Quotes of interest - ERVs.

It has been quite some time since the last update to the Quotes of interest series on junk DNA. Most of the posts have sought to demonstrate that the exhausting cliché that scientists dismissed possible functions for non-coding DNA until recently is false. Therefore, I have provided many quotes indicating that many (if not most) biologists continued to consider possible functions for various non-coding elements throughout the mythical period of neglect. This time, I want to discuss an example in which a particular kind of non-coding sequence was considered as probably non-functional — but because of knowledge about its biology, not because no function could be imagined.

The elements under discussion are endogenous retroviruses (ERVs) which, as the name suggests, are viral-like sequences that exist within the genome. Depending on who you ask, they are either very similar to or are interchangeable with long terminal repeat (LTR) retrotransposons. ERVs make up approximately 8% of the human genome, while LTR elements account for 50-80% of the maize genome.

Endogenous retroviruses were discovered in the 1960s and 1970s (see Weiss 2006), but were first dubbed “endogenous viruses” by David Baltimore in 1974 (published in Baltimore 1975).

Here is how Baltimore (1975) explained their origin:

Evidence has accumulated that viruses have entered the germ line at various times during the ancestry of different species. For convenience, two different cases can be considered: acquisition of viral genomes during inbreeding or domestication and acquisition of viral genomes during the evolution of a species. In principle, viruses could have become part of an animal genome at any stage of evolution and still be detectable now.

Baltimore (1975) discussed the fact that these “endogenous viruses” generally do not grow well in the species in which they had been identified, and that they often show signs of degrading by mutation. Moreover, being clearly similar to viruses and sometimes causing diseases, it seemed very unlikely that they were maintained because they conferred some functional advantage to their hosts. As he concluded,

It is my guess that these viruses have no positive function to play in the life of the animals in which they are resident. Rather, there is an evolutionary equilibrium balancing their acquisition and loss. The viruses are being inserted into the germ line at very low frequency, after which they require many thousands or millions of years to be mutated away because they have little or no detrimental effect on the animal in which they are resident. Viruses that did have a detrimental effect would be lost rapidly and might never come to our attention.

It is worth noting that Baltimore (1975) does not cite Ohno (1972), makes no reference to “junk DNA”, and reaches a tentative conclusion about lack of function from his consideration of the origin and properties of the elements.

Today, some examples are known of ERVs with beneficial effects, such as in placental development (Mi et al. 2000) and p53 binding sites (Wang et al. 2007). (Note, however, that only 0.5% of identified ERVs are associated with binding sites). As Weiss (2006) summarized the present situation:

As Mendelian elements, retroviruses must be subject to host selection. However, with the exception of enrolling env genes in placental differentiation, ERV appear to be parasitic DNA sequences for which the host has little use, other than to protect against further retrovirus infection. Potentially, ERV can damage the host by mutational insertion and by homologous recombination. But despite a tendency to implicate ERV in many ‘non-infectious’ diseases in humans, there is scant evidence that they play a significant role. There are only rare examples where a recessive single gene disorder in a family lineage is caused by an endogenous retroviral insertion disrupting gene function.

Seems like Baltimore’s (1975) assessment was largely correct with regard to mammalian ERV sequences.

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Baltimore, D. (1975). Tumor viruses: 1974. Cold Spring Harbor Symposia on Quantitative Biology 39: 1187-1200.

Mi, S. et al. (2000). Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403: 785-789.

Wang, T. et al. (2007). Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proceedings of the National Academy of Sciences USA 104: 18613-18618.

Weiss, R.A. (2006). The discovery of endogenous retroviruses. Retrovirology 3: 67.

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Part of the Quotes of interest series.


3 comments to Quotes of interest – ERVs.

  • Pellionisz

    “mythical period of neglect” of JunkDNA?

    I have received *today* this answer to my friendly letter to Larry:

    From: “Laurence A. Moran” sandwalk_bioinfo.med.utoronto.ca
    To: “Dr. Andras J. Pellionisz” cob_helixometry.com

    “… Even if all the regulatory regions added up to the size of the average gene they would still only account for a few percent of non-coding DNA as I explain on my blog. [His latest guestimate, prior to Lander et al. fresh paper, was 46%, a whole lot more than “a few percent” – yet in his “guessing game” he entirely missing the point – going for revealing algorithmic principles of genome regulation – AJP]

    Most of our geneome [sic – ol’ Larry is loosing his marbles – I have reasons to do such SNiP-s since English is my sixth language – AJP] is junk.

    Learn to deal with it.

    Best,
    Larry Moran”

    This is the same ol’ Larry who publicly calls me a “kook” on his blog (purposefully – exactly as Barbara McClintock was also called a “kook” by her moron denialists for 40 years for her to get her Nobel.)

    Heads up, Ryan:

    Libel is:

    “An untruthful statement about a person, published in writing or through broadcast media, that injures the person’s reputation or standing in the community. Because libel is a tort (a civil wrong), the injured person can bring a lawsuit against the person who made the false statement.”

    With the new generation of “regulatin’ genes” Larry is about to hit by a ton of bricks falling on him from all directions.

    Wanna be with stuck with him?

    Even if we all were full of junk, like Larry seems to be, I may be able to “learn to deal with it”. However, those dying with “junkDNA diseases” will suffer miserable deaths – for negligence by those like and old hold-out moron.

    pellionisz_atandbeyond_junkdna.com

      (Quote)

  • Anonymous

    “However, those dying with “junkDNA diseases” will suffer miserable deaths – for negligence by those like and old hold-out moron. “

    Right…

    I liked the implicit threats of frivilous lawsuits to silence your critics – I wonder what such antics are a sign of?

    And boasting of how many languages you speak? Oh my goodness, how can you POSSIBLY not be right about your ‘fractogene’ stuff and your historical revisionism re: ‘junkDNA’!

    I mean, anyone who speaks so many languages MUST be right about everything!

    That being the case, I have to wonder why you never did answer any of TRG’s questions…

      (Quote)

  • ERV

    1. You arent a kook, dude. Youre a figgen nutbar.

    2. ERVs are junk. Thats a good thing. Because we know what happens to people when they have active retroviruses in their body. Its called AIDS. And cancer.

    Nutbar.

      (Quote)

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