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Endogenous retroviruses

Loudmouth

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h2whoa said:
Ah. Yes. Well. Ahem.

It would be hypocritical of me if I didn't admit when I was wrong. You are quite right. I had got my wires crossed on this point. I thought I remembered something from my virology studies but when I came to look over the notes I couldn't find it. I emailed the Professor who had taught me virology and he confirmed that I must have been having a schizoid episode!

Game, set and match, Loudmouth!

h2
Very gracious of you, h2. When I first encountered this argument I heard creationists stating that the separate infections by the same virus could explain commonalities in ERV's. I took their argument at face value and dug into the primary literature. I found that the creationist arguments lacked evidence, and were in fact falsified by the data. The paper that I referenced in previous posts (the one with the figure showing the insertions) found about 500 integration sites for HIV in peripheral blood mononuclear cells. Each one of these integration sites was about 100-250 kb with an integration rate of 75% in those integration sites. If we take an average of 150 kb for each site, this means that there are about 75 million bases open to integration out of a 3 billion base genome. That would mean that the chances of two ERV's occuring at the same base due to separate integrations would be 1 in 75 million. Other RV's show the same amount of dispersal and probabilities. The data just does not support the creationist argument.
 
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joelazcr

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Comparisons of ERV insertions between species is not done at the
nucleotide level, but at orthologous positions, assuming the species
have a common ancestor.

The talkorigins reference to "identical chromosomal locations" is
very misleading.

http://www.talkorigins.org/faqs/comdesc/section4.html#retroviruses

Figure 4.4.1. Human endogenous retrovirus K (HERV-K) insertions in identical chromosomal locations in various primates (Reprinted from Lebedev et al. 2000, © 2000, with permission from Elsevier Science).

This is the article referenced:

Lebedev, Y. B., Belonovitch, O. S., Zybrova, N. V, Khil, P. P., Kurdyukov, S. G., Vinogradova, T. V., Hunsmann, G., and Sverdlov, E. D. (2000) "Differences in HERV-K LTR insertions in orthologous loci of humans and great apes." Gene 247: 265-277.

If you look at the figure referenced in the source article, the
caption is completely different. Actually the article never mentions anything about "identical chromosomal locations"

Here is the caption in the article:

Fig. 5. Subfamilies and branches of HERV-K LTRs. Arrows supplied with the corresponding branch names indicate estimated ages of propagation starts. Dotted squares and open circles at the ends of the arrows designate LTR-I and LTR-II subfamilies respectively. An evolutionary tree of the primate lineage is presented at the bottom of the figure. Arrows at the tree mark the times of the LTR insertions in the loci; loci names are added at the arrow tops; dark and light arrows designate LTRs belonging to the LTR-I and LTR-II subfamilies respectively.

The article below describes these comparisons on a much more
general level:

Sverdlov, E. D. (2000) "Retroviruses and primate evolution." BioEssays 22: 161-171

"HERVs are different in their sequences and can be
grouped according to sequence similarities, but the various
systems of HERV classification are rather confusing
and no one is universally accepted. The classi-
fications are principally based on sequence homologies to
exogenous retroviruses or preexisting ERVs, or on the
type of reverse transcriptase putative primer binding sites
(PBS). Briefly, HERVs can be classified into two broad
groups: class I including HERVs related to mammalian
exogenous type C retroviruses, and class II comprising all
HERVs related to retroviruses of mammalian A, B and D
types, and avian type C. The mutation rate of the exogenously
replicating retroviruses is at least 104 times higher
than that of a typical cellular gene or integrated endogenous
retroviruses, hence finding extensive stretches
of homologous sequence between endogenous retrovirus
sequences and currently existing strains of replicating
retroviruses is unlikely. Therefore, a classification based
on the type of PBS located close to the LTRs is probably
more reliable. By this method, HERVs can be divided into
groups designated as HERV-E, HERV-H, HERV-I,
HERV-K, HERV-L, HERV-R, etc., following the one-letter
code for the amino acid transferred by the priming tRNA."

"The majority of HERVs have been altered, for instance
truncated or mutated in such a way that they have lost the
ability to produce fully functional proteins. Some of the
HERVs, however, are transcriptionally active and code for
viral proteins that even form retrovirus-like particles.
The LTRs that flank proviruses in the genome have frequently
recombined, leading to the accumulation of tens of
thousands of solitary HERV LTRs with no retroviral genes
attached."

Using the phrase "identical chromosomal locations" just does not
fit the methods of comparison.
 
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J

Jet Black

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joelazcr said:
Comparisons of ERV insertions between species is not done at the
nucleotide level, but at orthologous positions, assuming the species
have a common ancestor.

The talkorigins reference to "identical chromosomal locations" is
very misleading.

http://www.talkorigins.org/faqs/comdesc/section4.html#retroviruses

Figure 4.4.1. Human endogenous retrovirus K (HERV-K) insertions in identical chromosomal locations in various primates (Reprinted from Lebedev et al. 2000, © 2000, with permission from Elsevier Science).

This is the article referenced:

Lebedev, Y. B., Belonovitch, O. S., Zybrova, N. V, Khil, P. P., Kurdyukov, S. G., Vinogradova, T. V., Hunsmann, G., and Sverdlov, E. D. (2000) "Differences in HERV-K LTR insertions in orthologous loci of humans and great apes." Gene 247: 265-277.

If you look at the figure referenced in the source article, the
caption is completely different. Actually the article never mentions anything about "identical chromosomal locations"

Here is the caption in the article:

Fig. 5. Subfamilies and branches of HERV-K LTRs. Arrows supplied with the corresponding branch names indicate estimated ages of propagation starts. Dotted squares and open circles at the ends of the arrows designate LTR-I and LTR-II subfamilies respectively. An evolutionary tree of the primate lineage is presented at the bottom of the figure. Arrows at the tree mark the times of the LTR insertions in the loci; loci names are added at the arrow tops; dark and light arrows designate LTRs belonging to the LTR-I and LTR-II subfamilies respectively.

The article below describes these comparisons on a much more
general level:

Sverdlov, E. D. (2000) "Retroviruses and primate evolution." BioEssays 22: 161-171

"HERVs are different in their sequences and can be
grouped according to sequence similarities, but the various
systems of HERV classification are rather confusing
and no one is universally accepted. The classi-
fications are principally based on sequence homologies to
exogenous retroviruses or preexisting ERVs, or on the
type of reverse transcriptase putative primer binding sites
(PBS). Briefly, HERVs can be classified into two broad
groups: class I including HERVs related to mammalian
exogenous type C retroviruses, and class II comprising all
HERVs related to retroviruses of mammalian A, B and D
types, and avian type C. The mutation rate of the exogenously
replicating retroviruses is at least 104 times higher
than that of a typical cellular gene or integrated endogenous
retroviruses, hence finding extensive stretches
of homologous sequence between endogenous retrovirus
sequences and currently existing strains of replicating
retroviruses is unlikely. Therefore, a classification based
on the type of PBS located close to the LTRs is probably
more reliable. By this method, HERVs can be divided into
groups designated as HERV-E, HERV-H, HERV-I,
HERV-K, HERV-L, HERV-R, etc., following the one-letter
code for the amino acid transferred by the priming tRNA."

"The majority of HERVs have been altered, for instance
truncated or mutated in such a way that they have lost the
ability to produce fully functional proteins. Some of the
HERVs, however, are transcriptionally active and code for
viral proteins that even form retrovirus-like particles.
The LTRs that flank proviruses in the genome have frequently
recombined, leading to the accumulation of tens of
thousands of solitary HERV LTRs with no retroviral genes
attached."

Using the phrase "identical chromosomal locations" just does not
fit the methods of comparison.


post that as feedback to talkorigins then. Odds are it will get answered.
 
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kbombbilly

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I have a few questions about ERVs.
1) How do we identify ERVs? Is it simply by finding the LTRs, or is there more to it than that?
2) The ERVs that we share with other primates - do we find variations from one individual to another or one species to another? In other words, are they well conserved or do we see a good deal of mutation going on?
3) If HERVs differ from individual to individual - if there are HERVs that aren't common to all humans - do we also find this among chimps and gorillas?
Thanks.
 
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kbombbilly said:
I have a few questions about ERVs.
1) How do we identify ERVs? Is it simply by finding the LTRs, or is there more to it than that?
2) The ERVs that we share with other primates - do we find variations from one individual to another or one species to another? In other words, are they well conserved or do we see a good deal of mutation going on?
3) If HERVs differ from individual to individual - if there are HERVs that aren't common to all humans - do we also find this among chimps and gorillas?
Thanks.

1. We know what we're looking for. Viral genomes are short and easy to sequence and decode. We know, for instance, the gene that codes for reverse transcriptase (something only retrovirae use), so when we find that in, say, a human, we have a good hunch it's an ERV. They also look for viral gene fragments and, yes, LTRs.

2. Things are generally well conserved. We have a very good method for correcting mutations -- even in genes that aren't our own! There may be a few small discrepancies, but if there are so many that they cannot definitely call it a viral gene, then they simply don't count the ERV. There are more than enough pristine ones to make up for it. :D

3. I am not sure, but I imagine so. Since my father may have received and passed on an ERV to me in his own lifetime that you would not have, I see no reason why it shouldn't be applicable in all cases.
 
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Novaknight1

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WinAce said:
Nice find! Here's a bit more information:

ERVs, a startling line of evidence from genetics (not fossils) provides additional, overwhelming support for human/chimp common ancestry, one that establishes it beyond a shadow of a doubt.

Much like stellar parallax could be considered 'proof' of heliocentricism, so too do unique fingerprints of ancient retroviral infection demonstrate relatedness if found in the genome of two different organisms.

1. Background

Viral infections. We all know and hate them. From the common cold to the common cold sore, they're annoying little buggers. The virus particle invades a cell, injects its proprietary genome, hijacks the cellular machinery and turns it into a virus-making factory. Upon successful completion of this process, the cell begins releasing fresh copies of the virus, often by bursting and dying.

Occasionally, however, something goes wrong in the integration process. When this occurs, the cell can survive, but selected portions of the viral DNA remain in its genome. These vary from infection to infection, not just from virus to virus.

In effect, the cell becomes permanently scarred and carries the unique, identifiable fingerprint of its assailant. (Source)

Since the markers are now in the genome, they become hereditary--hence, any descendant of the afflicted cell will contain the same exact viral fingerprint(s) at the same exact spot in its DNA.

Viral infections are, of course, not limited to the mucous membranes, blood stream and lungs. Under certain conditions, they can also infect a germ line (egg or sperm) cell. The odds of this cell now surviving to adulthood are astronomically low; not only does it have to survive a viral infection, but be one of the extremely lucky few that ever make it to merge with their counterpart and form a viable zygote.

However, this does occur. When it does, the resulting offspring has the unique viral fingerprint embedded in every cell in its body, what is known as an "endogenous retroviral insertion", henceforth referred to as an ERV. (Source)

ERVs can be easily identified by their extreme similarity to known retroviruses. They even contain vestiges of gag, env and pol genes that code for viral surface proteins (explanation of GEP protein coats, information on their presence in ERVs).

We've directly observed creation of new, identifiable ERVs by viral integration into cells in vitro, as well, so this process is as well-documented (if not more) as fossil formation. When it occurs in ordinary cells, it can cripple vital genes, subsequently causing cancer. High-risk papillomaviruses have been indicted as one of the leading causes of cervical tumors, for example. (Source)

Like any genes, the viral elements can then piggyback on the success of an individual and become established in the entire species. In small populations, this can easily occur via genetic drift (random establishment of selectively neutral or deleterious alleles). In larger ones, natural selection can work to establish the few ERVs that yield a benefit to their host.

Each step in the process is not very common, and has unique aspects that are extremely unlikely to be reproduced in two independent cases of ERV creation. Hence, when they all occur, the organisms possessing the ERV are marked with a molecular fossil that will prove indispensible in tracing their origin.

2. Evolutionary Implications of ERVs

In a nutshell, this can serve as a "paternity test" of sorts: if you find the same endogenous retroviral insertion in two different organisms, the only viable explanation is that they inherited same from a common ancestor that, itself, possessed it. Offshoot species will have the same unlikely and easily identifiable ERVs, enabling us to construct accurate phylogenies from an independent line of evidence.

retrovirus.gif

Human endogenous retroviral insertions in identical chromosomal locations in various primates. Notice just how well the standard evolutionary phylogeny, derived from fossil and anatomical evidence (humans and chimps closest, then orangutans and gorillas, then gibbons, then old world monkeys, then new world monkeys) is corroborated by this uniquely independent line of evidence.(Source)

As a side note, ERVs have also been used to reconstruct the relationships between dogs, jackals, wolves and foxes, among other species of domestic animal.

Needless to say, this offers a quick and easy way to experimentally test if any two similar organisms are unrelated. If they are, they won't share any ERVs. If you find the same one at the same place in their genomes, however, the hypothesis they originated independently is effectively falsified.

Due to the nature of the branching tree of life, ERVs shared between distantly-related organisms will have made their initial appearance in their common ancestor. Hence, they would have also been present as further, closer organisms split off from the lineage; if you find an ERV common to humans and monkeys, the ancestor of chimps must have had the insertion as well. Similarly, ERVs found in New World Monkeys and chimps will usually be present in humans. ERVs found in humans and gorillas should be found in chimps. And so on. This provides an additional way to test evolutionary predictions.

It should be noted that there are rare but observable genetic phenomena that can remove ERVs from the genome. However, we can almost always tell when this has occured, such as identifying the characteristic fingerprint of a deletion mutation right before the ERV 'should have' been found.

Nevertheless, the more basic question of 'are there shared ERVs between these species at all?' is a much more stringent, rock-solid test of evolution than the specific phylogenetic relationships individual insertions indicate, which can be erroneous on occasion.

When analyzed as a statistical whole, ERV insertion patterns will also recapitulate phylogenies drawn from independent data like the fossil record and comparative anatomy. This is a remarkable confirmation, and totally at odds with the predictions made by the hypothesis of independent origin of species.

As you can see by now, this is the strongest support for evolution I've ever come across; a truly powerful and damning smoking gun.

Lol. How come ape DNA is only 86.5% similar to human DNA?

http://www.whyevolution.com/chimps.html
 
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Tomk80

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Novaknight1 said:
So you think that something that makes Evolution A DUD is irrelevant?
How does it make evolution a dud? As long as genetics reflects the twin-nested hierarchy, common ancestry stands. The amount of similarity in itself does nothing for this argument. In fact, on it's own it gives very little information.
 
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mark kennedy

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I didn't know about the invitation and I have only recently developed an interest in the subject. Since the subject of ERVs keeps coming up I think it makes sense to take another look at it. I especially liked the post by Winace (sp?) early in the thread which is why I bumped the thread. At any rate, while we are clearing up this buisness of ERVs I think we could take another look at this thread.
 
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Chalnoth

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I've been looking for that picture, thank you Ryal. And I bumped this looking for possible refutations.
I don't think that refutation is possible. Consider that the evidence of ERV's for common ancestry merely relies upon them being found in the same location in some species, and the same location without the virus in others.

If we merely consider the Lebedev et. al. 2000 paper (which is discussed at talkorigins.org here), we see 14 ERV's that are shown in the figure that are consistent with the phylogenic tree, and not one that was inconsistent.

Imagine, just for a moment, that there is no common descent, that all of these are merely coincidental germline infections. Now, we're only going to look at ERV's that are found in the human genome, and as such consistency with the phylogenic tree requires that each ERV only fits one of the following possibilities:
1. Human-only.
2. Human and chimp only.
3. Human, chimp, and gorilla only.
4. Human, chimp, gorilla, and orangutan only.
5. Human, chimp, gorilla, orangutan, and old world monkey only.
6. All 6 species.

So if there is to be consistency with the phylogenic tree, each ERV must only be among the above possibilities. However, if we are to assume that these are merely coincidences, then there should be no correlation with the phylogenic tree, and thus all possible commonalities are equally likely. So, let's get to counting how many possible coincidental configurations there are:

Just one ERV: Human only (one possibility, as above)
Two ERV's: 5 possibilities (one for each non-human species)
Three ERV's: 10 possibilities
Four ERV's: 10 possibilities
Five ERV's: 5 possibilities
Six ERV's: 1 possibility
Total: 32 possible configurations.

Thus the probability that any one ERV will be consistent with the phylogenic tree is 6/32. The probability that all 14 ERV's are consistent with the phylogenic tree as inferred by other means would be (6/32)^14 = 6.6*10^-11 (that's 0.0000000066%).

There is thus no possible way that these are merely coincidental germline infections. And you may notice that nowhere in this argument did I even bother to worry about how likely such coincidental germline infections would be.
 
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