Intro to ERVs: LTR GATOR!

So Ive been over the basics of ERVs (Intro, gag, pol, env), but Im still missing a ‘basic’ aspect of ERVs, even though I talk about them all the friggen time on this blag: LTRs.

In exogenous retroviruses, LTRs act as promoters. Genome has all the genes (gag, pol, env), LTRs make sure they, and genomic RNA, is made. But just as a side-effect of the reverse transcription process, every integrated retrovirus (provirus) has two identical LTRs, U3-R-U5. A viral genome just has an R-U5 on the 5′ end, and a U3-R on the 3′ end.


So, two promoters– One at the 5′ end, making virus, and one at the 3′ end… making… ?

This is one of the ways that retroviruses can cause cancer. Just due to chance, the retrovirus inserts just upstream of an oncogene. Throw an active promoter upstream, you get cancer. Ek.

Well, when dealing with ERVs, obviously ERV LTRs 5′ of an oncogene would be detrimental, thus not passed on.

But that doesnt mean that ERV LTRs arent contributing at all to gene expression. Assuming an ERV plops down upstream of a random gene, the LTR could:

  • Be silenced epigenetically, or through mutations– nothing happens
  • Provide an alternative promoter for, up/down regulating gene expression, tissue specificity
  • Provide an alternative start site, creating an isoform of coded protein, or an alternative ORF

These little variations endogenous LRTs cause, in protein structure or protein expression, could be a huge driving force behind speciation and diversity! (microRNAs have a role in this too!)

Well, weve got a minor problem trying to address the impact of LTRs on gene expression in humans. We do, like, these huge data mining experiments which tell us “OMG LIEK THEIR ALL ACTIVE!”… but then you have to go back by hand to figure out whether the LTR activity is random noise, a minor contributor to gene expression, creating an alternative protein, or the sole promoter for the gene.

A review was just published that consolidates a lot of what we know about ERV LTRs and human genes.

Endogenous retroviral LTRs as promoters for human genes: A critical assessment.
Available data suggest that, while new expression patterns can arise as a result of LTR usage, this situation is relatively rare and is largely restricted to the placenta. In many cases, the LTR appears to be a minor, alternative promoter with an expression pattern similar to that of the native promoter(s) and hence likely exerts a subtle overall effect on gene expression.

AWWWWW. MAN! Bummer!

I was hoping they were gonna be all like “ERV LTRs are why humans are human and mice are mice!” That woulda been so cool!!

While there are some human genes that have totally co-opted ERV LTRs for their expression, there arent very many. And the LTRs that make alternative promoters are pretty minor. Man.

Alas, just like everything in science, and biology, and evolution, its just lots of little changes. Little changes that contribute towards big differences. Nothings the superstar.

Comments

  1. #1 Sili
    July 16, 2009

    I almost think I understood that.

    If only I wasn’t distracted by thinking “litigator”.

  2. #2 Cath@VWXYNot?
    July 16, 2009

    w00t – that paper’s from my old lab and references some of my papers!

    I was a wee bit disappointed by the conclusions the first time I heard them too, but hey, that’s science ;) I’m just glad I got to work in that lab while there were still some cool examples to play with.

  3. #3 lithopithecus
    July 18, 2009

    “Well, when dealing with ERVs, obviously ERV LTRs 5′ of an oncogene would be detrimental, thus not passed on.”

    couldn’t they (be passed on)?
    if the effects of the upstream insertion manifest themselves later in the organism’s life history
    (as in after reproductive maturity and, presumably, reproduction)?

    this could render them “blind” to selection, right?

    respectfully,
    long-time reader, first time de-lurker.
    (ducks)

  4. #4 Cath@VWXYNot?
    July 20, 2009

    That’s a really interesting point, and I suspect Abbie will give you an interesting answer! My first thought was that in most cases, upregulating an oncogene WILL have detrimental effects early in life, but I have no evidence to back up that assumption. Abbie is much more up to date with the literature than I am!

  5. #5 Matthew
    July 20, 2009

    Mucho interesting… thanks for sharing this, Abbie.

    Kind of a noob question here, I’m new to ERV’s

    Is a provirus and an Endogenous Retrovirus the same thing? Just interchangeable names? Or are they fundamentally different? Cheers

  6. #6 W. Kevin Vicklund
    July 20, 2009

    A provirus is a virus that has inserted itself into the cellular DNA.

    An ERV is a kind of provirus, sp. one that has inserted in a germ cell line and has been passed on to further generations.

  7. #7 ERV
    July 20, 2009

    Blog readers learnin! FUCK YEAH!

    *high-fives Kevin*

  8. #8 Matthew
    July 21, 2009

    Thanks very much Kevin!

    *three-way high five*

  9. #9 Athena Andreadis
    July 23, 2009

    Of mice and (hu)mans: miRNAs, alternative splicing… and the occasional species-specific gene.

  10. #10 Aaron
    October 18, 2010

    What is the difference between an ERV LTR and a the LTR of a non-viral retrotransposon?

  11. #11 Aaron
    October 21, 2010

    Any thoughts? If you find a lone LTR in our genome, how do you know if it is from an ERV or a LTR retrotransposon?

  12. #12 Aaron
    October 30, 2010

    anyone? anyone?

  13. #13 W. Kevin Vicklund
    October 30, 2010

    Pro-tip: if you comment on a year-old post, chances are nobody is going to notice. I only noticed because Saturday mornings are very low traffic on this blog.

    Answer: The structures are different. I know from reading papers they are different, but what the difference is has not been pointed out in any of the references. Note that I’m not an expert.

  14. #14 Justicar
    December 2, 2011

    I’m writing this from the future to tell you that in a couple of years we’ll discover faster than light neutrinos. Oh, and you’ll write a mean blog article about PZ and link to this to show people PZ doesn’t understand your field.

    I can’t say anything more so as to preserve the timeline.

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