Endogenous retroviruses

[Loudmouth]

Okay thanks for the simplified clarifications.

So please be patient with me because I am going to ask heaps of questions.
But one or two at a time as my brain is already close to overload.

1: Is this imprint in ALL races of humans ?

All humans? Yes. Race is a human contrivance.

2: Clarify Chimp---all monkeys or just the chimpanzee species.
Can't quite make out the imprints in the above picture.
Does it say humans have same imprint as all the types of monkeys ?

Chimps are apes. The easiest way to tell the difference between a monkey and an ape is that apes don't have tails. When we say chimps we mean Pan troglodytes. This is the genus/species name given to chimpanzees. Humans have the same imprints as chimpanzees and gorillas, since we share a common ancestor who also had those imprints. We also share imprints with other apes, and those reflect how far back our common ancestor was. So we will share imprints with chimps and gorillas that are not shared with orangutans, however chimps, humans, and chimps do share imprints with orangutans. The arrows at each branch show the imprints that are shared with branches further down the trees.

3: How do we know it's a virus that made the imprint.

As mentioned above, from the DNA sequence. Also, as is mentioned in the OP, by observing first had the insertion of the sequences due to viral infection in cultured cells in the lab.

 

[Alternate Carpark]

Keep it simple rmwilliamsII....
You may understand what you are saying, but as for me who knows nothing of these things, your post could have been written in binary
and it would have made as much sense.
So ..I'll have to ask the questions again.
And please..no references to techno speak sites,
I'm in here asking questions because people already understand the concept and I would like it explained SIMPLY.


Okay thanks for the simplified clarifications.

So please be patient with me because I am going to ask heaps of questions.
But one or two at a time as my brain is already close to overload.

1: Is this identical imprint in ALL races of humans ?

2: Clarify Chimp---all monkeys or just the chimpanzee species.
Can't quite make out the imprints in the above picture.
Does it say humans have same imprint as all the types of monkeys ?

3: How do we know it's a virus that made the imprint.

 

[Alternate Carpark]

LOL Either you posted just as I was posting Loudmouth, ot I didn't see it.

-- Okay, so it's established that it is a virus because of conducted tests.
-- All races of humans have same identical imprint.
-- The exact same imprint as apes.
-- Concluding a common ancestor.

1: is this imprint in an identical position in ALL humans and ALL apes ?

 

[Phred]

1: is this imprint in an identical position in ALL humans and ALL apes ?

All humans share the same ERVs in the same position on the genome. We share several of these ERVs with chimpanzees that we don't share with any other primates. Both chimps and humans share different ERVs with other primate species.

Humans and chimps share common ERVs with gorillas.
Humans, chimps and gorillas share ERVs with orangutans
Humans, chimps, gorillas and orangutans share ERVs with gibbons
Humans, chimps, gorillas, orangutans and gibbons share ERVs with Old world monkeys
and the entire batch then shares ERVs with New world monkeys.

This shows the order in which the species diverged.

 

[Loudmouth]

Alternate Carpark,

As stated above, the ERV's are in the same exact spot in each of the genomes. The chances of these insertions happening independently of each other is very, very unlikely. The odds for this hapenning have to be in the 1 in a billion range. However, the odds of it happening once is probable, given enough time. If that species then branches off into another species, that new species will also carry the ERV.

Let me see if I can break this down for you. Instead of using the normal designation for viral insertions, I will just use letters. Hopefully this will not intimidate as much. I will also restrict this to humans, chimps, and orangutans. This will hopefully help in visualizing how common ancestory is set up.

1. Humans have ERV's A, B, C, D, and E.

2. Chimps have A, B, C, D, and F.

3. Orangutans have A, B, G, and H.

We then see that all three have A and B in common. Therefore the common ancestor for all three had these ERV's.

We see that orangutans have G and H which are not represented in the other two. These ERV's occured after the split from the common ancestor.

We see that in addition to A and B, humans and chimps also have C and D in common. This means that humans and chimps share a common ancestor after orangutans. These two species branched off after the orangutans line.

Humans and chimps share A, B, C, and D but differe in E and F. These ERV's occured after the split between chimps and humans.

So the tree is constructed like so. Orangutans branch off, leaving us with the orangutan line and the human/chimp common ancestor. Then humans and chimps branch off from their common ancestor. This forms the nested hierarchy that we see when looking at fossils through morphological changes. In fact, the ERV trees that are constructed agree with the fossil record. The important lesson to take away from this is that ERV's and the fossil record are independent measures. That is, the findings in one does not influence the findings in the other field. This is how evolution is tested, corroboration from many independent measures when the evolutionary assumption is applied. If the evolutionary assumption was wrong, then the independent measures would not agree. Therefore, evolution is testable and can be falsified. Comparing ERV's with the fossil record is another example of how evolution has passed scientific tests and is a validated theory.

 

[Alternate Carpark]

Thanks for that, it takes a little while before it sinks in.

Okay so humans and apes have the same ancestor.
Now when you say ancestor, do you mean an ancestorial species or
one singular animal that is the "father" of all the subsequent species ?

I am not trying to compare this to an adam and eve scenario by the way.
Just trying to understand the geneology of it.

 

[Phred]

Okay so humans and apes have the same ancestor.
Now when you say ancestor, do you mean an ancestorial species or
one singular animal that is the "father" of all the subsequent species ?

Both. The ERV insertion happens to one individual. But this ERV is passed down to all his/her offspring.

 

[Jet Black]

Thanks for that, it takes a little while before it sinks in.

Okay so humans and apes have the same ancestor.
Now when you say ancestor, do you mean an ancestorial species or
one singular animal that is the "father" of all the subsequent species ?

I am not trying to compare this to an adam and eve scenario by the way.
Just trying to understand the geneology of it.

It is just an extreme case of the sibling breakdown, where statistically at some point, everyone will be related to one person in some way. This is particularly acute in small populations. If we imagine a small tribe of about a hundred people, who all bred relatively randomly, at some point everyone will be able to say that one of their great great great...... grandparents is the same person, and everyone will share a bit of his genetic code (though there may be mutations in the meantime)

 

[Nim]

For the ERV to be passed down it has to be present in thee sperm or egg that ends up bringing forth a child right? Where does sperm or eggs get there DNA from? That is, when sperm or eggs are created, what is there DNA modeled after? I would imagine that because of random mutations, that everyone has some variations of there original genome present in different places of there body.

 

[Loudmouth]

For the ERV to be passed down it has to be present in thee sperm or egg that ends up bringing forth a child right?

Yes. The ERV has to be inserted into a germ line cell or has to already be present in the genome of the organism at the time of conception. Once the ERV is in the genome it is passed on just like any other piece of non-coding DNA. As an aside, the majority of DNA in the human genome does not code for a protein.

Where does sperm or eggs get there DNA from? That is, when sperm or eggs are created, what is there DNA modeled after?

Sperm are the result of a process called spermatogenesis. Germ line sperm cells divide into two populations. One population goes through a few more divisions and becomes a sperm cell while the other population stays on as a germ line sperm cells and gives rise to subsequent sperm.

Oogenesis, or egg production in females, occurs during development in the womb. A woman in born with all of the eggs she will ever have, and these are stored in her ovaries. Only a small portion of those eggs will ever make their way through the reproductive system and have a chance at reproduction.

I would imagine that because of random mutations, that everyone has some variations of there original genome present in different places of there body.

And we do. Those mutations occur during the process of making eggs and sperms, and so neither parent has those mutaitons in their genome. If I remember correctly, there are about 5-20 mutations per generation. These estimates vary depending if you are looking at non-functional or functional DNA. This is by memory, but I could look it up if necessary.

 

[Peiper]

Wow...

This is my first post. I stumbled into this site and is it refreshing to find scientific discussion in even the darkest corners of the Internet!

Winace I am in awe. Beautiful and succinct analysis. I enjoyed every second!

I look forward to future posts, as I am among brothers!

 

[joelazcr]

It seems the claim is being made when comparing ERV placement between chimps and humans of exactness and identical placement. Where in the scientifc literature is this shown?

Here a paragraph from the paper by Sverdlov, Retroviruses and primate
evolution:

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 classifications 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,(37,41) 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.

It appears the comparison is based on the signature of the binding
sites, and not the viral sequence itself.

 

[ForeRunner]

Could you site your source? I can't seem to find it.

 

[Loudmouth]

Here is an abstract that shows common genome placement of a an ERV (ERV-9 to be exact)

Genomics. 1998 Dec 15;54(3):542-55. Related Articles, Links
[size=+1]A long terminal repeat of the human endogenous retrovirus ERV-9 is located in the 5' boundary area of the human beta-globin locus control region.[/size]

Long Q, Bengra C, Li C, Kutlar F, Tuan D.

Department of Medicine, Medical College of Georgia, Augusta, Georgia, 30912, USA.

Transcription of the human beta-like globin genes in erythroid cells is regulated by the far-upstream locus control region (LCR). In an attempt to define the 5' border of the LCR, we have cloned and sequenced 5 kb of new upstream DNA. We found an LTR retrotransposon belonging to the ERV-9 family of human endogenous retroviruses in the apparent 5' boundary area of the LCR. This ERV-9 LTR contains an unusual U3 enhancer region composed of 14 tandem repeats with recurrent GATA, CACCC, and CCAAT motifs. This LTR is conserved in human and gorilla, indicating its evolutionary stability in the genomes of the higher primates. In both recombinant constructs and the endogenous human genome, the LTR enhancer and promoter activate the transcription of cis-linked DNA preferentially in erythroid cells. Our findings suggest the possibility that this LTR retrotransposon may serve a relevant host function in regulating the transcription of the beta-globin LCR. Copyright 1998 Academic Press.

In this case, the ERV is responsible for upregulating beta-globin in humans and gorillas. The ERV is found upstream of the beta-globin gene in both species, and is very similar in sequence. Kind of cool. It has the same placement in the genome, nearly identical sequence, and provides the same function in both species.

 

[joelazcr]

Here is the Sverdlov reference:

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

This is from the Genomics article about ERV-9:

The ERV-9 family of proviruses contain 30-50 members.

Solo ERV-9 LTRs with a copy number of
3000-4000 have been found in the human genome

One of these repeats is homologous in humans and
gorillas.

"This LTR retrotransposon is conserved with 98-99% sequence identities in people of different races and in the gorilla, except that some people have 11 instead of 14 U3 repeats and the gorilla has only 5 U3 repeats."

So they are not identical or exactly the same.

 

[joelazcr]

The notion that retrovirus insertion is random does not fit the current
understanding.

Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration (murine leukemia virus)
Science 300, 1749 (2003).

Retroviruses have been used as efficient gene-delivery vehicles in many gene-therapy trials. Historically, the integration events of retroviruses were believed to be random, and the chance of accidentally disrupting or activating a gene was considered remote. Recently, 2 of 11 children treated for a rare blood disease with an MLV-based gene-therapy vector developed leukemia at least in part because of independent insertions of the MLV provirus near the same growth-promoting gene, LMO2. Thus, the safety of these treatments has become a primary consideration, and the assumption of random integration is in doubt. Although in vitro integration models have identified many important factors for integration site selection, such as nucleosomal structure and DNA binding proteins, integration site selection in vivo still remains poorly understood, and no consensus sequences have been determined in the primary flanking sequences of target-site DNA. Before the sequence of the human genome was available, it was impossible to obtain an accurate global picture of retroviral integration events. Early in vivo studies have produced conflicting results, with some reporting that transcriptionally active regions are favored for retroviral integration and others reporting that transcriptionally active regions are disfavored. Recently, Schroder et al. mapped over 500 integrations of HIV-1 in the human genome and reported that HIV-1 integration favored genes. Whether this preference is specific for HIV-1 or applies to other retroviruses, particularly MLV, which is a widely used gene-therapy vector, was not known.

The following article in Science also confirms that retrovirus insertions
target specific genomic sites.

Mobile Elements: Drivers of Genome Evolution
March 12, 2004 Science

LTR retrotransposons and retroviruses are quite similar in structure. They both contain gag and pol genes that encode a viral particle coat (GAG) and a reverse transcriptase (RT), ribonuclease H (RH), and integrase (IN) to provide enzymatic activities for making cDNA from RNA and inserting it into the genome. They differ in that retroviruses encode an envelope protein that facilitates their movement from one cell to another, whereas LTR retrotransposons either lack or contain a remnant of an env gene and can only reinsert into the genome from which they came. Reverse transcription of retroviral RNA or LTR retrotransposon RNA occurs within the viral or viral-like particle in the cytoplasm, and is a complicated, multistep process.

"Many LTR retrotransposons target their insertions to relatively specific genomic sites.

The retroviruses HIV (human immunodeficiency virus) and MLV (mouse leukemia virus) share many structural features with LTR retrotransposons. In general, HIV inserts into many sites throughout actively transcribed genes, whereas MLV integrates preferentially into the promoters of active genes. The preference of retroviruses for insertion sites in and around genes may explain the occurrence of leukemia-producing insertions into the promoter of the LMO-2 gene in 2 of 10 patients undergoing retroviral gene therapy for severe combined immunodeficiency."

A retrovirus that naturally infects many nonhuman primate species can easily jump the species barrier to humans and does so frequently among bushmeat hunters in Africa, according to a study published in the 19 March issue of The Lancet.

 

[monkenstick]

The notion that retrovirus insertion is random does not fit the current
understanding.

you are correct that it is not strictly random

this doesn't change the problem for creationists however

Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration (murine leukemia virus)
Science 300, 1749 (2003).

Retroviruses have been used as efficient gene-delivery vehicles in many gene-therapy trials. Historically, the integration events of retroviruses were believed to be random, and the chance of accidentally disrupting or activating a gene was considered remote. Recently, 2 of 11 children treated for a rare blood disease with an MLV-based gene-therapy vector developed leukemia at least in part because of independent insertions of the MLV provirus near the same growth-promoting gene, LMO2. Thus, the safety of these treatments has become a primary consideration, and the assumption of random integration is in doubt. Although in vitro integration models have identified many important factors for integration site selection, such as nucleosomal structure and DNA binding proteins, integration site selection in vivo still remains poorly understood, and no consensus sequences have been determined in the primary flanking sequences of target-site DNA. Before the sequence of the human genome was available, it was impossible to obtain an accurate global picture of retroviral integration events. Early in vivo studies have produced conflicting results, with some reporting that transcriptionally active regions are favored for retroviral integration and others reporting that transcriptionally active regions are disfavored. Recently, Schroder et al. mapped over 500 integrations of HIV-1 in the human genome and reported that HIV-1 integration favored genes. Whether this preference is specific for HIV-1 or applies to other retroviruses, particularly MLV, which is a widely used gene-therapy vector, was not known.

so thats roughly 30,000 possible integration sites, not to mention that the integration can probably occur at many sites within the gene

The retroviruses HIV (human immunodeficiency virus) and MLV (mouse leukemia virus) share many structural features with LTR retrotransposons. In general, HIV inserts into many sites throughout actively transcribed genes, whereas MLV integrates preferentially into the promoters of active genes. The preference of retroviruses for insertion sites in and around genes may explain the occurrence of leukemia-producing insertions into the promoter of the LMO-2 gene in 2 of 10 patients undergoing retroviral gene therapy for severe combined immunodeficiency."

so for HIV or MLV this merely narrows it down to actively transcribed genes, perhaps someone would care to hazard a guess as to how many genes are actively transcribed in the germline (one could use the number of processed pseudogenes as a guide, which, coincidentally, is another evidence of common descent which cannot be explained in a creationist paradigm)

[size=+1][/size] 1: Genome Res. 2003 Dec;13(12):2541-58. Related Articles, Links
[size=+1]Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome.[/size]

Zhang Z, Harrison PM, Liu Y, Gerstein M.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.

Processed pseudogenes were created by reverse-transcription of mRNAs; they provide snapshots of ancient genes existing millions of years ago in the genome. To find them in the present-day human, we developed a pipeline using features such as intron-absence, frame-disruption, polyadenylation, and truncation. This has enabled us to identify in recent genome drafts approximately 8000 processed pseudogenes (distributed from http://pseudogene.org). Overall, processed pseudogenes are very similar to their closest corresponding human gene, being 94% complete in coding regions, with sequence similarity of 75% for amino acids and 86% for nucleotides. Their chromosomal distribution appears random and dispersed, with the numbers on chromosomes proportional to length, suggesting sustained "bombardment" over evolution. However, it does vary with GC-content: Processed pseudogenes occur mostly in intermediate GC-content regions. This is similar to Alus but contrasts with functional genes and L1-repeats. Pseudogenes, moreover, have age profiles similar to Alus. The number of pseudogenes associated with a given gene follows a power-law relationship, with a few genes giving rise to many pseudogenes and most giving rise to few. The prevalence of processed pseudogenes agrees well with germ-line gene expression. Highly expressed ribosomal proteins account for approximately 20% of the total. Other notables include cyclophilin-A, keratin, GAPDH, and cytochrome c.

PMID: 14656962 [PubMed - indexed for MEDLINE]

basically, the fact that insertions prefer actively transcribed genes and their promoters does nothing to alleviate the problem. Its still incredibly unlikely that they would integrate in the same chromosomal location, because the number of possible integration sites is still a huge number. Parsimony rules out the hypothesis that these integrations occured independently in all the separate lineages. Only the most dogged "anti-common ancestrist" would deny that the common descent hypothesis explains the data far better

 

[monkenstick]

"This LTR retrotransposon is conserved with 98-99% sequence identities in people of different races and in the gorilla, except that some people have 11 instead of 14 U3 repeats and the gorilla has only 5 U3 repeats."

So they are not identical or exactly the same.

variable number of tandem repeats , or VNTRs, are commonly polymorphic, due to quirks in DNA replication which are currently beleived to be due to a phenomenon called polymerase slippage.

one can still show the common ancestry of VNTRs however, and in fact, VNTR's are often used in forensic DNA testing. This is because the location and repeated sequence of VNTR's is homologous.

 

[ForeRunner]

/bump

 

[Nim]

Anyone know where to find a list of ERVs? Are the insertions officially named? I'd like to see a list of them and in what species they are found in. I looked around with google but I didn't come up with anything.