Do Endogenous Retroviral Sequences (ERVs) Prove Evolution? Yes, they do!

The following makes corrections (in red) to a blog page at "Evolution Dismantled". While scientists will point out that "proof" is not a concept in science, being constrained to mathematics, other axiomatic systems and to alcoholic beverages, ERVs do indeed prove in the legalistic sense of "establish beyond reasonable doubt", that common descent is true. Accused murderers have been found guilty or acquitted on much less substantial evidence.

The author ignores all the evidence that ERVs derive from retroviruses and attempts to argue from personal incredulity (a fallacy) that it is impossible for ERV components to furnish adaptive function, and that it is impossible for organisms to have acquired so many ERVs from retroviruses and survive.

Note: The author of the page repeatedly refuses to approve my comments on it. Here is the latest comment of mine that he keeps erasing, "Are you going to display any manners and respond to my offer of helping you with your re-write? And what errors did you find in my piece?" He/she would be most welcome to comment at the foot of this page, without fear of censorship. Readers are encouraged to post a link to this page in the discussion section of the original blog page. 

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Endogenous retrovirus.
Image credit: FreeDigitalPhotos.net by user ‘jscreationzs’ (Actually, this would be an exogenous retrovirus.)

Introduction

Don’t be put off by the big name. Endogenous means something that comes from within the organism or cell. This helps us understand that an EndogenousRetroViral sequence is a piece of DNA which was put in by a virus.

This is one of the few stronger evidences for the theory of evolution. Evolutionists think that a type of virus, called a ‘retrovirus’, once inserted DNA into our supposed ape ancestor. 

Actually, scientists have identified over 200,000 remains of insertions, from multiple retroviruses, over the history of the species concerned. 

Scientists have noticed that chimps and humans have these bits of viral DNA (“ERVs” for short) at very similar spots in our DNA. 

Not "similar spots". Precisely corresponding "spots" (loci), precise down to single DNA base-pair resolution.

So they say: our common ancestor acquired these ERVs and since humans and chimps are closely related, we should have them in similar spots in our genomes. We do. If we and chimps didn’t evolve from a common ancestor (which first acquired the ERVs), how is it possible that we and chimps have ERVs in almost precisely the same locations? The only plausible explanation, evolutionists say, is evolution.

However, if we can show that ERVs were not put in by retroviruses, this would not be evidence for the theory of evolution.

For a clearer explanation, still in lay terms, see What is the "case for common descent" from ERVs? 

ERVs are Functional

If ERVs are found to have function, they would be highly unlikely to have come from retroviruses. It’s hard to think that viral DNA could be injected into an ape’s genome and somehow be functional. Evidence has surfaced that they do have function.

The evidence for common descent does not depend the notion that ERVs have no function. This is a very common creationist straw man version of the case for common descent from ERVs. It is a dishonest “argument” whose sole function is to give other creationist readers the false impression that they can stop worrying about ERVs.

The idea that they would be highly unlikely to have come from retroviruses because of function is an unsupported assertion, merely being an example of the fallacy of the argument from personal incredulity.

The evidence is that parts of some ERVs serve functions for the host organism. None of this evidence has been uncovered by creationist “research” “institutes”, but by real scientists doing real science. So much for the conspiracy theory that “evolutionists” are suppressing the truth!  ERVs consist of many components. ERV components are also implicated in diseases, especially cancers. A complete, working ERV is a fully functioning disease agent. That’s the last thing everyone wants in every single nuclear cell in their body! 

“We report the existence of 51,197 ERV-derived promoter sequences that initiate transcription within the human genome, including 1,743 cases where transcription is initiated from ERV sequences that are located in gene proximal promoter or 5’ untranslated regions (UTRs).”^[1]“Now it appears that another level of evolution occurs that is not driven by point mutations. Instead, retroviruses insert DNA sequences and rearrange the genome, which leads to changes in gene regulation and expression. If such a change in gene regulation is beneficial, it is passed onto future generations.”^[2]

The previous quote is very telling. There are tens of thousands of ERVs in human and chimp genomes. Does this mean that all are beneficial?

“Our analysis revealed that retroviral sequences in the human genome encode tens-of-thousands of active promoters; transcribed ERV sequences correspond to 1.16% of the human genome sequence ... and PET tags that capture transcripts initiated from ERVs cover 22.4% of the genome.”^[3]

As we can see, it has been discovered that ERVs aid transcription in one fifth of the human genome.

“The ancient retroviruses ... helped a gene called p53 become an important “master gene regulator” in primates. ...the UCSC team gathered compelling evidence that retroviruses helped out. ERVs jumped into new positions throughout the human genome and spread numerous copies of repetitive DNA sequences that allowed p53 to regulate many other genes, the team contends. ... Thus, p53 was crowned “guardian of the genome,” as biologists now call it. Its job is to coordinate the surveillance system that monitors the well-being of cells. Indeed, p53 is so important that when it fails, cancer often results. About half of all human tumors contain a mutated or defective p53 gene.”^[4]

“W"verdana" e report that human ERVs actively shape the p53 transcriptional network in a species-specific manner ... At least one ERV insertion likely reshaped the transcriptional landscape of its surrounding genomic area and was instrumental in creating a new gene that became part of the human-specific p53 regulatory network ... We discovered a unique distribution pattern of p53 sites within repetitive sequences of the human genome, and several ERV families emerged as being substantially enriched for p53 sites in their LTRs.” ^[5]

“Taken together, our findings suggest that HERVs behave like normal cellular genes and are a permanent component of the transcriptome of a cell.”^[6]

One scientist said about junk DNA, of which ERVs are all part:

“The failure to recognize the full implications of this - particularly the possibility that the intervening noncoding sequences may be transmitting parallel information ... may well go down as one of the biggest mistakes in the history of molecular biology.”^[7]

ERVs are important in much of the genome. Does that means ERVs absolutely didn’t come from retroviruses? No, but there are certainly some questions evolutionists need to answer.


Answers: 

Retroviruses replicate by integrating a DNA version of their genomes (called a provirus)  into host DNA. The provirus consists of several genes, all of them oriented to the retroviral replication cycle. But these genes are useless to the process unless they are transcribed back into RNA by the host. This is why retroviral genomes also include transcription promoters. Retroviral promoters are called Long Term Repeats, or LTRs. They are very powerful and indiscriminate promoters likely to promote some “native” DNA as well as retroviral genes - the retrovirus doesn’t “care”. There are many “solo LTRs” which can be understood as remnants of mutational and recombination events in the genome. Drop an LTR at random into a hosts genome, and there is a good chance it will promote something. Just as with more conventionally understood mutations, some of these will be harmful, some will have little or no effect, and some will be beneficial. As these are heritable, good old natural selection will go to work on them in the population, those being harmful getting flushed out of the gene-pool, and those being advantageous will increase in frequency in the gene pool, generation by generation.

We do know that ERVs come from retroviruses. Among the items of evidence for this are: 

The detailed structure of complete ERVs is the same as a retroviral provirus, including all the components required for a retroviral replication cycle.

ERVs exhibit a retroviral, not a host, codon bias.

Functioning retroviruses have been recovered from ERVs.

KoRV is a retrovirus among Koalas, observed in the process of becoming endogenous!

Apoptosis

Apoptosis is a process of the body that kills dangerous cells. Foreign DNA injected into a cell by a virus would surely trigger the cell to commit suicide (apoptosis). So if tens of thousands of ERVs were really introduced by retroviruses, we should expect apoptosis to have ridden most of them long ago. The fact that we have so many ERVs indicates they could not have been injected by retroviruses – apoptosis should have ridden most of the cells.

“Apoptosis, or programmed cell death, is a normal component of the development and health of multicellular organisms. Cells die in response to a variety of stimuli and during apoptosis they do so in a controlled, regulated fashion. The latter occurs when T-cells recognize damaged or virus infected cells and initiate apoptosis in order to prevent damaged cells from becoming neoplastic (cancerous) or virus-infected cells from spreading the infection.”^[8]

Because apoptosis would kill most ERV-containing cells, why is it that we still have so many ERVs hundreds of thousands of years after supposedly being inserted by retroviruses?

*Answers. 

Retroviruses are known to possess apoptosis inhibitors.

Reverse transcription (the rewriting of the RNA genome into DNA) is an error-prone business. ERVs are failed retroviruses (or rather, the descendants of failed retroviruses). One of the things they have failed at is succumbing to apoptosis.

If apoptosis was 100% efficient, all retroviruses would be extinct.

Retroviral infection is a fast, massively parallel process. If apoptosis had removed “tens of thousands” of proviruses, it would also have failed to remove large numbers of them.

Now, evolutionists might ask why the positioning of human ERVs are so similar to the positioning of chimp ERVs if viruses didn’t put them in the common ancestor? The answer seems to be in the overall similarity of the human and chimp genomes: since our DNA is fairly similar^{[9, 10, 11]} to chimps, we’d expect most ERVs should be in similar spots.

So.. ERVs are in similar positions because they are in similar positions?

Similar ERVs in Unrelated Organisms

Another problem for the evolutionary explanation is that very similar ERVs exist in unrelated animals.

“We have sequenced and characterized an endogenous type D retrovirus, which we have named TvERV(D), from the genome of an Australian marsupial, the common brushtail possum (Trichosurus vulpecula). Intact TvERV(D) gag, pro, pol, and env open reading frames were detected in the possum genome. TvERV(D) was classified as a type D retrovirus, most closely related to those of Old World monkeys, New World monkeys, and mice, based on phylogenetic analyses and genetic organization.”^[13]

“For instance gamma-retrovirus was isolated from trophoblastic cells of the baboon placenta. This virus was found to be very closely related antigenically and by sequence homology to the endogenous RD114 virus in cats (which is itself unrelated to endogenous FeLV). Benveniste and Todaro observed, like we did for jungle fowl, that only certain species of the cat genus, Felis, possessed this endogenous genome related to the baboon ERV. In contrast, all species of baboons carry this virus so it would appear to have been present in the germ line of primates much longer than in cats. Thus it seems evident that a horizontal, infectious event occurred to transfer the virus from baboons to cats, whereupon it became endogenous in the new species.”^[14]

How do the authors “explain” this?

“Since cats would be quite likely to scavenge and feed on baboon placentae, a possible exposure to the virus can be envisioned.”^[14]

This is hopeful imagination at best!

I don’t understand the writer’s difficulty here. ERVs in different locations in the DNA of different species indicate separate endogenization events. Retroviruses are known to be capable of “jumping” species. That they will endogenize separately in separate species is not unsurprising. (“Endogenize” means entering germ-line cells and becoming heritable.)

More Problems

It is interesting to note that ERVs are different than the retroviral genomes from which they are supposed to have originated. Evolutionists usually explain this away by claiming that the ERV sequences have evolved to the point where they are quite different from their ancestral genomes. If this is so, then there is consequently very little to lead us to the conclusion that ERVs are derived from retroviruses.

The writer fails to provide any instances of this, so no further comment is necessary.

If ERVs really are a product of retroviruses, how could they have been inserted into reproductive cells thousands of times without fatal damage to the host? Having healthy and strong reproductive cells is mandatory to produce a viable zygote, so why would viral-infected reproductive cells be considered more fit than ones without ERVs? Furthermore, how could they survive for hundreds of thousands of years in two different species?

They do do fatal damage, most of the time. But as has been mentioned before, reverse transcription is error-prone. With respect to ERVs that provide an adaptive advantage, we are talking about mutants that fail as retroviruses, but may survive within the host genome, especially when they provide an adaptive advantage. 

Changes to the reproductive cells are rare and often harm the animal. So why should we believe that ERVs were inserted many thousands of times?

Different retroviruses were integrated on different occasions. Each time, the harmful ERVs would become extinct, along with their carriers and the neutral and specially the advantageous ERVs will persist - along with their carriers.

“In short, the notion that molecules of germ cells ... are in states of perpetual change is not, in our present understanding of cell biology, tenable. This doesn’t mean that “molecular change” does not occur; only that mechanisms provoking such change in germ cells are likely instantaneous and stochastic and probably often lethal (Maresca and Schwartz 2006) — which will preclude their persistence into future generations.”^[15]

How could it be that unrelated ERVs in different species created essentially the same gene?

If the author is talking about syncytins here, all retroviruses possess an env (environment) gene. These are the genes that have been exapted as syncytins.

“ERVWE1/Syncytin-1 and ERVFRDE1/Syncytin-2 are specific to primates and thus do not exist in other placentae. However, this apparent endogenous retrovirus hijacking for placentation use is not restricted to the primates. Indeed two unique endogenous envelope genes of retroviral origin have been found in the mouse, i.e. Syncytin-A and –B ... Altogether the data strongly argue for convergent evolution of endogenous retroviral envelopes to serve for placentation in mammals.”^[16]

One may argue that convergent evolution is the answer, as the author did, but this explanation has no real scientific basis. Convergent evolution is only ever used to explain similarities between organisms that are otherwise unrelated. But then why shouldn’t we consign other ‘proof-of-evolution’ similarities to convergent evolution?

Well, this is certainly not a case of same design, same designer! The evidence from ERVs is not a matter of general similarity, but of precisely commonly located genetic markers that are clearly of retroviral origin, and whose commonality can only be explained by common ancestry.

Conclusion

In summary, a strong case can be made pointing to the view that ERVs were not inserted by retroviruses. They have function, should have been ridden by apoptosis, are different than their ancestral genomes, and it is incredible that the organisms did not die after being infected with so many viral genes. With so many problems, a lot of explaining must be done before using ERVs as evidence for evolution.

Function is a straw-man. Why should remnants of viral infections be recycled by evolution any less than other sources of variation? In fact, one could argue that complete but mutated versions of promoters and genes should be exapted more readily than having to be built from scratch.

Possible Responses

1. “The article said ERVs couldn’t be injected by viruses and be functional. No, ERVs evolved their functions later.”
   But this is the very point in question. Sequences inserted by harmful viruses virtually never become beneficial functioning pieces of DNA. To say that they “just evolved” is ad hoc.
   Of great interest is the fact that genetic recombination (or the like) has not been observed to change ERVs

   “The question arises as to whether HERV elements can continue to change our genomic landscape through active retrotransposition or recombination events. While no direct evidence indicates that such events are ongoing in the human genome, members of the HERV-K family appear to be the most likely candidates for playing such a role.” ^[17]

   “Although repeated sequence elements such as HERVs have the potential to lead to chromosomal rearrangement through homologous recombination between distant loci, evidence for the generality of this process is lacking.”^[18]

   “As for the elimination of the numerous copies produced by such rapid and extensive bursts, it is not yet clear whether recombination occurs continuously through time, thus slowly and regularly decreasing large amounts of DNA, or if there is any mechanism that would activate large recombination events following bursts of amplification, as proposed by some authors (Rabinowicz 2000).”^[19]

2. “The article asked us how harmful ERVs could survive for hundreds of thousands of years in two different species when reproductive cells won’t tolerate this. Answer: they evolved so that they were not harmful.”
   This answer does not explain the problem. It would take many, many years for ERVs to evolve, whereas the animal/zygote would be killed immediately when these ERVs hadn’t yet evolved...

I repeat: Reverse transcription is error prone. ERVs are the descendants of faulty (from the PoV of the retrovirus) integrations. Recombination does happen, but this is not the “explanation” for organisms surviving endogenization events.In the following reference section, unlike the original author, I provide links to the cited articles wherever possible. This is so you can conveniently evaluate the literature for yourselves, rather than being tempted to rely on his/her particular spin.References

1. Conley, A.B., Piriyapongsa, J. and Jordan, I.K., “Retroviral promoters in the human genome,” Bioinformatics 24(14):1563, 2008.
2. “Ancient Retroviruses Spurred Evolution Of Gene Regulatory Networks In Humans And Other Primates,” ScienceDaily, University of California - Santa Cruz, Nov. 15, 2007. http://www.physorg.com/news114266805.html Back to text
3. Conley, A.B., Piriyapongsa, J. and Jordan, I.K., Reference 1. 
4. “Ancient Retroviruses Spurred Evolution Of Gene Regulatory Networks In Humans And Other Primates,” ScienceDaily, University of California - Santa Cruz, Nov. 15, 2007. http://www.physorg.com/news114266805.html 
5. Ting Wang, Jue Zeng, Craig B. Lowe, Robert G. Sellers, Sofie R. Salama, Min Yang, Shawn M. Burgess, Rainer K. Brachmann, and David Haussler, edited by Eric H. Davidson, “Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53,” PNAS, November 20, 2007 vol. 104 no. 47 18613-18618. http://www.pnas.org/cgi/content/full/104/47/18613 
6. Wolfgang Seifarth, Oliver Frank, Udo Zeilfelder, Birgit Spiess, Alex D. Greenwood, Rüdiger Hehlmann, and Christine Leib-Mösch (author contributions), “Comprehensive Analysis of Human Endogenous Retrovirus Transcriptional Activity in Human Tissues with a Retrovirus-Specific Microarray,” Journal of Virology, January 2005 vol. 79 no. 1 341-352. http://jvi.asm.org/cgi/content/full/79/1/341 
7. Mattick, J., cited in: Gibbs, W.W., “The Unseen Genome: Gems Among the Junk,” Scientific American, 289(5):26–33, November 2003; pp. 29–30. 
8. Reproductive and Cardiovascular Disease Research Group. http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/ 
9. Nature, May 27, 2004, pp. 382-388.
10. New Scientist News Service 23 September 2002. 
11. The Washington Post, Monday, September 30, 2002, A7.
13. Gregory J. Baillie and Richard J. Wilkins, “Endogenous Type D Retrovirus in a Marsupial, the Common Brushtail Possum (Trichosurus vulpecula),” Journal of Virology, March 2001 vol. 75 no. 5 2499-2507. http://jvi.asm.org/cgi/content/full/75/5/2499
14. Robin A Weiss, “The discovery of endogenous retroviruses,” Retrovirology, 2006; 3: 67. Published online 2006 October 3. doi: 10.1186/1742-4690-3-67. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1617120 
15. http://www.mitpressjournals.org/doi/abs/10.1162/biot.2006.1.4.357 
16. Gimenez J, Mallet F., “ERVWE1 (Endogenous Retroviral family W, Env(C7), member 1),”Atlas Genet Cytogenet Oncol Haematol, September 2007. http://AtlasGeneticsOncology.org/Genes/ERVWE1ID40497ch7q21.html
17. Jennifer F. Hughes and John M. Coffin, “Human Endogenous Retroviral Elements as Indicators of Ectopic Recombination Events in the Primate Genome,” Genetics, November 2005 vol. 171 no. 3 1183-1194. http://www.genetics.org/cgi/content/full/171/3/1183 
18. Hughes JF, Coffin JM, “Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution,” Nature Genetics, 2001 Dec;29(4):487-9. http://www.ncbi.nlm.nih.gov/pubmed/11704760?ordinalpos=1&itool=EntrezSystem2PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus
19. C. Vitte and O. Panaud, “Formation of Solo-LTRs Through Unequal Homologous Recombination Counterbalances Amplifications of LTR Retrotransposons in Rice Oryza sativa L.,” Molecular Biology and Evolution (2003) 20 (4): 528-540. First published online: March 5, 2003. http://mbe.oxfordjournals.org/cgi/content/full/20/4/528