential butt of jokes:

    Perhaps one could attribute the obnoxious presence of the Alu sequences to degenerative biological processes that are not the result of ID. But was the Designer incompetent or malevolent in not avoiding the eventuality of this degeneration?

    Francisco Ayala criticizing Stephen Meyer
    http://biologos.org/blogs/guest/on-reading-the-cells-signature

    But as I suggested to VJ Torely, the matter isn’t settled. Arm chair evolutionary nay-saying isn’t the way to settle the question of Alu functionality or wihether Larry “*82.5 Megabytes” Moran is right.

    You’re so quick to rush to judgement rather than show any eagerness to explore vast new frontiers of possibilities. Bill Nye the Science Guy would have some issues with that sort of nay saying as it’s a science stopping attitude.

    And

    From this paper:
    http://www.ncbi.nlm.nih.gov/pubmed/26803450

    Post-transcriptional RNA modification by adenosine to inosine (A-to-I) editing expands the functional output of many important neuronally expressed genes. The mechanism provides flexibility in the proteome by expanding the variety of isoforms, and is a requisite for neuronal function. Indeed, targets for editing include key mediators of synaptic transmission with an overall significant effect on neuronal signaling. In addition, editing influences splice-site choice and miRNA targeting capacity, and thereby regulates neuronal gene expression. Editing efficiency at most of these sites increases during neuronal differentiation and brain maturation in a spatiotemporal manner. This editing-induced dynamics in the transcriptome is essential for normal brain development, and we are only beginning to understand its role in neuronal function. In this review we discuss the impact of RNA editing in the brain, with special emphasis on the physiological consequences for neuronal development and plasticity.
    ….

    Initially only serendipitously identified single sites of editing were found by comparisons between the cDNA and the genomic sequence. However, the recent bloom of next-generation sequencing (NGS) has provided a powerful tool in detecting reliable levels of editing at numerous sites simultaneously. Currently, editing is predicted to occur at over a hundred million sites, with the vast majority positioned in primate-specific inverted repetitive elements of non-coding Alu sequences [13]. When transcribed as inverted repeats, Alus frequently form long stem-loop structures that are largely double-stranded…the number of possible editing sites in these elements is immense

  19. phoodoo: Then in what way can one say they are highly conserved?

    Do they experience the same rates of mutations as all other parts of the genome?

    You spend an inordinate amount of time bashing evolution but you don’t even understand the most basic concepts. Don’t you see a problem there?

  20. phoodoo,

    Then in what way can one say they are highly conserved?

    When one looks at different species, there is no, or very little, difference. The fewer the differences, the greater they are said to be ‘conserved’. The role of selection is an evolutionary viewpoint, but that’s what ‘evolutionarily conserved’ means.

    Do they experience the same rates of mutations as all other parts of the genome?

    Yes. The mutational ‘forces’ (polymerase errors, repair errors, DNA damage, disruptive recombinations) can’t really distinguish between genes at all. They act directly on the untranscribed DNA.

  21. Allan Miller: Yes. The mutational ‘forces’ (polymerase errors, repair errors, DNA damage, disruptive recombinations) can’t really distinguish between genes at all. They act directly on the untranscribed DNA.

    I thought there were known portions of the DNA with lower mutation rates

  22. dazz,

    I thought there were known portions of the DNA with lower mutation rates

    Yep, you’re right, but (AFAIK) this is not directly related to differential protection of some genes. It’s more mechanistic – recombinational hotspots, GC content bias, etc. Having said that, one of those papers indicates that transposons, at least, are underrepresented in Hox genes.

    But it would be hard to distinguish mutational protection from selection, in a region where most mutations were fatal. There are two possible sources of bias.

  23. Allan Miller: It’s more mechanistic – recombinational hotspots, GC content bias, etc.

    What is this trying to say Allan?

    I am not sure you know. GC content bias? etc??

  24. OK, after googling what GC content bias is, I seem to remember one discussion Larry Moran’s Sandwalk. It’s just a chemical propensity to produce more GC than AT

    And transposons being underrepresented in Hox genes… I read a few days ago that these genes are expressed sequentially, so moving one to a different location would break havoc in the development process

    Allan Miller: But it would be hard to distinguish mutational protection from selection, in a region where most mutations were fatal. There are two possible sources of bias.

    I think I get this. Since there’s so little variation it’s hard to tell if this is due to a lower mutation rate (mutational protection) or strong selective pressure to weed out variation. No idea what you mean by “sources of bias” though

  25. dazz,

    Are those mechanistic factors inheritable and subject to selection?

    Well … they are consistent. The ‘GC bias’ thing for example relates to the density of GC nucleotide pairs you have in a region. GC base pairs have 3 hydrogen bonds, AT have two, which has numerous consequences, plus A and T are just slightly ‘different’ from G and C in stacking and in their susceptibility to certain kinds of chemical attack or mismatch.

    In short: there are processes that tend to change the GC content of some areas (itself a mutation), which in turn changes their susceptibility to other mutational effects. GC content is heritable, but what I call ‘mechanistic’ effects are more to do with chemistry. Although, to confuse still further, that chemistry can influence selection.

  26. dazz,

    No idea what you mean by “sources of bias” though

    I mean that conservation only indicates a bias against change in a region, without saying definitively what that bias is due to. There are two main possible sources of that bias: reduced mutation and purifying selection.

  27. Allan Miller: There are two main possible sources of that bias: reduced mutation

    Reduced mutation is a possible source of bias against increased mutations???

  28. Allan Miller: Common Design’ is my pick for the dumbest Creationist idea of them all.

    When compared to Common Descent it is the least obtuse of the two concepts. And we actually have experience with Common Design.

  29. phoodoo,

    Allan Miller: There are two main possible sources of that bias: reduced mutation

    phoodoo: Reduced mutation is a possible source of bias against increased mutations???

    No. It is a possible source of bias against the null expectation: the neutral rate of evolution.

  30. Allan Miller:
    phoodoo,

    No. It is a possible source of bias against the null expectation: the neutral rate of evolution.

    You are continuing to conflate a mechanism for preserving genomics sequences, with a preference in reproduction for genes which are highly preserved.

    Are you suggesting there are mechanisms (completely unplanned and unguided mechanisms) which would cause some gene sequences to be more susceptible to mutations and some sequences less susceptible to mutation?

    And are you just giving some vague, see what sticks to the wall, description of that mechanism? Are you claiming that a preponderance of GC bonds rather than AT bonds is what has caused hox genes to be more conserved than other areas of the genome? Or is the mechanism somewhere in the “ETC” you threw out?

    Because I am contending that simply saying, well genes that are highly conserved are preferred by selection is not an explanation of any kind. Furthermore selection can only work on an individual organism. Either the organism survives or it doesn’t. So if every time that an organism died because it got a mutation to a hox gene, that would in no way create an organism which couldn’t get a mutation to its hox genes. What you would need is a mutation to a hox gene, which makes getting mutations to hox genes less likely. So in order to become less prone to mutation, you need to get the mutation which makes you less prone. And if you were less prone to mutation, you wouldn’t get the mutation that makes you less prone.

    So you need a situation where a genome is less prone to mutation EXCEPT for a mutation which makes you less prone; for that mutation you have to be MORE prone to getting a mutation!

    Which to anyone pondering the problem, would be cause for a rethink.

  31. vjtorley:
    Speaking of the human brain, I just came across a Live Science article saying that the human brain’s memory could store the entire Internet.

    I find the idea of billions of replicas of Uncommon Descent quite horrifying.

  32. Patrick: vjtorley:
    Speaking of the human brain, I just came across a Live Science article saying that the human brain’s memory could store the entire Internet.

    Bullshit.

  33. phoodoo: Because I am contending that simply saying, well genes that are highly conserved are preferred by selection is not an explanation of any kind

    Ironically Paul Nelson’s argument is predicated on the same principle you claim explains nothing.

  34. phoodoo,

    You are continuing to conflate a mechanism for preserving genomics sequences, with a preference in reproduction for genes which are highly preserved.

    No I’m not. If there were a bias against reproduction for mutated versions of a sequence, that would lead to ‘preservation’ of the sequence – a reduction in the apparent rate of change, as observed by taxonomic sampling.

    Are you suggesting there are mechanisms (completely unplanned and unguided mechanisms) which would cause some gene sequences to be more susceptible to mutations and some sequences less susceptible to mutation?

    No. I have already said that evolutionary conservation does not mean reduced mutation. You seem incapable of reading the term ‘conserved’ without imagining some kind of lead-lined casket heading the mutations off at source.

    But I think the basic problem here is your long-standing refusal to understand the term ‘selection’. Surely you can see that if individuals with mutations to certain genes always die as embryos, those genes would never change in the population, even if the genes themselves mutated at the same rate?

  35. Allan Miller:
    stcordova,

    If that is its purpose, I think that’s a rather crap way of going about it. To have extensive sequence homology, be able to trace multiple duplication events, to align the entirety into a pattern that is entirely in accord with descent in exactly the same way that much more humble genes do within … uh .. baramins, when your intention is to show that it is something else entirely?

    ‘Common Design’ is my pick for the dumbest Creationist idea of them all.

    I’m not sure. The various arguments that attempt to support the historicity of a global flood in the past few thousand years give Common Design a run for its money.

  36. Patrick,

    I’m not sure. The various arguments that attempt to support the historicity of a global flood in the past few thousand years give Common Design a run for its money.

    You have a point.

  37. Allan Miller: Surely you can see that if individuals with mutations to certain genes always die as embryos, those genes would never change in the population, even if the genes themselves mutated at the same rate?

    So are you claiming that hox genes( and all genes) have the same mutation rates as all other sequences in the genome? Its just that we would never see the result of mutated hox genes, because they would never come to fruition?

  38. phoodoo,

    So are you claiming that hox genes( and all genes) have the same mutation rates as all other sequences in the genome? Its just that we would never see the result of mutated hox genes, because they would never come to fruition?

    That’s pretty much it, yes.

    The stuff about GC content “etc” was a side-discussion with dazz, because he’d queried my statement, which did suggest the chance of mutation was exactly equal along the genome. It isn’t, but the mutation probability still does not correlate strongly with the kind of gene found at a given location.

  39. Allan Miller: It isn’t,

    The mutation rate along the genome is equal or isn’t equal Allan? You seem to be hinting at both positions. I think we need to at least settle on which you are saying.

  40. dazz: I thought there were known portions of the DNA with lower mutation rates

    You spend an inordinate amount of time supporting evolution but you don’t even understand the most basic concepts. Don’t you see a problem there?

    Embarrassing.

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