NewCreature wrote:I'm not overstating insertion point affinity, I am simply pointing out that what was once thought to be random is being shown more and more to be a guided process. There are site specific tranposases, recombinases, and integrases. These factors are at work during the propagation of a viral infection throughout the host cell. When the virus retrotransposes in numerous places throughout the host gamete it has been suggested that this is a viral mechanisms that is “searching” for specific integration sites.
This is a good description.
NewCreature wrote:IT seems that the most likely explanation would be to theorize that infection occurred during a pandemic when many individuals capable of hosting the virus were infected. Again with a directed process of integration we would expect to find patterns. We would not expect to find infections in species that cannot host the virus. Your argument is: “well it is not a random distribution so multiple infections don't work”, but it is being shown more and more everyday that it is a guided process and this determines we will find patterns.
But the problem here is that the insertion is found in every individual of a species with nearly identical sequences. Not withstanding the identical insertion points between species.
NewCreature wrote:BGoodForGoodSake wrote: Insertion points may match up but genetic sequences are highly unlikely to match up as closely as we observe. Nor should we expect to find that the differences would fall into a pattern.
Why?
Here is the reasoning why.
Human genetic material contains ERV's.
There is a set of ERV's shared by all Human Beings.
Your assumption is that some of these were part of the human genome from the beginning by design, and others were aquired via retroviral vectors.
How do we differentiate those which were not there from the beginning and those which are? And shouldn't all have been there from the start because they are found in all human beings?
The same can be said for Chimpanzees and Gorillas.
Yet don't these elements consist of genes which encode for retroviral proteins?
Why discard the possibility that ERV's must be the result of viral insertion.
Can we truly dismiss this by saying that there must be some purpose beneficial to the host, simply because we want to assume design? Can you dismiss a possibility in this manor? Or should we at least entertain the posibility that these are the result of viral infections, based on observations of retroviral action which leads to identical results in somatic cells?
We must admit that somatic injection of retroviral material leads to similar results, and in some cases ERV's still produce retroviral particles, as you have linked to in the previous post.
So now let us switch our views and submit that these shared ERV's are the result of disparate viral injection events. There are several ERV's shared between the three species. In each case the sequences are close. So close in fact that if the only explanation left besides common descent is an intraspecies pandemic.
But lets note the observed patterns. Chimpanzee insertions are more similar in sequence to Humans than that of Gorilla insertions, in every case. How can this be if the insertions occurred during an intra species pandemic?
Would it not sometimes be the case where Gorillas and Chimpanzee sequences are more similar than Humans, or Humans and Gorillas more similar than that of Chimpanzees? Out of three possibilities all cases fall into the observed case, how can this be?
Remember we are talking about a single intra-species pandemic.
To repeat myself I understand how similar species would be subjected to infections from a single virus or a family of viruses, but we should expect an even distribution of sequence variance, not the patterned one we observe.
And finally how did this insertion make it's way into every modern Human, Gorilla, and Chimpanzee? And maintain their sequence similarities.
Remember retroviral genetic sequences tend to mutate at high rates. Yet the insertions found in every individual within a species, is nearly identical.
And similar across species.
Now you have been using three options that are distinct and come with their own problems.
posibility A: ERV's are not the result of retroviral insertions but are designed into the genome.
posibility B: ERV's are the result of multiple disparate insertion events.
posibility C: ERV's are the result of targeted ERV insertions so identical insertion point are bound to happen.
You cannot combine elements from the three possibilities to combat the questions posed in previous threads. As they are not the same solutions.
For instance when faced with identical insertion points, posibility B was given as a solution, that given enough insertions some are bound to match up.
However when data shows that the sequences are similar, you use posibility C to point out that the material is injected in a targeted fashion.
And when the fact that sequence variance shows a pattern posibility A is brought up.
These three solutions cannot all coexist unless there is something fundamental I have missed in your posts.
One of these solutions you are proposing should be able to fit the observations.
NewCreature wrote:BGoodForGoodSake wrote: NewCreature wrote:Scientists have been able to re-synthesize HERV-K and found that it will reintegrate with the same sequence that now appears in the human genome.
Please cite this article, and please let me know if they stated that this resynthesized viral material will integrate at this site exclusively or at least has a statistically high chance of integrating at this site.
I don't think the delibertley infected anyone to take advantage of seeing all the viral mechanisms at work. Here is an abstract, I can't find the exact article I was reading.
There's no need to infect individuals, they can cause the viral particles to infect tissue samples in a culture.
NewCreature wrote:http://www.genome.org/cgi/content/abstract/16/12/1548
from the abstract wrote:This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny.
Same virus; same sequence
But no mention of same insertion point. What this shows is that HERV-K is very likely the result of a viral insertion.
Here you are describing posibility B, that eventually given enough time disparate events among the various species will lead to cases where material is injected in identical insertion points. However in this experiment the viral particles were reconstructed from the ERV itself.
The reconstruction was validated as an acurate reconstruction when it was allowed to reintegrate into the genome and left an identical signature.
However in the wild this viral particle is free to collect mutations during replication, the signature will change with each generation of viral particles.
The infections caused in disparate events will also have dissimilar signatures.
The distribution of cross species analysis should display balanced distribution.
Meaning given three species A, B and C that in some cases insertion sequence is more similar between species A and B than C, more similar between B and C than A, and in other cases more similar between A and C rather than B.
However the data shows that the sequences between species A and B is always more similar than that of species C.
NewCreature wrote:BGoodForGoodSake wrote:
Where does this figure come from?
Try it for yourself.
So here you are again pointing to posibility B. That the vast majority of ERV's are not shared it is bound to happen that some will be similar. Again this would explain the similarities in insertion points but not the similarity in sequence.
NewCreature wrote:BGoodForGoodSake wrote: Having said that you will find that the one's that are shared between the various species fall into a discernable pattern. There are no shared ERV's between Humans and Gorillas which are not shared by Chimps as well.
So What's your point? IF a virus is capable of infecting a human and a dissimilar species like a gorilla it will be very likely of infecting the more similar chimp. Yes the discernable pattern is a result of the guided process; it is not random and we expect a pattern.
Explain how this would occur.
Given the mutational rates of viruses.
(The sequence of retroviral RNA is always mutating)
Why would it never occur that a given sequence is more similar between Gorillas and Humans than Chimpanzees and Humans? Does the virus always infect the Gorilla last?
NewCreature wrote:BGoodForGoodSake wrote: While on the other hand you do find instances of non shared(homologous) ERV's which are shared between Chimpanzees and Gorillas but not in Humans. In this case due to the differences in the sequence and insertion site we are able to determine that these were the result of separate insertion events. .
How are you able to determine that? I am not saying that it is not so, but how can you show that the same event didn't retrotranspose with a unique sequence and into specific locations within the genome of those two whereas mechanisms differ slightly in the human. Also perhaps the human was infected but that virus never made it into a gamete that became an individual. I think you are right that it was an infection by a virus that isn't capable of infecting the human genome. But to just state it as fact without taking into account the site specific tranposases, integrases, and recombinases within the genome of the chimp and gorilla and how those differ from the human, why you are just hypothesizing.
This can be determined because the integration sites of this insertion are not the same. And the sequence differences are far greater pointing to disparate insertion events. In other words the data aligns well with disparate insertion events given our current knowledge of retroviral activity.
The virus must have infected one species and then the other and mutated within their host populations in isolation. And when the viral material finally made it's way into each species genome, the differences in sequence align well with expected mutation rates of retroviruses.
Exactly what would be predicted by option B from above.
NewCreature wrote:BGoodForGoodSake wrote: If it were the case that ERV's which are shared is due to separate infection events and fall into a pattern because similar species are more likely to be infected by the same viral vector than how can the above be explained?
WE could offer several potential explanations. Here are two. Separate events where in one virus the gorilla was immune and in the other the human was immune. Same event but unique integrases, recombinants, etc resulted in disparate viral signatures. Perhaps if you would like to take the time we can come up with several other possibilities. You seem rather to hold to a position rather than to really engage and inquire.
Let us consider these posibilities.
In these posibilities you hold that one of the species is immune. Thus resulting in the PTERV case. This is fine.
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But that does not explain why there are no shared insertion points between the remaining two species.
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And this does not explain why the insertions in the remaining species have such sequence variances.
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Nor does this explain why in cases where the three species do share an insertion point the sequences vary by much less than expected by independant insertion events.
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And neither does this explain why in cases where the three species do share an insertion point the patterns are always the same.
Also lets refer back to the ERV-K Phoenix viral particle. The phoenix insertion exhibited the exact same signatures in hamster, cat and human cells. This would seem to be counter to your assertion that the same viral class would exhibit different insertional signatures because of the uniqueness of each species genome.
NewCreature wrote:BGoodForGoodSake wrote: What is the probability that such random insertions from multiple insertion events fall into such a pattern?
What is the probability that an apple is an orange? It is not a random process. The virus has an affinity for similar locations, and mechanisms exist to guide the process as the virus retrotransposes throughout the host cell.
That is solution C, but my statement was in responce to the following statement.
"With about 30,000 different ERV infections in both chimps and humans it is highly likely that the most favorable site for a particular virus will become infected. If you take the number of shared ERVs and divide them by the total number of ERV infections in the genome you will find that 99% of them are not shared."
In this case you are saying that there are many likely insertion points, ie possibility B. And that the sheer number of insertions will lead to shared insertion points. You are saying that the matching insertions are a chance occurrence given the large number of unshared insertions. So again I will ask, what are the chances of random insertion events leading to similar sequences in these identical insertion points?
And if we are not putting any significance in the number of infections what is the significance of the 99% figure? This was the figure that this portion of the conversation stems from.
NewCreature wrote:BGoodForGoodSake wrote: NewCreature wrote:While retroviruses do have an affinity to integrate at certain locations, not all integrations will result in a viral outbreak. It would seem that the viruses have the ability to integrate at different locations in a guided manner so that results in them being inserted in specific location eventually.
You seem to be addressing insertion points only without focuising on the sequences of these insertions.
Yes that is right. One thing at a time (sort of). Please see the reconstructed retrovirus “phoenix”.
Phoenix addresses sequence, the sequence of a reconstructed virus which has not had the chance to mutate freely in the wild. Therefore sequence was a result of the transcription process only. No mutations were involved and thus this could not characterize disparate insertion events. Additionally in the paper you linked to there were no shared insertion points.
"Finally, we mapped the three Phoenix insertion sites using the UCSC Genome Browser and found that integration occurred within (for two of three) or close to (<20>100 kb on each side), four being in the vicinity (<20 kb) of genes, and only two inserted within genes (M. Dewannieux, unpubl.)."(1).
As you can see here insertion preference is for transcribed regions. And in the relatively small sample none of the insertions occurred in identical locations. So in this case you addressed sequence, however in a misguided way, and did not address insertion location. Remember the key is location AND sequence.
NewCreature wrote:To try and sum up I will make some comments in response without further quotes. IT is quite likely that sequences wouldn't be the same for different viruses. Each virus will integrate in a unique way. This is why the patterns do not match for separately integrated material. Further a review of genomes will show you that most of the time viruses appear to be separate and isolated incidences. This is why a pandemic is the likely cause of the same sequences in the same location.
Sequences are not the same for different viruses by definition. Each class of virus integrates in a unique way, not each individual virus of the same class. In other words all deltaretroviruses for example insert their genetic material in more or less the exact same manor.
Slight variations can arise due to mutations in the ENV encoding protein.
Revisiting the pandemic possibility, you say that this explains similar sequence in the similar location, but have yet to address the distribution of similarities. Why are Chimpanzee sequences always more similar to Human than Gorrillas are to Humans if the infection is the result of a single pandemic episode?
NewCreature wrote:You say you can handily disprove this.
I did?
NewCreature wrote:Perhaps we will just have the jury disregard that statement if you intend to leave it empty. Same virus leads to same sequence. Same mechanisms with numerous sites leads to a high probability of a pattern developing resulting in instances of shared sites.
Yes but what pattern would we expect? I will repeat again
should we not expect an even distribution in which in a third of the cases the Human and Chimpanzee sequences are the most similar, and in another third the Human and Gorilla sequences are the most similar and finally in the last third the Chimpanzee and Gorilla sequence is the most similar? Also this is ignoring all of the other species which also share the same insertion points and have the same pattern of sequence discrepancies.
NewCreature wrote:This guided process is not statistically random, although I know that from the early days it has been the prediction of evolutionists that it would be found to be so.
Site this please, as far as I am aware insertion point affinity is not a new concept.
Don't confuse affinity with limited possibilities. Affinity still leaves multiple possible insertion points, where among the preferred sites the viral material will insert is statistically random.
NewCreature wrote:We find that individuals and species do in fact share sequences and share insertion points. Viruses have an affinity for an insertion point and there are site specific recombinases, integrases, etc. This is a guided process and insures that specific locations will eventually be found by the viral outbreak.
Again you are pointing to possibility B. It seems that the majority of your points refer to this posibility.
Namely that ERV's are the result of multiple disparate insertion events.
Let's then focus in on this hypothesis.
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How then does the insertion get propagated to every individual in the species?
Isn't it true that as time goes on that viral material will change at a much faster clip than the genetic material found in mammals? Proof for this can be found in the fact that HERV's within Humans are close to identical in all members.
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If the above is true than how much time has to elapse in order for the species involved to be infected? Keep in mind that HERV-K homologs are found in New World Monkeys, Old World Monkeys, Great Apes and Humans all in the exact same insertion point.
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How likely is it that each species fix the same insertion within the same time period within each respective genepool?
Why the same timeperiod? because as time goes on the genetic code of the virus become less and less like that of the original virus.
1. Dewannieux, M, Harper, F, Richaud, A, Letzelter, C, Ribet, D, Pierron, G & Heidmann, T. (2006) Genome Res 16, 1548—1556.