Lines of Evidence ( Part 1 : ERVs )

lewiscalledhimmaster

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Though my initial thread was obviously too vast in scope, I have decided to work through each if it's primary topics as thoroughly as possible.

As threads have a tendency to wander off-topic, I hope we can engage the following posts from the initial thread: LINES OF EVIDENCE :

<edit>

Let's go with ERV for the moment, eh? In simple words: a virus reproduces by inserting his genes into cells, so that they make new viruses.

Sometimes, those pieces of Virus DNA are inserted into a DNA that is used for reproduction. Henceforth, this Virus DNA piece is part of the "normal DNA" and might stay there for a very long time.

So, if we see a piece of ERV DNA in human genes, and we see the same piece of ERV DNA in the genes of other apes, we can tell that we once had a common ancestor. We do see that, so this is an argument for evolution.

I'ld like to add to that, that we can do such a thing for just about any "genetic marker". What you'll find is that the closer related the species, the more "genetic markers" they have in common. ERV's are just one such example.

<edit>
 

lewiscalledhimmaster

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I know it's hard to wake up our mental faculties, especially when it comes to heavy peer-reviewed papers. Well, maybe you do this for a living, teacher, researcher etc. In that case, I am looking forward to your input.

I was hoping my OP might kick start the topic of how ERVs fall into the category: LINES of Evidence which relate to Evolution -- but it's obviously not enough, so I guess asking elementary questions might work better. (ie. In layman's terms what are ERVs? How do ERVs help us in our pursuit of evidence which relates to Evolution? etc.)

There are a couple of good sites* for solid papers, but knowing very little about this -- I am throwing this one in for y'all peace: Human endogenous retroviruses in health and disease: a symbiotic perspective by Frank P Ryan, FRCP FLS


~~~
*http://m.genome.cshlp.org/ / http://genomebiology.com/
 
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lewiscalledhimmaster

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It's just you and I, Readers, Lurkers, Trolls and Newbies.

I decided to give the linked paper, in post 2 a go, and this stood out as a great introduction to ERVs:

'....Retroviruses were originally discovered when Peyton Rous noticed the effects of the avian sarcoma virus in 1910, but their infectious and pathogenic potential for humans only became clear with the discoveries of the sexually transmitted human T-cell leukaemia viruses, HTLV-I and HTLV-II, and even more so with the arrival of the human immunodeficiency viruses, notably HIV-1, which ushered in the lethal pandemic now underway. ....'*

~~~
* Human endogenous retroviruses in health and disease: a symbiotic perspective
 
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lewiscalledhimmaster

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A little more for y'all:

'.... Exogenous retroviruses, like HIV, reproduce within the somatic tissues of infected individuals and spread in the human population through sexual intercourse and contaminated blood products as well as from mother to child by passage of virus transplacentally or during parturition, or via breast milk. Although it is likely that the HTLV and HIV viruses first infected humans through cross-species spread from animal hosts, their natural host is now the human species. Endogenous retroviruses (ERVs) have invaded the germ cell lines of every species of vertebrate. Here they replicate in Mendelian fashion, as an integral part of the sexual reproduction of the host, to inhabit the genome of all future generations. This is known as germline transmission. It has important evolutionary, physiological and pathological implications. ....'*

~~~
* Human endogenous retroviruses in health and disease: a symbiotic perspective
 
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lewiscalledhimmaster

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Loudmouth

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I was hoping my OP might kick start the topic of how ERVs fall into the category: LINES of Evidence which relate to Evolution -- but it's obviously not enough, so I guess asking elementary questions might work better. (ie. In layman's terms what are ERVs? How do ERVs help us in our pursuit of evidence which relates to Evolution? etc.)

First, our genomes are pretty big at 3 billion bases, so retroviruses have a lot of places to insert. While a specific retrovirus may prefer a type of area to insert into, there is no specific preference that would cause 99% of insertions to occur at the same position.

With respect to the randomness of insertion, this is a good paper to look at:

Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences

In that paper, they allow three different retroviruses to insert into genomes and then map where they insert. Fig 1 is a map of those insertions, with each of the retroviruses in different colors and all human chromosomes.

pbio.0020234.g001.jpg


As you can see, they insert all over the place. They did find that HIV has a strong preference for transcriptional units, but those units cover about 1.5 billion bases of the 3 billion base human genome:

"For HIV the frequency of integration in transcription units ranged from 75% to 80%, while the frequency for MLV was 61% and for ASLV was 57%. For comparison, about 45% of the human genome is composed of transcription units (using the Acembly gene definition)."

We know from direct observation that two insertions happening in two separate species will only rarely produce identical insertions at the comparable base in each genome. Therefore, if we see that >99% of 200,000 ERV's in the human and chimp genomes are found at the same base, this is smoking gun evidence of common ancestry. We get the 200,000 figure from human and chimp genome papers, if you are interested.
 
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Loudmouth

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Just for reference, the first table is from the human genome paper and it has the number of ERV's in the human genome which gives a figure of about 200,000.

409860at-011.gif

Table 11 : Initial sequencing and analysis of the human genome : Nature

The second table is from the chimp genome paper, and it lists the lineage specific ERV insertions in each genome. How did they determine which ERV's are lineage specific? Those are the insertions that are not found in the other species. Therefore, humans have 82 ERV's that are not found at the same position in chimps, and chimps have 279 ERV's that are not found at the same location in the human genome. By subtraction, this means that more than 99% of the ERV's in each lineage can be found in the other lineage.

nature04072-t2.jpg

Table 2 : Initial sequence of the chimpanzee genome and comparison with the human genome : Nature

Creationists will try to claim that only a few have ever been found to be at orthologous positions. Don't be fooled.

Also, creationists will try to claim that finding the same retrovirus in two distantly related species is a problem. Don't fall for it. What they fail to mention is that the actual insertions are found at non-orthologous positions, just as it should be if evolution is true. The evidence for common ancestry is the shared position in the genome. Don't forget that.
 
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lewiscalledhimmaster

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Don't forget that.

I didn't want to post here, but I'm using an android which for some reason does not like popup windows -- So, I cannot give you kudos.
This is what I would have said: Thank you so much for making this thread worthwhile. You rock!. :thumbsup:
 
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Loudmouth

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Thought I would cover a few of the more common creationist attempts to refute the ERV argument. Creationists often reference this webpage written by the Discovery Institute:

Do Shared ERVs Support Common Ancestry? - Evolution News & Views

There are quite a few failed arguments on that webpage, so I will try to focus on one point per post.

The author, Johnathan M (JM hereafter), tries to argue that retroviral preferences for insertion can produce the number of shared ERV's seen between humans and chimps. Like many other creationists, he cites this section from a peer reviewed paper:

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.
http://www.ncbi.nlm.nih.gov/pubmed/9645463

This is actually a review paper, so lets go to the original paper to get a better handle on the probabilities involved, found here:

http://genesdev.cshlp.org/content/8/12/1473.full.pdf+html

The first thing we need to establish is the probability that we are multiplying by 280. The authors of the paper describe that probability here:

A pool of 10 ug of infected TEF DNA (from 5x 10^6 cells) would therefore contain 1-1.5 x 10^7 integration events. If integration occurred at random throughout the genome (size 2x 10^9 bp) we would expect to see about two to three integrations, in each orientation, within the 500-bp stretch of DNA analyzed in each reaction.​

Just to show that we have the right paper, here is the claim of a 280 fold increase in insertions:

Again, we observed a localized preference for some sites over others (arrows), with one site used 280-fold more frequently than random.​

So let's do the math. A retrovirus that was truly random would insert 2 or 3 times into a 500 base pair stretch of DNA, and that is out of 1 x 10^7 total insertions (which is 10 million insertions). Therefore, a 280 fold increase would be about 750 insertions into this 500 bp stretch and 9,999,250 insertions elsewhere in the genome. This means that the chances of two independent insertions occuring at this specific motif is just 1 in 13,000 or so. Not that great of odds.

If we were to assume a worst case scenario where every insertion is at a base in the genome that has a 280 fold better probability, how many insertions would we expect to be shared by humans and chimps? Out of 200,000 we would expect about 15 to be shared between humans and chimps, if independent insertions are truly the source of the orthologous insertions. Less than 1% of ERV's should be orthologous if they are due to independent insertions.

This may explain the big lie that JM then tells. Here it is:

Out of tens of thousands of ERV elements in the human genome, roughly how many are known to occupy the same sites in humans and chimpanzees? According to this Talk-Origins article, at least seven. Let's call it less than a dozen. Given the sheer number of these retroviruses in our genome (literally tens of thousands), and accounting for the evidence of integration preferences and site biases which I have documented above, what are the odds of finding a handful of ERV elements which have independently inserted themselves into the same locus?​

If you read my previous posts, you will spot the error with ease. There is really no excuse for making the claim that there are only about a dozen ERV's shared by humans and chimps. JM wrote that article in 2011, 6 years after the chimp genome paper was published, and 10 years after the human genome paper was published. The number of ERV's in the human genome is about 200,000. The number of shared ERV's between humans and chimps is more than 99% of those ERV's, not a dozen or so. The argument that JM uses should produce fewer than 200 shared ERV's. We see over 200,000 shared ERV's.

The creationist argument is bunk.
 
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Loudmouth

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The second topic I would like to discuss from the Discovery Institute article by Jonathan M (JM hereafter) is Pterv insertions. As I will show, this argument actually blows up in the face of creationists. Remember what I said in a previous post about creationists trying to confuse the reader where it concerns species distribution and orthology? This is one of the best examples that one can find. Even more, it ends up supporting evolution in a way that completely contradicts the creationist argument.

The peer reviewed paper under discussion is this one:

Lineage-Specific Expansions of Retroviral Insertions within the Genomes of African Great Apes but Not Humans and Orangutans

The Discovery Institute webpage can be found here:

Do Shared ERVs Support Common Ancestry? - Evolution News & Views

It discusses the discovery of Pterv insertions which are found in the chimp and gorilla genomes, but curiously not in the human or orangutan genome. Pterv insertions are also found in other primate genomes. The theory of evolution would predict that with this species distribution, these insertions had to occur after the chimp and human lineages split. If they had occured in the common ancestor of chimps and gorillas, then humans should also have these insertions because humans share that same common ancestor. Humans don't have those insertions.

Since evolution predicts that these were independent insertions, it would also predict that given the number of insertions (about 300), we shouldn't find any or very, very few orthologous insertions.

This is where JM uses selective quotes to give the impression that there are 12 orthologous insertions shared by chimps and gorillas. It is in the grey quote box towards the bottom of the page that starts, "We performed two analyses to determine whether these 12 shared map intervals might indeed be orthologous. . ."

Strangely, or predictably, JM does not discuss the analyses that they used to determine if those 12 candidates are truly orthologous. A bit of background . . .

So why are there 12 candidates to begin with? From the real scientific paper:

WARNING, HEAVY SCIENCE CONTENT TO FOLLOW, SKIP TO LOWER SECTION IF YOU WISH .. .

A total of 275 of the insertion sites mapped unambiguously to non-orthologous locations (Table 2), indicating that the vast majority of elements were lineage-specific (i.e., they emerged after the divergence of gorilla/chimpanzee and macaque/baboon from their common ancestor).

Within the limits of this BAC-based end-sequencing mapping approach, 24 sites mapped to similar regions of the human reference genome (approximately 160 kb) and could not be definitively resolved as orthologous or non-orthologous (Table S3). We classified these as “ambiguous” overlap loci (Figure 3). If all 24 locations corresponded to insertions that were orthologous for each pair, this would correspond to a maximum of 12 orthologous loci. [emphasis mine]​

So what do they mean by a "BAC-based end-sequencing mapping approach". You first need to understand what a BAC clone is. A BAC clone is an E. coli clone that carries a plasmid with a big chunk of genomic DNA from the species being studied. They break the chimp, gorilla, or other genome down into chunks anywhere from 10,000 to 500,000 base pairs, and put them in a plasmid so that E. coli can store and replicate that DNA. When you sequence DNA, you need to start from known DNA. Since you know the DNA sequence of the plasmid, you can start your sequencing there and sequence into the big chunk of DNA. Most sequencing reads are about 1,000 base pairs, so you can get the sequence for the 1,000 base pairs at either end of the big chunk of genomic DNA. This allows you to know where that chunk belongs in the larger genome.

However, you only know the 1,000 base pairs at each end. This means that the ERV insertions detected in these BAC clones could be anywhere within that big chunk of DNA. All they know is that it is in there somewhere, but they don't know which base it is at. This is what they mean by "Within the limits of this BAC-based end-sequencing mapping approach". They only have the ends, and not the middle where the insertion is.

END OF HEAVY SCIENCE CONTENT, IF YOU SKIPPED THE MATERIAL, START HERE . . .
So as we can see, the BAC based method can not show us if these 12 candidates are truly orthologous. They can't show that the insertions are at the same base, only that they are within 10,000 or 100,000 bases of each other. What JM does not want you to know is that they used other methods to determine if these insertions were truly orthologous. Here is the rather large quote that you can skip and read my summary below:

For the three intervals putatively shared between macaque and chimpanzee, we attempted to refine the precise position of the insertions by taking advantage of the available whole-genome shotgun sequences for these two genomes. For each of the three loci, we mapped the precise insertion site in the chimpanzee and then examined the corresponding site in macaque (National Center for Biotechnology Information). In one case, we were unable to refine the map interval owing to the presence of repetitive rich sequences within the interval. In two cases, we were able to refine the map location to single basepair resolution (Figures S4 and S5). Based on this analysis, we determined that the sites were not orthologous between chimpanzee and macaque. It is interesting to note that this level of refined mapping in chimpanzee revealed 4- to 5-bp AT-rich target site duplications in both cases. These findings are consistent with an exogenous retrovirus source since proviral integrations typically target AT-rich DNA ranging from 4 to 6 bp in length [24]. Although the status of the remaining overlapping sites is unknown, these data resolve four additional sites as independent insertion events and suggest that the remainder may similarly be non-orthologous.​

Summary: IOW, for the insertions that they could confirm down to the base pair, they weren't orthologous, and they suspect the same will be true of the others. To claim that there are 12 orthologous Pterv insertions shared by chimps and gorillas based on BAC clones is a massive leap of faith.

But here is a more interesting aspect of this data, IMHO. ID/creationists will argue that it makes sense that ERV's are found in the same spot in the chimp and human genome because a common creator would use common building blocks. Since chimps and gorillas supposedly share a common creator, shouldn't we see the Pterv insertions shared in the same way that other ERV's are shared between humans and apes? I don't see why not.

What we have here is a set of DIFFERENT predictions made by the common creator group and the evolution group. The comon creator group makes the argument that Pterv insertions should be orthologous, just like the hundreds of thousands of ERV's that are orthologous between the chimp and human genome.

Evolutionists make the exact opposite argument based on the phylogeny of humans and apes. Evolutionists predict that they should NOT be orthologous because they would have to have been independent insertions that occurred after the human and chimp lineages split. This is based on a phylogeny, something that the common creator argument does not have.

So how do those predictions fare? The common creator argument is completely refuted, and the evolutionary prediction turns out to be completely right. Go figure.
 
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AV1611VET

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It is one of those science things that involves evidence ...

Which is severely lacking.

Macroevolution is a game of connect-the-dots.

It has vastly more missing parts than parts.
 
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Loudmouth

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Which is severely lacking.

It is found in the posts you are not responding to.

Macroevolution is a game of connect-the-dots.

It has vastly more missing parts than parts.

The parts aren't missing. I discuss the parts in the posts you are not responding to.
 
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OldWiseGuy

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The average person has to accept evolution on faith, as they will never understand the science behind it. How do scientists feel about having to 'sell' the theory knowing that the 'proof' is unintelligible to the average person.

Just today I learned the fully half of the genes of common yeast are interchangeable with human genes. My response was, why not? God made everything basically out of the same stuff.
 
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crjmurray

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The average person has to accept evolution on faith, as they will never understand the science behind it. How do scientists feel about having to 'sell' the theory knowing that the 'proof' is unintelligible to the average person.

The average person has the ability to access the majority of human knowledge by going to their local library. They have access to the information that backs all current scientific understanding. Just because you don't understand it, doesn't mean you can say the majority of people can't.
 
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OldWiseGuy

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The average person has the ability to access the majority of human knowledge by going to their local library. They have access to the information that backs all current scientific understanding. Just because you don't understand it, doesn't mean you can say the majority of people can't.



Understanding evolution isn't a high priority for most people.
 
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crjmurray

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Understanding evolution isn't a high priority for most people.

Neither is understanding physics. Hell, I just started a thread that shows that a few users here don't understand basic math. Does that mean we take math on faith?
 
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