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.)
Ok, so to be clear, you are now admitting that some parts of the genome are more susceptible to mutation than other parts right Allan?
Are we getting something definitive from you?
phoodoo,
You are yanking my chain, right?
Dazz queried whether the mutation rate was constant along the genome, and in my reply to that I agreed that it wasn’t. But I had not said that it was, only that mutation has no information as to where the sensitive genes are.
The causes of mutation variance are not due to a given region being ‘special-gene’ or ‘not-special-gene’.
Right, so what we are trying to get at, is WHAT IS the cause of some regions being less susceptible to mutations.
But let’s make sure we stay on point Allan, you acknowledge not all parts of the genome experience mutations rate the same, Ok?
If one were a suspicious type, one might think you are wavering on committing to a position, but Ok, now we got that down.
Are you taking at jab at me there? Why don’t you try to understand what’s being said here instead of digging yourself into a deeper hole?
Why would you think that?
But it’s clever if the guys actually engage in it. A Darwin Award goes to John Avise:
http://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780195393439.001.0001/acprof-9780195393439-chapter-4
phoodoo,
Are you trolling me?
At no point have I claimed anything other than these two, perfectly compatible, positions.
1) Hox genes are subject to the same mutational load as the rest of the genome.
2) The rate of mutation along the genome is not precisely constant.
Now, you can make LOTS of capital out of that, because, well, dog will hunt. I can hear you now: “if there is variation along the genome, how can any part of the genome be subject to the same load, because it’s all different!!!!”
Well, my position on both points has not changed, and been amply clarified already. HOX genes are not exceptional in their susceptibility to mutation. AFAIK, at least.
Consier the primate Alus. As pointed out by Avise and Ayala new Alu copy-and-paste insertions lead to disabilities. This suggest, the effect of novel Alus where they should not be is bad juju.
So then how did the primate genome tolerate such an explosion of Alu copying, and in the case of humans 1 million copies. Do you think we can willy nilly insert 1 million new Alu copies without killing a human?
It seems the Alus which come in nicely paired mirror images delimiting apparently well defined stretches of DNA that either form chromatin extrusion loops and/or dsRNA circles in the transcriptome have to be where they are, lest bad things happen. Hence the Alu elments are common design features of primates.
It’s a pretty good explanation, imho, why primates didn’t die from a random explosion of hundreds of thousands of Alu copies supposedly parasitizing the genome. It’s a lot better explanation than random Alu copying that just magically avoided wiping out the primates (the genetic load would be intolerable under selection) and then end up being a centerpiece for development of the primate central nervous system. Oh, that’s the other thing, Alu’s are part of a primate-specific regulatory and developmental strategy for the Central Nervous System (CNS) relative to other mammals or creatures with brains, don’t they? How’d that happen except by common design.
stcordova,
Sure, if the genome is mostly junk!
stcordova,
Dunno, to be honest. But correlation is not causation.
Common descent?
Given everything you’ve said, and given how different common design and common descent are in their mechanisms can you think of a single thing that if observed (or, indeed not) would demonstrate which one is true?
If you can’t does that not give you pause?
Then why isn’t it common throughout mammals?
Or do apes and humans have a common designer that is not common to other mammals?
Rhetorical question, I know, since you don’t think about these things beyond saying “God did it,” along with whatever superficial reason satisfies your incurious apologetics.
Glen Davison
stcordova,
Sal has apparently already forgotten what claim he was asked to support, but he knows it was something about Alu insertions and junk DNA, so quotes from a document containing some of those words.
The primate genome tolerated such an explosion because most of it is junk, so most Alu insertions do nothing, neither beneficial nor deleterious. Of course the million copies weren’t all inserted at once, as you seem to imagine, but over a long period, in different individuals. The strongly deleterious ones were eliminated quickly from the population. This is ordinary population genetics. Do you understand nothing about biology other than that you can find complicated diagrams to post?
The picture below is Buggs and Nelson’s apparent re-working of a data from this paper:
https://www.researchgate.net/publication/51606747_Evolutionary_Origin_of_Orphan_Genes
I think their re-working is materially accurate after looking at the source document.
What this shows is how Taxonomically Restricted Genes (Orphans) defy common descent progression. One would suppose the bars might be about the same size, certainly not pop out at the genus level as one traverses the taxonomic hierarchy from
Eukaryote -> Opishtokanta ….. -> Drosphilla Genus …->Melanogaster ….
This is indicative that gradual common descent with slight modification is not a great explanation as it suggest something more punctuated, like a poof.
No, Glenn, the common design of apes and humans would be more similar than that of humans to other mammals- just follow Linnaean taxonomy
Allan Miller,
Common Descent doesn’t account for the arrival of nerves in the first place. What would the first nerve do without all of the ions and pumps in place? And even given that it would need something to innervate or it would be useless.
Talk about evidence for a common design and the nervous systems fits in nicely
John Harshman,
Do you think evolutionary theory is now dependent on a high level of the genome being junk?
Are you claiming that the genus Drosophila is a created kind? I suspect you will be unwilling to commit on any such claim. But if not, your argument makes no sense whatsoever even on its own terms. How many of these orphan genes do you know have no homolog in other insects?
And once again you ignore the vast preponderance of data — all that data showing common descent among Diptera, Endopterygota, Insecta, etc. — in favor of a minor potential mystery.
Spelling flames: It’s Opisthokonta, Drosophila is always in italics and so is melanogaster, and the latter is never capitalized and never properly mentioned alone, without at least a D. in front.
No. Are you trying to turn into Mung?
What’s curious about Alus is that you can treat them as mini-genomes and construct phylogenies, independent of phylogenies of the organisms in which they reside. There are numerous different families of them and, curioser still, they map onto organismal phylogenies. You can see where one family arose, pick up where it acquired a mutation or three, where transposition rates pick up or decline, and so on.
And because a particular insert is a binary signal, they are very useful for resolving those very organismal phylogenies. While the gross class of Alus may be argued to have myriad functions, they can’t all fulfil all those functions at once, and some must equally be supposed to be nonfunctional, unless there is no such thing. The mode of motion around the genome – something you can observe in ‘real time’, near as dammit, among close relatives – renders Common Design rather poor as an explanation for a particular insert copy’s presence in a group of genomes.
John, evolution is supposed to be a theory of CHANGE. Why do you point to similarities to make a case for it? And given recombination why would we expect genetic markers to exist after thousands or millions of generations of change?
stcordova,
It’s that signal-noise thing again, Sal. Even if orphan genes did pop up fully formed in a lineage, what does the rest of the genome argue for?
Sure, some mobile element insertions (MEIs) cause problems, which is one reason why we tend to see fewer MEIs in exons than expected by chance. However, given the relatively high rate of new germline insertions (estimates are somewhere around 1 new germline insertion for every 20 births) and the huge extent of polymorphisms found when sequencings even a modest number of genomes, it is quite clear that a majority of MEIs are probably not very harmful. For example, one recent study (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002236#s2) sequenced ~180 individuals and found more than 7,000 MEI polymorphisms (~ 5,000 not present in the reference genome and ~2,000 present in the reference but not in some of the genomes they sequenced). Pretty much every study that looks that this finds lots of variability when it comes to MEIs.
stcordova,
The original version of this from Tautz & Domazet-Lošo has a time component (see below). By taking the time component out and retaining the taxonomic information, it is not at all clear to me what the new version of the figure is supposed to demonstrate.
Dave Carlson,
Let’s remember that Sal doesn’t believe in millions of years, and thus in “founder genes emergence per million years”, nor, I suppose, does he believe in any real taxonomic hierarchy beyond the created kind, which he will not identify. And thus that figure must be doubly meaningless to him, at the least.
Frankie,
The patterns of both similarities and differences are informative.
I’ll give you a serious answer, though I know what you’re like …
When such a sequence is rare, it will tend to either be excised or retained as a piece in heterozygotes. That’s just down to the mechanics of crossover, which requires homologous (matching) sequence. You’ll get LLLLLLRRRRRR on one chromosome at synapsis, and LLLLLLTRANSPOSONRRRRRR on the other, and even if the complementary LLLLLL and RRRRRR sequences align, you won’t get a crossover in the middle of that duplex, but – if anywhere – in LLLLLL or RRRRRR, which match. You can certainly lose transposons that way, but you gain an equal number on average. What doesn’t tend to happen is much internal slicing, because the transposon sequence is unmatched in heterozygotes.
OTOH if a transposon becomes common, internal recombinational crossovers will become more common in homozygotes, because now you do get matching sequence but – because they are homozygous – these won’t make any difference.
You don’t get a bunch of chopped-up transposons floating about, in short.
Dave Carlson,
Let us note that the genome sampling isn’t all that great. According to Wikipedia (https://en.wikipedia.org/wiki/List_of_sequenced_animal_genomes#Insects), most sequenced dipteran genomes are Drosophila species, most of the rest are mosquitos of various genera. And the remaining 3 are transcriptomes only. Now, as more genomes are sequenced, the number of total orphan genes is bound to go up. But the number of Drosophila melanogaster orphan genes is bound to go down.
True, indeed. I’m currently working on revisions to a manuscript where I attempted to quantify orphan genes in several species using transcriptomes. There are lots of them, however I’m working (or was when I did this research) in a taxonomic group that has extremely poor genomic sampling. I’m pretty sure that sampling bias in existing sequence databases accounts for a considerable portion of the observed orphans in my taxa.
Problems with gene model predictions from newly sequenced genomes is an important issue as well. There is a reason why the number of protein coding genes predicted to be present in the human genome has dropped significantly since the draft genome was first published.
But you don’t know what can account for the anatomical and physiological differences.
And thank you for your response. I think we are talking past each other and that is my fault for not being more specific and coherent. Let me see if I can better convey my meaning at a later date.
And of course transcriptomes will not identify non-coding sequences homologous to the orphan genes.
Dave,
Thank you for you inputs. Do you determine the genes by looking solely at the transcriptome or do you use gene prediction? If you determine genes by the transcriptome, how many cell types do you survey?
I’m presuming, as of yet we really don’t confirm existence of proteins in the proteome by proteomic sequencing. It’s too expensive. We really don’t know the proportion of post translational proteins are further protein spliced.
I was focusing specifically on coding sequences, so I used gene prediction methods designed to pull those from transcripts. It was it an exploratory and certainly not exhaustive effort.
Correct, AFAIK. Bioinformatic prediction of protein sequences from nucleotides is vastly more common than proteomics, especially for nonmodel organisms.
I might point out Larry Moran might really [snark] love [/snark] this development:
http://europepmc.org/abstract/MED/21296742
Non-protein coding RNA (ncRNA) genes? Yay!
For humans I heard one figure of 20,000 RNA genes. That number sounds inflated. I have to check on that. But do we count ncRNAs as orphans as well? What about those dsRNAs that Alus make? How about circular RNAs? Do we have names for these critters yet and are we willing to call these things genes too?
John Harshman,
Yep.
You seem to be missing an important distinction. If scientific research ends up supporting some position Moran previously rejected, he changes his position to match the science. Contrast to creationists who simply DENY the science and never learn a damn thing.
I see nothing in your quoted paragraph that Moran would have difficulty with.
stcordova,
Ah, the Gish Gallop. Gotta love it. I’ll leave it to someone else to point out to Sal that Larry knows all about ncRNA genes and they don’t affect his claims about junk DNA.
For the last year I’ve been trying to find a paper I can’t seem to get a hold of anymore on the Phantom Transcriptome. Was it redacted or what? It relates a claim that 10% of the human genome has transcripts that seem to have no analogue in the genome. I’ve tried unsuccessfully to find the paper.
On a related note, it is worth mentioning a lot of RNAs escape our notice which may be important to function because they simply disappear before we can sequence them.
https://en.wikipedia.org/wiki/Cryptic_unstable_transcript
These too can qualify as ncRNA “orphans” if they are indeed orphan RNAs.
Sal always does that. He ignores the positive arguments for jDNA and just keeps repeating the same mantra that it’s all an argument from ignorance.
Not news to you or everyone else who’s used to deal with him, of course.
I wonder if some of the pros can shed some light on this. 3,000 ncRNA genes were found, but what did it take in terms of explored sequence length to identify them?
stcordova,
Why is the Discovery Institute not funding lab time to find functionality in jDNA instead of publishing books about fucking origami cranes?
Good question. I’m sure someone there might be willing to answer your questions if you send them a donation. 🙂
But to a more serious question about ncRNA genes, the most famous is related to your obsession with Hox genes. Hox genes control other genes by the famous ncRNA gene called HOTAIR (acronym for HOX Transcript Anti-sense RNA).
I pointed HOTAIR out to Larry when he was going on his usual tirade and was lambasting lncRNAs in particular. I told Larry we can’t write off lncRNAs yet because we have examples (like HOTAIR) of them regulating protein coding genes, and many more of them (maybe tens of thousands) could be discovered.
The HOTAIR lncRNA goes from chromosome 12 to Chromsome 2 and 832 other locations (on different chromosomes) to regulate gene expression. It represses gene activity by connecting to a molecular machine called the PRC2 (polycomb repression complex 2).
This PRC2 machine then parks on the target gene, and modifies a single amino acid residue on a specific histone (histone 3) and adds a teeny-weeny methylation mark on the histone that suppresses the target gene. Freaking amazing. Depicted below is a the product of an ncRNA gene (HOTAIR) in action. This picture also shows the LSD1 complex demethylating other histone amino acids (something I just learned myself).
But there is more than just HOTAIR, the Hugo list which you find so alarming is open to the public for perusal:
http://www.genenames.org/cgi-bin/genefamilies/set/788
John Rinn thinks 41,000 more HOTAIR-like ncRNA genes exist.
Thank you very much for your response, I was actually wondering how professionals identify genes.
stcordova,
Not a professional in the sense of getting paid just yet. 🙂
dazz,
Seriously, compare Larry’s tirade against lncRNAs
http://sandwalk.blogspot.com/2016/09/how-many-lncrnas-are-functional-can.html
to the blog (URL below) that actually covers lncRNAs. The stuff is technical, but it’s easy to see, people who actually research lncRNAs have good reason to suppose many of them are functional. You are getting a distorted view from Larry. I’m merely trying to broaden your horizons.
I urge the same for VJ Torley before he embraces too much of what Larry says. Larry’s views may have been half-way viable 10 years ago, but they are becoming increasingly marginal in today’s environment.
See this blog on lncRNAs and compare with the way Larry charactersizes lncRNAs
.
http://www.lncrnablog.com/category/news/headlines/
Eureka! I found the citation for 20,000 ncRNA genes. And where else was this found except in that institution that Dan Graur loathes, the National Institutes of Health.
Well, this is premature in many respects, but let’s wait and see.
stcordova,
Hi Sal
What is the typical length of LncRNA’s?
I don’t think there is a typical length except to say it must be a minimum of 200 bases (a totally arbitrary number) to qualify. I’ve seen averages in the ball park of 1000, but please please don’t stand by that number. I think the range of numbers is pretty wide:
when average sizes were published, it was usually for specific classes and species. For example in this species of bees the number was 790bp.
By comparison, the famous HOTAIR gene is 12,649 bases!
Btw, HOTAIR genes can create alternatively spliced HOTAIR transcripts. Many lncRNAs are alternatively spliced, btw!
So the lncRNA gene is probably a lot BIGGER than the RNA transcript it generates in general because the lncRNA may emerge from genes with introns, but don’t quote me on that yet.
There are fewer that 1000 proven genes for noncoding RNAs in the human genome. These include ribosomal RNAs (~300), tRNAs (~120), and all the other well-characterized RNAs such as snRNAs, miRNAS, and snoRNAs. In addition there is a large category of possible genes for RNAs like lncRNAs etc.
Dozens of labs have been working hard for several decades to find out how many of these are biologically functional. The latest count is about 400 and that’s based on knock-out experiments and sequence conservation.
When I’m describing genomes, I usually assume there are, or will be, about 5,000 noncoding RNA genes when the dust settles. This seems like a reasonable number.
There can’t be huge numbers of such genes because we have good evidence that 90% of the genome is junk. That doesn’t leave much room for undiscovered noncoding genes.
stcordova says,
“… people who actually research lncRNAs have good reason to suppose many of them are functional.”
This is a surprise? Of course they want as many as possible to be functional otherwise they won’t be able to publish. Unfortunately, they haven’t had much success in proving to anyone else that a significant fraction are actually functional.
It’s getting a bit embarrassing.
Well, thanks for your response, and you do have a point about publication.
FWIW, you and Mike Behe and Allan Miller inspired some interest in me to learn more about biochemistry.
So whatever things I’ve said critical of your views, it’s nothing personal, and I have the highest respect for people in the disciplines of chemistry.
cheers