Function Of Ervs
Posted 25 March 2010 - 10:49 PM
Endogenous retroviruses or "ERVs" are viral elements that are thought to have inserted themselves into the genomes of various creatures - to include humans and apes. ERVs are thought by many to be among the strongest evidences supporting the theory of common descent. For example, it is argued that the same ERVs in the same locations in the genomes of both humans and apes are best explained by a shared common ancestry between humans and apes. In other words, the common ancestor of humans and apes must have been the one to initially experience the ERV insertion into its genome. Then, later, when human and ape ancestors split off from this common ancestral lineage, the same ERV sequences were maintained in the same places in the genomes of both lineages.
This argument seems rather straightforward and even downright obvious at first approximation. However, there are several difficult problems with this theory.
Signs of function:
One problem is that a number of ERVs are being discovered to be functionally beneficial.
The ERV known as enJSRV has been shown to "regulate trophectoderm growth and differentiation in the peri-implantation ovine conceptus. This work supports the hypothesis that ERVs play fundamental roles in placental morphogenesis and mammalian reproduction."
It is also interesting to consider that ERVs and other supposedly "parasitic" DNA elements are found far more often in the genomes of more "complex" organisms - suggesting again that non-coding portions of DNA once thought to be nothing but "junk DNA" and evolutionary remnants are actually playing important functional roles in the genomes of more functionally complex organisms.
"With the accumulation of genomic sequence data, certain unexplained patterns of genome evolution have begun to emerge. One striking observation is the general tendency of genomes of higher organisms to evolve an ever decreasing gene density with higher order. For example, E. Coli has a gene density of about 2 Kb per gene, Drosophila 4 Kb per gene and mammalian about 30 Kb per gene. Much of the decreased density is due to the increase in the accumulation of non-coding or 'parasitic DNA' elements, such as type one and two transposons. Current evolutionary theory does not adequately account for this observation (81). In addition mammals appear to have retained the presence of at least some copies of non-defective 'genomic retroviruses', such as intercysternal A-type particles (IAP's) or endogenous retroviruses (ERVs). It is currently difficult to account for the selective pressure that retains these genomic viruses . . ."
In this same line, a subsequent paper presented evidence that proposes potential reasons for the previously observed "selective pressure" and the actual need for ERVs within the genomes of complex organisms like humans. In the journal Bioinformatics, Conley et. al. write:
"We report the existence of 51,197 ERV-derived promoter sequences that initiate transcription within the human genome, including 1743 cases where transcription is initiated from ERV sequences that are located in gene proximal promoter or 5' untranslated regions (UTRs)...
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. These data suggest that ERVs may regulate human transcription on a large scale."
ERVs are also being shown to be protective against infection by harmful exogenous retroviruses:
"A possible biological role hypothesized for ERVs is to help the host resist infections of pathogenic exogenous retroviruses, affording a selective advantage to the host bearing them. For instance, some avian and murine ERVs can block infection of related exogenous retroviruses at entry by receptor interference; mouse Fv-1 blocks infection at a preintegration step, also can be viewed as an ERV."
ERVs may also aid in modulating the activity of the immune system:
"For example, the HERV-K sequence of the human teratocarcinoma derived virus type (HTDV), is reported to be able to make retrovirus like particle and can express gag, pol and env genes via vectors. Also, ERV 3 can express env gene in embryonic placental tissues. Such reports may now explain the numerous early observations of being able to find viral particles in human tissues. Although some HERV's are expressed in mammary tumors, the feline RD114, ERV-3, and HERV K10+ are all expressed in placental tissues. What then is the significance of nondefective ERVs and why is expression so common in embryos? . . . I and Venables et al. in the Boyd group have proposed that some of these HERV's may function during embryo implantation to help prevent immune recognition by the mother's immune system. . .
In addition, the ERV gag gene product may also be immuno-modulatory. The p70 (gag) of mouse IAP has been cloned and expressed and shown to be identical to IgE binding factor (IgE-BF) which is a regulator of B-cell ability to produce IgH. More recently, it has been reported that endogenous gag is Fv-1, an-Herv.L like endogenous virus which confers resistance to MLV tumors. Although some researchers disagree with the immunomodulatory role of p15E, an immune suppressing activity in culture assays has been clearly established. These supporting results seem sufficiently clear to warrant a serious investigation that both the env and gag gene products of ERV's may modulate immunity."
So, it isn't a necessary default that all ERV-like sequences are functionless evolutionary remnants of random viral infections as originally proposed by prominent evolutionists such as Richard Dawkins or Douglass Theobald. This fact was highlighted by Richard Sternberg in a 2002 issue of Annals of the New York Academy of Sciences in the following statement:
"The selfish DNA narrative and allied frameworks must join the other Ã¢â‚¬ËœiconsÃ¢â‚¬â„¢ of neo-Darwinian evolutionary theory that, despite their variance with empirical evidence, nevertheless persist in the literature."
Similar support for this concept is noted by Dr. Wang from the Haussler lab:
"These results raise new questions about the role of so-called 'junk DNA,' the vast regions of the genome that don't code for proteins. ERVs fall into that category. Many scientists once believed that such DNA served no purpose, but new data from the Haussler lab and other labs are challenging that view."
Origin of ERVs from exogenous retroviruses - or visa versa?:
There is also some evidence that exogenous retroviruses are occasionally derived from ERVs - instead of the other way around.
"Exogenous retroviruses may have originated from ERVs and ERV-Ls in particular may represent an intermediate between retrotransposons and exogenous viruses."
This concept is supported by the observation that there are no known examples of current exogenous retroviral insertions into the modern human genome. Also, there are no known infectious exogenous counterparts of any human endogenous retroviruses known to exist today. This is a very curious finding considering the striking commonality of ERVs within the human and ape genomes if the prevailing hypothesis that these ERV sequences were in fact derived from exogenous infective retroviruses.
Ã¢â‚¬Å“No current transposition activity of HERVs or endogenization of human exogenous retroviruses has been documented so far.Ã¢â‚¬Â
Ã¢â‚¬Å“Most of these elements represent ancient retroviral infections, as evidenced by their wide distribution in primate species, and no infectious counterparts of human endogenous retroviruses (HERVs) are known to exist today.Ã¢â‚¬Â
This opens up the possibility that at sometime in the past all exogenous retroviruses were originally derived from ERVs - - not necessarily the other way around with ERVs originally being derived from exogenous retroviral infections. In other words, it is possible that all sequences that are now thought to be viruses or viral elements were originally derived from functional genetic sequences that have since suffered degenerative changes and loss of genetic controls, resulting in various parasitic features that we see in many viruses today - as well as the resulting harmful effects of this loss of regulation such as tumor development and the association of numerous types of cancers and neoplastic processes.
Non-random viral insertions:
Beyond this, it has also been shown that the insertions of ERVs are not entirely random despite this common belief - even among mainstream scientists. ERVs actually show a preference for certain fairly specific locations in various genomes.
"Although retrovirus integration can occur throughout the genome, local "hot spots" for integration exist where a strong preference for particular sites over others can be demonstrated statistically. Recent work with HIV and murine leukemia virus has implied that there is also a preference for integration into transcribed regions of the host genome, in the case of murine leukemia virus, near transcriptional start sites. The basis for these preferences is unknown, but they may reflect interaction of the pre-integration complex with specific proteins or with specific DNA sequences or structures that are associated with transcription."
"But although this concept of retrovirus selectivity is currently prevailing, practically all genomic regions were reported to be used as primary integration targets, however, with different preferences. There were identified 'hot spots' containing integration sites used up to 280 times more frequently than predicted mathematically."
The odds against similar ERV germline insertions:
In order for an ERV to be in the same location in differing populations via common descent one of two things had to have happened. Either many individuals in the same population were infected by the save virus which inserted itself into the same position in all the different individuals, or there was a very significant population bottleneck where only a very few individuals (like just one individual) were infected and then the offspring of that individual subsequently overtook the entire population. Obviously, if multiple individuals were infected at the same locus/ loci then that would mean a common mechanism is at play.
Next comes meiosis with its chromosomal recombinations being the norm. So, not only do the ERVs have to survive the population bottle-neck they have to stay in place all the while genetic rearrangements are taking place all around. In short, a viral event would have to overtake a majority of the population for each different ERV sequence in the genome (tens of thousands of them), and each ERV would have had to inject itself into gametic cells while not harming the reproductive aspects of the host, then remain in the genome without being removed by random effects of recombination, - - and all of this would have had to happen many times in different species. The odds do not seem all that likely.
The sheer number of ERVs:
In this light it is interesting to note that over 30,000 different ERVs are known within human genome. The range of the total human genome occupied by ERV sequences is anywhere from 1% to 8% - depending upon the reference (with more recent references favoring 8% or greater). The same range is true for the chimp genome as well.41 In fact, more recent work suggests a 45% ERV origin for the human genome at large (Mindell and Meyer 2001) and 50% for mammalian species in general . In any case, of these tens of thousands of recognizable ERVs, only seven are currently known to infect both humans and chimps at identical locations within the separate genomes . Isn't it interesting that out of 30,000 ERVs only 7 of them are known to have inserted at the same site in humans and chimps? - What are the odds given the known preference of many ERVs for fairly specific hot spot insertions? Yet, this is the argument for ERVs being evidence of common descent as per Talk.Origins:
"In humans, endogenous retroviruses occupy about 1% of the genome, in total constituting ~30,000 different retroviruses embedded in each person's genomic DNA (Sverdlov 2000). There are at least seven different known instances of common retrogene insertions between chimps and humans, and this number is sure to grow as both these organism's genomes are sequenced (Bonner et al. 1982; Dangel et al. 1995; Svensson et al. 1995; Kjellman et al. 1999; Lebedev et al. 2000; Sverdlov 2000). Figure 4.4.1 shows a phylogenetic tree of several primates, including humans, from a recent study which identified numerous shared endogenous retroviruses in the genomes of these primates (Lebedev et al. 2000). The arrows designate the relative insertion times of the viral DNA into the host genome. All branches after the insertion point (to the right) carry that retroviral DNA - a reflection of the fact that once a retrovirus has inserted into the germ-line DNA of a given organism, it will be inherited by all descendents of that organism." ( Link - last accessed 3/10/09)
Another interesting aspect of ERVs is that they do not always show the expected evolutionary pattern of "inheritance". According to the proposed phylogenetic tree (shown to the right) chimps are closer to humans than to gorillas. Given this scenario, gorillas and chimps would only be expected to share an ERV if this same ERV were also present in humans. However there are some ERVs that don't seem to fit this pattern. For example, the K family of ERVs (HERV-K provirus) is present in chimps and gorillas, but not in humans. Also, portions of ERVs known as CERV 2 and CERV 1 elements are present in chimpanzee, bonobo and gorilla (non-orthologous) but are absent in human, orangutan, old world monkeys, new world monkeys.
The usual explanation for such findings, of course, is that humans lost this or that particular ERV along the way. Of course, this post-hoc argument could be used to explain any aberrancy. Given that there are only 7 known ERVs that are shared, among tens of thousands, it is somewhat problematic that there are at least a few that are known to contradict the predicted phylogeny. It is also interesting that an entire human population could loose an ERV that is preserved in both chimps and gorillas. This would require yet another extreme population bottleneck to explain.
There are also other even more problematic phylogenetic inconsistencies with ERVs:
"We performed two analyses to determine whether these 12 shared map intervals might indeed be orthologous. First, we examined the distribution of shared sites between species. We found that the distribution is inconsistent with the generally accepted phylogeny of catarrhine primates. This is particularly relevant for the human/great ape lineage. For example, only one interval is shared by gorilla and chimpanzee; however, two intervals are shared by gorilla and baboon; while three intervals are apparently shared by macaque and chimpanzee. Our Southern analysis shows that human and orangutan completely lack PTERV1 sequence. If these sites were truly orthologous and, thus, ancestral in the human/ape ancestor, it would require that at least six of these sites were deleted in the human lineage. Moreover, the same exact six sites would also have had to have been deleted in the orangutan lineage if the generally accepted phylogeny is correct. Such a series of independent deletion events at the same precise locations in the genome is unlikely. . .
"Several lines of evidence indicate that chimpanzee and gorilla PTERV1 copies arose from an exogenous source. First, there is virtually no overlap (less than 4%) between the location of insertions among chimpanzee, gorilla, macaque, and baboon, making it unlikely that endogenous copies existed in a common ancestor and then became subsequently deleted in the human lineage and orangutan lineage. Second, the PTERV1 phylogenetic tree is inconsistent with the generally accepted species tree for primates, suggesting a horizontal transmission as opposed to a vertical transmission from a common ape ancestor. An alternative explanation may be that the primate phylogeny is grossly incorrect, as has been proposed by a minority of anthropologists." [emphasis added]
"Inconsistencies do exist with phylogenetic analyses and are often explained by ad hoc arguments without positive evidence."
In fact, it seems like just about any finding or data set can be explained within the evolutionary paradigm using this or that "ad hoc" explanation to make the data fit the theory. This produces a problem of bias when it comes to interpreting data sets. Such biases in the interpretation of ERV phylogenies have been recognized for some time now. For example, according to Posada and Crandal, in a 2001 paper published in Molecular Biology and Evolution:
"Wrong models of [ERV] evolution lead to the estimation of trees that are in agreement with biochemical and immunological evidence and with previous phylogenetic studies. . .
When examining the results of the present study, only those trees estimated according to simple, likely wrong, models of evolution agree with current evidence. In most of the reconstructed trees, different genera appear as monophyletic groups. These groups have normally high bootstrap values indicating that, given the data sets at hand, we can be confident in the nodes defining these clusters. When more complex, more realistic, models of evolution are employed, fewer genera are recovered as monophyletic, the level of support is lower, and the topologies are very different from the assumed "known" trees.
Phylogenetic bias, by which "incorrect" models can give "correct" answers, has been identified in simulation studies. Why this bias occurs is a question that remains unsolved. . .
One possible factor contributing to the bias is most likely a problematic alignment, in which sequences belonging to the same group (genus) are easily aligned, whereas the opposite is true for sequences belonging to different groups. Complex models might be confounded when trying to extract information from the bad intragroup sequence alignment, while simpler models use basically the observed patterns. This would warrant a word of caution for the estimation of phylogenies from highly divergent data sets."
To summarize, evolutionists usually gloss over at least a few important facts when discussing the topic of ERVs. Many retroviruses can infect both humans and apes. The most notable of these is HIV, which is widely believed to have originated as SIV in chimpanzees, but can also infect humans, apes, and monkeys. It is entirely possible, therefore, that humans and apes were independently infected with the same virus given so many different ERVs and the similarity of the human and ape genomes.
Also, some retroviruses have been shown to have highly targeted insertion points, meaning that the virus selects very specific segments of the genome for insertion. Consequently, it is entirely possible that the same virus infected both humans and apes, and targeted the same location. This seems especially plausible in light of the fact that humans and apes have tens of thousands of endogenous retroviruses in their respective genomes. In other words, given so many thousands of different types of ERVs all targeting fairly specific locations, it is actually likely that at least a few of these retroviruses will infect both humans and apes at the very same location within the respective genomes without any need to invoke the common descent hypothesis.
To add to this, the theory that retroviral insertions are conclusive phylogenetic markers has been falsified by studies that have shown that, "Although independent insertions at the same locus may be rare [viral] insertions are not homoplasty-free phylogenetic markers". This would seem to be especially true given so many known ERV insertions that are at least generally targeted.
Additionally, some endogenous retroviruses are now known to be functionally indispensable - i.e., they are actually functionally beneficial and even vital to species' survival. If a particular retrovirus is functionally advantageous, that would only add to the plausibility of how a retrovirus can spread to the entire species without the need for common descent or dramatic population bottlenecks. It also presents the possibility that retroviruses were used as part of the original creative process; as retroviruses are often used in genetic engineering today, to introduce new genetic material to cells or aid in the transportation of genetic information.
See also the following excellent Review Article on ERVs.
Posted 26 March 2010 - 12:27 AM
Posted 26 March 2010 - 07:04 AM
It is great article. The section about epigentics is a very worth while read. Epigentics is going to change how we view biology and evolution. It really changes everything.
0 user(s) are reading this topic
0 members, 0 guests, 0 anonymous users