ERV FAQ: Don't retroviruses target particular locations in the DNA? Doesn't this explain corresponding ERVs?

https://barryhisblog.blogspot.com/p/relationship-between-integration-sites.html



  1. It would be great if we could use retroviral-like vehicles to precisely target positions in DNA. Think of the possibilities that would open up. It would be a wonderful tool for gene therapy, including cancer treatment, treatment for genetically inherited diseases, anti-viral therapy, genetic engineering, and pure research. That is why retroviral integration has been studied so carefully. Unfortunately, integrase, the enzyme that actually does the integration of a new DNA sequence into the DNA of the host organism, does not target specific loci. Update: Since the writing of the preceding, CRISPR interference has begun to become a powerful "gene editing" tool which has enormous possibilities because it can manipulate DNA in a very precise manner. Of course, CRISPR gene editing does not use retroviral-native integrases.
  2. Actual studies of integration sites include HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modifications and Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences and many others. While the title of the second paper sounds interesting from the creationist point of view, it doesn't help. What these sorts of studies do is to survey real retroviral integration sites, using the same types of cell from the same individuals (identical DNA) in order to find any statistical 'preference' for certain types of area (in an existing gene, not in a gene, near a promoter etc.) Typically, they find some overall patterns, but no repetition of integration sites within 500 samples of the same cell type with the same retrovirus. This is not the locus specificity required to account for 200,000 integrations in precisely corresponding loci. Only common inheritance can account for them.

Yes, we know that ERVs can integrate in certain areas with a statistical preference. But this is not the base-level resolution targeting which would be required to question the endogenization hypothesis. I liken the issue to road traffic accident statistics. Yes, certain stretches are road are more prone to accident to others, but it is extremely rare for a road traffic accident to involve a collision in exactly the same spot and even more rare for them to involve exactly the same vehicles and the same occupants. It's far more likely that you are looking at duplicates of reports of the same accident.You could decide that these accidents were intelligently designed by some malicious supernatural force, or you could decide that the accident statistics are due to the particular road layouts, traffic patterns etc.

Update. Some creationists are putting the crotch area of their trousers under significant strain over their discovery of the discovery (by "evolutionist" scientists, note), of the highly site-specific integration of ZAM, 
a retroelement found integrated with the genome of Drosophila melanogaster (fruit flies), which is very similar in structure and replication cycle to mammalian retroviruses and is highly site-specific. However, as this paper, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527525/ says, "Although different retroviruses have been shown to target distinctive chromosomal regions, few of them display a site-specific integration." The integrase involved is different than that found in retroviruses that have invaded mammalian genomes. Yes, It' is quite an exciting discovery for its potential for genetic research, gene therapy and genetic engineering, but sorry creationist guys, still your throbbing bits. It cannot account for site specificity in us mammals. Only common ancestry can do that.

26 comments:

  1. Of the approximately 90'000 ERVs per haploid genome, only a handful is activated in somatic cells. They are a sessile part of the genome silenced by the piwi-RNAs pathways and direct methylation. Their activity is mainly observed during meiosis, which shows they are the variation-inducing mechanism of the gametes. Each original baranome (the pluripotent, uncommitted genomes of primordial creatures) must have had a number of VIGEs, some of which we still find on the same location in distinct species. In specified baranomes, VIGEs may have been located on the exact same positions (the T-zero location), which then explains why some VIGEs such as ERVs, can be found in the same location in, for instance, primates and humans. Further, sequence-dependent integration of VIGEs in the germ line may be meiosis specific (nobody studied integration mechanisms during meiosis, but merely in diploid cell models during mitosis). Accumulation of VIGEs speeds up over time (due to loss of control of the piwi pathway) and is a major cause of aging.

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    1. Peer, I see that you blog at "Creation Ministries International". Have you signed up to their statement of faith which says,

      "Facts are always subject to interpretation by fallible people who do not possess all information. By definition, therefore, no interpretation of facts in any field, including history and chronology, can be valid if it contradicts the scriptural record."

      Are you an infallible person in possession of all information, such that you can justify this statement? And how can anyone trust you to take an honest, objective view?

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    2. Barry, I am not an infallible person; I merely checked the syncytine claims because from a selcetionsits point of view ERVs and LINEs should not be around and active. And then I made some rather interesting observations. All I ask from you is to read the paper with an open mind. Imo, my hypothesis is better than the one proposed by the evolutionary community because it requires less assumptions and less improbable genetic events.

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    3. "...from a selcetionsits point of view ERVs and LINEs should not be around and active." What makes you say that?

      I've just commented on your paper, BTW. Think about it, Peer. Why would a designer go through all the rigmarole you speculate about? Why not just design features in where it wanted them? Your ideas just don't make any sense.

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    5. here is your problem...as of 2016. research in human and mouse ERV'S titled integration and fixation preferences in mouse and human erv's they found this...."The ERVs in our study are preferentially fixed in areas of the genome where both genes and most conserved elements are scarce (the signal is frequently stronger next to the IntS). There is also a strong preference of ERVs to be fixed in areas with low recombination rates, likely because in such areas they have a lower probability of being removed via ectopic recombination. The initial integration occurs preferentially relatively close to the centromere, likely because of increased AT-richness, and fixed ERVs are located even closer to the centromere, likely because of reduced recombination rates. ETns also show a fixation preference for areas rich in enhancer histone marks (alternatively they might induce the formation of these marks), and this signal is localized at the IntS."

      so similar genomic landscapes CHIMP/MAN will have similar functional expressions thus the same ERV loci in both due to fixation preferences.

      also, all proviruses get their receptors UPON LEAVING the host cells.

      they leave and take pinches of membrane and receptors with them, thus allowing them to get inside other host cells like the one they left.

      the new data shows that viruses ARE ESCAPED VECTORS FROM CELLS, OR VIRUSES ARE CELLS THAT HAVE LOST MOST FUNCTIONS AND ORGANELLES.

      so any model that claims viruses are our creators, or creators of cells, falls apart with the new data.

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    6. It is not "my problem", bob. The evidence indicates what it indicates. Yes, we know that ERVs can integrate in certain areas with a statistical preference. But this is not base-level targeting, which would be required to question the endogenization hypothesis. I liken the issue to road traffic accident statistics. Yes, certain stretches are road are more prone to accident to others, but it is extremely rare for a road traffic accident to involve a collision in exactly the same spot and even more rare for them to involve exactly the same vehicles. You could decide that these accidents were intelligently designed by some malicious supernatural force, or you could decide that the accident statistics are due to the particular road layouts, traffic patterns etc.

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  2. ERVs and LINEs are redundant elements which cannot be kept stable in the genome by selection, so it requires a mechanism to keep them in. That mechanism is autonomous replication independent from the genome. ERVs are mobile genetic regulators to make sure there is variation in the offspring. And LINEs have important function in genome contraction during cell devisions and gene silencing. How it works will soon be published. Further, why-would-the-designer-do-this-or-that-questions are theology, I-m only doing science-questions and leave theology to the theologists. If you-ve read my paper you know that the VIGEs first is the better, more parsimonous explanation. What the evolutionists want, Darwinian atheists in particular, is a almost entirely useless genome, which is such a load of bogus that serious geneticists and evolutionary biologists do not even want to consider this any longer. Most likely, the whole thing was frontloaded, designed to vary, to adapt and to evolve. That-s the best explanation of what we observe. Darwinian arguments all stem from ignorance about biology. Read my papers on the design of life and you will start to understand how it works. Think free, be sceptic.

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    1. I can't read your papers if you don't tell me where they are, "Anonymous". (And I'd rather be skeptic than sceptic, thank you. P) )

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    2. Plos one article as of 2017, on the study of human and rat ERVs, found that insertion was NOT random, but that insertion preference was at adenosine and thiamine rich regions and micro satellite areas with repeat sequence.
      Plos one 2017.We found that ERVs integrate in late-replicating AT-rich regions with abundant microsatellites, mirror repeats, and repressive histone marks. Regions favoring fixation are depleted of genes and evolutionarily conserved elements, and have low recombination rates, reflecting the effects of purifying selection and ectopic recombination removing ERVs from the genome."

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    3. Nobody claims that they are totally random, bmk77k. Site preference has been extensively studied. The point is that, although there is a statistical preference for certain types of regions, such preferences cannot account for the precision, down to base-pair resolution, of corresponding integrations in closely related species. This can only be accounted for by inheritance from common ancestors.

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    4. here is your problem...as of 2016. research in human and mouse ERV'S titled integration and fixation preferences in mouse and human erv's they found this...."The ERVs in our study are preferentially fixed in areas of the genome where both genes and most conserved elements are scarce (the signal is frequently stronger next to the IntS). There is also a strong preference of ERVs to be fixed in areas with low recombination rates, likely because in such areas they have a lower probability of being removed via ectopic recombination. The initial integration occurs preferentially relatively close to the centromere, likely because of increased AT-richness, and fixed ERVs are located even closer to the centromere, likely because of reduced recombination rates. ETns also show a fixation preference for areas rich in enhancer histone marks (alternatively they might induce the formation of these marks), and this signal is localized at the IntS."

      so similar genomic landscapes CHIMP/MAN will have similar functional expressions thus the same ERV loci in both due to fixation preferences.

      also, all proviruses get their receptors UPON LEAVING the host cells.

      they leave and take pinches of membrane and receptors with them, thus allowing them to get inside other host cells like the one they left.

      the new data shows that viruses ARE ESCAPED VECTORS FROM CELLS, OR VIRUSES ARE CELLS THAT HAVE LOST MOST FUNCTIONS AND ORGANELLES.

      so any model that claims viruses are our creators, or creators of cells, falls apart with the new data.

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    5. Again, it is not my "problem". Science deals with the fact, whatever they are. The only "problem" they present is that they require an explanation. See my last reply to your previous comment. A statistical "preference" for certain types of integration site is not the base-level targetting that would be required to give an alternative explanation for apparently orthologous retroviral integrations.

      Re. escaped vectors from cells, of course. The retroviral replication cycle requires a retrovirus to integrate itself into host DNA, in order to induce it to create the requirements of new exogenous virions. Why does this surprise you?

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    6. This comment has been removed by the author.

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  3. "Retroviruses integrate into a shared non-palindromic DNA motif", Nature Microbiology,14 November 2016.

    Seems as if insertion is not random, even down to the base pair resolution level.



    "Evidence for DNA Sequence Encoding of an Accessible Nucleosomal Array across Vertebrates", Biophysical Letter, May 22, 2018.

    Also an interesting article about Alu integration. "Evidence of a strong association between NIEB borders and the polyA tails of ALU sequences in human. These results suggest that NIEBs provide adequate chromatin patterns favorable to the integration of ALU retrotransposons and, more generally to various transposable elements in the genomes of primates and other vertebrates".

    Seems like integration of ERVs and ALUs is less random than previously thought.

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  4. Where in your first article do the authors state that insertion is non-random down to the base pair resolution level? In fact, the opposite seems to be true. From the article:

    "It was previously assumed that the non-appearance of the palindromic nucleotide sequence in individual retroviral integration sites was due to the fact that the palindrome was weak, i.e. poorly conserved. However, in the present study we found evidence that the palindrome was statistically significantly disfavoured at the level of individual sites: the palindrome is evident only as an average – a consensus – of the population of integration sites."

    This confirms previous conclusions that insertion is not locus-specific. See for example in the paper "Weak palindromic consensus sequences are a common feature found at the integration target sites of many retroviruses."From this article:

    "While integrase has strict sequence requirements for the viral DNA ends, target site sequences have been shown to be very diverse."

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  5. In 2016 I wrote: "And LINEs have important function in genome contraction during cell devisions and gene silencing. How it works will soon be published."

    In 2017, my prediction was indeed confirmed. Nature genetics reported that the "activation of LINE-1 regulates global chromatin accessibility at the beginning of development and indicate that retrotransposon activation is integral to the developmental program." Nat Genet. 2017, 49(10):1502-1510


    Peer Terborg, aka Peter Borger.

    My book Darwin Revisited is now available at amazon:
    https://www.amazon.de/Darwin-Revisited-understand-biology-century/dp/6202315113

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    1. I will happily read and review your book if you send me a review copy. (I only buy creationist books second-hand so as not to encourage them). My email address is my name with a dot in the middle at gmail dot com. Mail an electronic copy to me or mail me to ask for my postal address.

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  6. I don't know why you are pimping your book here, "Peer". This page is about alleged "targetting". Many other pages in this blog deal with the creationist bleat that there is function in many retroelements, for example, https://barryhisblog.blogspot.com/p/skip-to-content-es-evolution-news.html Why would there not be?

    As for your book, there is only one comment on amazon.com at present. https://www.amazon.com/gp/customer-reviews/R3L1L6RSEMX9G8/ref=cm_cr_dp_d_rvw_ttl?ie=UTF8&ASIN=6202315113

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  7. Shared ERVs in exactly same locations or not, they don't actually confirm that humans were once tailless monkeys.

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    1. Primates. Only common ancestry can explain common loci.

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    2. "Primates. Only common ancestry can explain common loci."

      Only from the point of view of evolutionist a.k.a atheists, which is nothing more than an opinion.

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    3. Can't you read? Surveys of integration sites show that there is no precise targetting. That is not opinion. It is a fact. And what's all this rubbish about "evolutionists" and "atheists". This is science. Not theology.

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    4. "Surveys of integration sites show that there is no precise targetting. That is not opinion. It is a fact."

      Depends on the perspective. With respect to randomness, it is not random. With respect to precision, it is not fully precise. Just like there is no such thing as 100% perfectly straight line in reality. This is common sense.

      Thousands, etc. shared loci didn't mean anything. It is like the chance of mosquitoes biting similar particular spots on the skins of two different men will be unlikely, unless if there is something that is holding the mosquitoes to bite only the partcular spots on the skin on two different men and unless if someone put something on only particular spots on their skin that will attract the mosquitoes.

      Common loci or uncommon loci, doesn't matter. What's matter is the result.

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    5. There is not much more I can say to someone who is in flat denial of reality.

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    6. "There is not much more I can say to someone who is in flat denial of reality."

      Objectively speaking, reality is consisted of the finite and infinite, and everything changes. Other than these are just mere opinions.

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