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Replying to post 491 by theStudent]
I will be using
this site for the majority of referenced information.
The life cycle of an ERV is this:
1. Injection of the RNA-based viral genome into the host cell.
2. Replacement of existing host genome sequence with the injected genome (the RNA is transcribed into DNA by the way).
3. The host cell then uses the molecular machinery it is composed of to unwittingly reproduce the viral genome.
4. The reproduced viral genome is sent away from the host cell, destroying the host cell in the process.
This is the normal scenario.
In order to replicate itself, a retrovirus needs to use the molecular machinery of a host, and it begins the process by first binding its extracellular and transmembrane glycoproteins to a cells coreceptors. The capsid"containing the retroviral enzymes reverse transcriptase, integrase, and protease, as well as two copies of the retroviral genome"is inserted into the cells cytoplasm, where it uncoats. Now in its host cell, a retrovirus reverse-transcribes its genome from RNA to DNA via reverse transcriptase. Protease then process the viral DNA by removing a dinucleotide off each 3 end, and integrase inserts it in the host cells genome (Targeting HIV replication, n.d.). Once integrated, and in DNA form, its genome is known as a prototype retrovirus, or provirus. Upon integration, the cell is allowed to divide, and eventually the presence of certain environmental conditions trigger proviral activation. Copy after copy of the retrovirus is produced as virions bud off, mature, and go on to infect other cells, leading to the death of the infected cell.
https://www.youtube.com/watch?v=9aDNwlRaJqw
However, I must make a concession, and one that is intensely crucial toward the rest of this discussion.
Retroviruses circumvent the problem of vanishing promoters by simply polymerizing copies of them during reverse transcription. They achieve this by possessing identical sections of DNA, called repeats, on either terminus of their genome. Early in the process of reverse transcription, the first jump occurs, in which the transfer RNA (tRNA) primer detaches and the DNA repeat hybridizes with the remaining RNA repeat at the genomes 3 terminus (Cann, n.d.). Given the relatively small size of the repeats, if they are not identical, they cannot hybridize. As for the 5 unique (U5) and 3 unique (U3) sections, a copy of each is polymerized on the opposite terminus. Between the necessity of identical repeats, and the duplication of unique sections, the resulting U3-R-U5 sections, called long terminal repeats (LTRs), must likewise be identical at the time of insertion. This will become very important later on in examining the second and third layers of ERV evidence.
In this regard, retroviral insertion into the host genome is
mostly random, but relies on certain conditions to be met that isolates the insertion site.
However, these conditions are minor.
Different retroviral integrases have minor statistical biases for insertion within the general area of chromosomal regions rich in expressed genes [their interwoven] CpG islands active genes [and areas] near transcription start sites (Mitchell et al., 2004), but these biases are so minor, that they require thousands of trials (3127 used in the Mitchell study) just to detect them. For the most part, the process of integration is observed to be quite random.
Additionally, we know that these retroviruses were likely not always there, since we can see evidence of pre-integrated DNA sequences. Remember, under evolutionary theory, this is explained in simple terms: Species with similar DNA sequences who lack the provirus would be evidence for what the host's pre-integrated genome would look like (in certain areas).
The second effect of the insertion is the displacement of DNA. This can be observed by comparing corresponding genomic areas in species with and without the provirus. The ones with the provirus display a target site duplication, where as the ones without the provirus display the preintegration site (Polavarapu, Bowen, & McDonald, 2006). The presence of these two effects conclusively demonstrates that the sequence in question was inserted into the host's genome via a transposase enzyme at some point in history of the host's lineage.
Usually targeting somatic cells, a retrovirus will occasionally target a sperm/egg cell, causing quite a change to the life cycle.
The targets of retroviruses are usually somatic cells, but if the infected cell happens to be a sperm or egg cell, known as a gamete, or a testicular or ovarian cell that divides into a gamete, that gamete may be used to produce an offspring. In such a case, the provirus becomes a permanent fixture within the offsprings genome. Its permanence is due to fact that there is no mechanism for removing proviruses precisely from the genome, without leaving behind a solo LTR or deleting chromosomal DNA (Johnson and Coffin, 1999). Although the retrovirus was foreign to the organism it infected, and thus would be considered exogenous to that organism, once passed on to the organisms offspring, it would be present in the offsprings natural, healthy state, and thus would considered endogenous to it.
In this situation, the normal scenario changes in the following way:
3a. The host cell will contain retroviral DNA in its genome, and these chromosomal insertions are capable of being passed down in the same way endogenous DNA is, through the chromosomal swapping that gives the new offspring its DNA blueprint.
3b. With no method of removing the ERV, it becomes a natural component of the genome.
3c. The ability of retroviral DNA to remain dormant for periods of time, it can be made inoperable in terms of its original function; that is, it will cease to reproduce itself.
Most proviruses have the ability to go dormant for long periods of time, only activating themselves when environmental conditions are right. In the meantime, the silent DNA of these viruses is being replicated every time the original host cell and the host cells offspring divide.
One of the most famous retroviruses is known as human immunodeficiency virus, or HIV.
Fascinatingly, there are many retroviruses that stay dormant for so long that they become permanently incorporated into the host genome. If these retroviruses happen to target the germ line- i.e., the cells that will eventually form gametes- they are passed on to the hosts offspring. These are called endogenous retroviruses. It is estimated that at around 8% of the human genome is actually incorporated endogenous retroviral DNA.
Source:
https://koryoswrites.wordpress.com/genetics/
Since ERVs are generally not conserved, they accumulate mutations at the same rate as introns. And, as with introns, over time, the mutations can become fixed in the host populations gene pool (Boeke and Stoye, 1997. In Coffin, Hughes, & Varmus, 1997). Given enough time, enough mutations accumulate to render the ERV incapable of activation.
Understanding all of these factors, we are ready to begin.
The ERV's are evidence for common ancestry in the following way:
Evolutionary theory provides the explanatory power to determine why the vast majority of ERV's in humans and chimpanzees align in orthologous matches. The only way this could be possible without utilizing the evolutionary theory would be if the ERV's were randomly injected into the ancestors of chimpanzees and humans separately, at the exact same location.
Not only are there many ERVs shared among primates, but they are shared in hierarchical subsets of the whole. Each set falls within another set, giving an unbroken line of inheritance for every species (Kurdyukov et al., 2001; Lebedev et al., 2000). This pattern is called a nested hierarchy. These patterns further corroborate that the many species of primates share common ancestry, and necessitate a specific sequence of divergence from one ancestral species to the next. They are wholly inexplicable by the model of uncommon ancestry.
As previously explained, although the LTRs of a provirus must be identical upon insertion, once endogenized, they begin accumulating mutations. Any mutations to one LTR become quite apparent, as they are not accompanied by the same mutations in the other. Thus each mutation causes the ratio of discontinuity between the two LTRs of a full-length ERV to increase. Since ERVs in identical loci among greater numbers species of wider taxonomic separation correlate to older insertions, if the evolutionary model is correct, they should also have higher ratios of discontinuity between their LTRs. And what do we find? We find just that; a pattern, where the degree of a shared ERVs LTR-LTR discontinuity is proportional to the degree of taxonomic separation between the species that share it (Johnson and Coffin, 1999). There is deviation from the pattern"likely caused by viral transfer and interelement recombination/conversion (Hughes & Coffin, 2005) and viral transfer (Belshaw et al., 2004)"but the pattern is holds for many full-length ERVs and is explainable only by decent with modification from a specific series of common ancestral species. Once again, we see strong evidence for ERV orthology.
This excerpt emphasizes that the evolutionary model is capable of making predictions based on our knowledge of ERV's and common ancestry; we are capable of asserting reliably that a greater number of matches will correlate to closer relations within taxonomic boundaries. If evolutionary theory
were not true, this
would likely not have happened.
We've already done examinations of the human and several other genomes. We know how to look for a variety of effects, such as deletion, insertion, and substitution of nucleotides that result in alterations to genes. By comparing human and chimpanzee genomes...
When the genomes of multiple organisms are aligned, an indel [deletion or insertion] in either genome will result in a gap. This is useful in determining the how many ERVs, Alus, or any other types of transposons are shared, since insertions at a given locus in only one lineage or only the other will result in gaps, yet insertions in identical loci leave no gaps:
...
But the total indel variation between the chimpanzee and human genomes is only ~3%, comprising a maximum of ~45 Mb (~1.5%) in each genome (Chimpanzee Sequencing and Analysis Consortium, 2005). Remember; that includes deletions and duplications, as well as the insertion of transposable elements, like ERVs.
ERV Predictions from the Evolutionary Model
As primate genomes continue to be sequenced in full, and compared to the human genome, it will be found that as the degree of taxonomic separation of the compared lineages increase:
1) The ratios of ERVs, Alus, and other transposable elements not in identical loci to those in identical loci will gradually increase"from the current human to chimpanzee ratios of ~0.1% for ERVs and ~0.6% for Alus (IHGS Consortium, 2001; CSA Consortium, 2005).
Explanation: The older the divergence between the compared lineages, the more time each has had as a distinct lineage; thus the more independent insertions each should have accumulated.
2) The solo-LTR to full-length element ratio of the ERVs in identical loci will rapidly increase.
Explanation: Insertions tend to rapidly undergo homologous recombination, but as soon as it begins accumulating mutations, its chance of recombination rapidly decreases (Belshaw et al., 2006). Thus there are very old full-length ERVs, but their numbers fall off quickly with age.
3) Transposable elements in identical loci will largely be arranged in accordance with the current nested hierarchy of examined elements, but between insertion symplesiomorphy caused by incomplete lineage sorting (i.e. allelic segregation), and insertion homoplasy caused by target site preference, the amount of pattern deviation will increase beyond the current solitary case of HERV-K-GC1. The majority of this increase will involve the deviation of only one lineage per deviant identically positioned ERV.
Explanation: A site being used twice is quite rare, and a site being used three times is not observed; even in a sample of 40,528 HIV insertions (Wang et al., 2007). This"in addition to tendency towards allelic fixation"indicates that insertion symplesiomorphy/homoplasy will likely be limited to only one point of deviation at a time; as is the case with HERV-K-GC1 (Barbulescu et al., 2001) and Ya5AH137 (Salem et al., 2003).
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Now that I've gone through the pertinent information, I'm going to take some time to walk through all of the objections you've raised to my posts in this thread in the past, and try to address every single one of them. I will then raise several challenges to you that I request you take into account.
Can scientists prove that ERVs came from retroviruses?
Also, can ERVs be mutations in the genes?
Answer: Scientists have verified that ERV's came from retroviruses due to the nature of ERV's, how they operate, and from the existence of modern day retroviruses.
ERV's are not mutations in the genes. For an ERV to mutate randomly, it would have to be a very smart gamete to know the major reproductive RNA strands that compose retroviruses, how to reverse transcribe it into DNA, and plop it into the genome fresh out of the oven. Unless you'd like to argue that these mutations have accumulated over time to eventually resemble retroviral RNA; the short answer is, this wouldn't work either, unless you're willing to assert that it randomly mutated into the genome for both humans and chimps.
What ancestor is/was the original carrier?
Which decendants would have been affected?
Answer: Depending on the retrovirus and the time of insertion, the ancestor that originally carried the new genome would vary. Some would have lived 30 million years ago, some 18, some less. Even a single organism that passes on this altered genetic structure would leave a lasting impact on all future descendants. This would be an unavoidable effect.
Understand that the timescale for this is unthinkably vast. We're talking about roughly 200,000 ERV's being injected into animals over the course of Earth's history, which is speculated to likely take some 500 million years. Entire millennia are likely to occur without novel gene insertion taking place; the odds of such a situation happening are incredibly slim, but they happen over the course of such long periods of time that these unusual events do occur, and accumulate.
Neatras wrote:
3. Individuals who are closely related to an ancestor will share more ERV's in the appropriate location with each other, than they would with individuals who are more distantly related.
Why would this be the case?
In the event where common ancestry is true, then that implies that humans and chimpanzees share common ancestors. If one of those common ancestors developed an ERV, it would pass down to both chimps and humans.
What if chimps are more distant than other primates?
Would that not prove the theory false.
Short answer: No.
Long answer: We share the majority of ERV's we have with a large number of primates.
Another question I have is based on this item:
According to the American Journal of Tropical Medical Hygiene, the presently leading causes of death among American missionaries in Africa are motor accidents, malignancy, and atherosclerosis. Among infectious diseases, the biggest killer is viral hepatitis, followed by such diseases as malaria, rabies, typhoid, Lassa fever, and retroviral infections.
http://www.scielo.br/scielo.php?script= ... 0030004000...
https://africacheck.org/factsheets/fact ... th-in-afri...
http://www.ajtmh.org/content/73/3/560.full
Given the deadly nature of these viruses, how could it now be found in one location of an organism, if passed on by a carrier ancestor over millions of years?
Shouldn't it have killed off the descendants, if not an ancestor?
I'm glad to have finally found reliable sites capable of explaining how a dormant ERV can be rendered inactive. It's likely that this hasn't happened for every retroviral infection in history; the likeliness of a dormant ERV being mutated into inactivation is very much low. But over broad stretches of time, and with enough samples, even a single ERV being rendered endogenous to its host's genome will have lasting impact.
Why is the viral infection started at that point, and not lower in the tree?
Is it because of the organisms that were affected?
There are 2 valid answers here.
1. Over the course of millions of years, some viruses would evolve or go extinct, resulting in their genome no longer being accessible exogenously.
2. The odds that a retrovirus will infect a gamete, become inactive, and successfully be passed down are absurdly low. And they most certainly will not occur in the same region of the genome if injected exogenously multiple times. Common ancestry is the only theory in existence with the power to explain why ERV's function the way we observe them to in reality.
If over a slow process of evolution, the genes are carrying destructive data, it will either be repaired, or become more destructive.
One leads to healing. One leads to death.
The alternative is that ERV's are just as likely to mutate as any other endogenous genome component, and these mutations can have a variety of effects. If it has ever 'reactivated' due to specific sequences occurring, I'd
love to see that, because it is such a novel event that it would spark discussions worldwide!
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It is now that I am going to discuss your behavior in this thread so far.
Repeatedly, you have shown an ineptitude with regard to how you view science.
Science does not deal in proofs. Requiring every single bit of evidence to "prove" something is illogical. A theory exists to explain the facts, how can those facts then be made "proof" of a theory? The answer is that they don't; they simply lend credibility to the theory if it is capable of explaining the facts reliably, every time. Evolutionary theory has successfully lasted through another wave of facts being presented. When ERV's were discovered, evolutionary theory was left intact; it did not get destroyed, and in fact common ancestry wasn't even revised. It was considered a natural, congruent component for how life would have developed. You have so much concern with theories "changing over time" that I'm wondering how you'll react to a theory you so strongly dislike remaining resolute because of new evidence.
In all of this time, the objections you've raised are that "evolution doesn't explain the origins of life", but we've taken special care to time and again admonish you, and to explain that evolution naturally doesn't make any claims about the origins of life, merely the origins of the diversity of life. If you keep harping on this point, it demonstrates that you're not willing to discuss pertinent topics, and instead want to remain trapped in your bubble, beating down strawmen. If that is what happens, I'm going to have to point out to everyone that your topics, discussions, and debate tactics are neither constructive nor informative, and should be discarded to the wayside.
Please don't let me down. Show that you can learn.
My challenges are as follows:
Please attempt to explain ERV's using whatever explanatory power you believe your ideas carry. Please try and use uncommon ancestry to explain the diversity of both life and ERV's that utilize the evidence available to us.
