7
$\begingroup$

The ability for gene drives to sidestep the Mendelian mechanism and rapidly spread through populations (even if the gene is slightly fitness reducing) is extremely powerful. Why aren't normal populations riddled with parasitic gene drives? What mechanism keeps naturally occurring gene drives suppressed to (apparently) very low levels?

$\endgroup$
11
  • 3
    $\begingroup$ You are going to need to provide references to back up the claim in your first sentence. If you mean this, it is because you need to edit the genome of the organism in order to accomplish the task. $\endgroup$
    – AMR
    Nov 28 '15 at 16:14
  • 1
    $\begingroup$ Yes, by "gene drives" I mean "gene drives". As described by Wikipedia. To introduce new artificial gene drives you need to edit the genome of organisms. But gene drives also occur naturally. (Mentioned here, for example.) The question is, why don't these dominate? Edits made artificially by experimenters can also occur naturally. (Or if they can't, why?) $\endgroup$ Nov 28 '15 at 16:52
  • $\begingroup$ From what they are describing, this is double-stranded break repair. You need a break to occur in the locus of the gene for it to happen. And as only about 1.5% of the human genome is protein coding, random breaks are more than likely not occurring in genetically important regions. For it to happen non-randomly you need an endonuclease to make a break in the chromosome. There are a few examples or genes where this occurs naturally, but more often times you see it as a viral mechanism to integrate into the host chromosome. It is estimated that upwards of 8% of the human genome is viral DNA. $\endgroup$
    – AMR
    Nov 28 '15 at 17:14
  • 1
    $\begingroup$ OK, but double-stranded breaks occur naturally, and you only need a handful (or even one) gene drive created through chance to take over a population. $\endgroup$ Nov 28 '15 at 17:19
  • 1
    $\begingroup$ Ok, you have started to sketch an answer, but its still not at all clear that those suppressive effects are nearly sufficient. Analogously, there are many ways that cells repair DNA and protect against cancer, and if you just listed those mechanisms and said "therefore it's highly unlikely cancer will ever develop", you'd be wrong. In the case of cancer, one can argue that the suppressive mechanisms will drive the rate to be low enough to allow procreation, but for gene drives there is no such argument (unless you go with group selection). $\endgroup$ Nov 28 '15 at 20:57
3
$\begingroup$

I have a feeling that the OP is confusing naturally occurring so-called selfish, or parasitic genetic elements and the CRISPR/Cas9-based gene drives that have been making news as potential tools to eradicate disease vectors like the aedes mosquito. My answer is working from that assumption.

The big difference between naturally occurring "parasitic" genetic elements (including bacterial CRISPR elements and things like transposons) and the gene drives that are being tested as vector control revolves around what we put inside the latter class of gene drive.

The OP hit on this difference in his question, when he mentioned the decrease in fitness caused by engineered drives. In the naturally occurring drive-like elements, there is rarely ever a decrease in fitness in the organism and when it does occur, it is unlikely to be passed on to future generations.

Transposons, for instance, are largely active in somatic cells, whose DNA is not passed on to descendants. Semi-randomly occurring genetic changes are sometimes passed on, but this is relatively rare and evolution favors those that are either neutral or that increase fitness. A brief search doesn't turn up, and I can't think of, any cases of naturally occurring deleterious genetic alterations caused by something like a transposon having been found to remain in a population long enough to be studied.

Engineered gene drives, on the other hand, particularly in the cases of those meant to combat mosquitos, are purposefully designed to reduce the fitness of their target host.

The last question, of what keeps naturally occurring drives at low levels, requires either a rather vague, or a very long answer. I'll go with vague and provide some links to longer ones. Briefly, our genomes have evolved a lot of ways to maintain genomic integrity, in the forms of proteins responsible for proof-reading DNA, repairing breaks, and destroying any "free" pieces of DNA found outside of a chromosome. We've also evolved a lot of mechanisms to maintain genomic integrity through small non-coding RNAs.

Here are some good papers (without paywall) on the subject:

  1. How p53 restrains mobile genetic elements

  2. Proteins that function to restrain mobile genetic elements in rice

  3. Good review of transposons in general

  4. Finally, how people are engineering gene drives to combat malaria

Hope that helps!

$\endgroup$
4
  • $\begingroup$ Thanks very much for your answer. In my defense, I don't think I confused anything so much as I just didn't state my question in the standard terminology. This obviously is not my field, so thank you for filling in the gaps of my knowledge and answering the clearer version of my question. Your paragraphs 2-5 point out that most naturally occurring parasitic gene elements have neutral, rather than negative, effects on fitness. This is useful to know and much appreciated, but of course it just makes my question more pointed. $\endgroup$ Mar 9 '16 at 20:36
  • $\begingroup$ Paragraph 6 sounds to be essentially the sketch of an answer described by AMR in the comments on my question. It may be that there simply isn't a clean, precise answer known. But, as I pointed out there, an analog of this sort of argument exists for cancerous mutations, yet cancerous mutations are common. And it does not explain the essential mechanisms by which lab-engineered gene drives can avoid these natural protections which are apparently so effective against natural parasitic genetic elements. $\endgroup$ Mar 9 '16 at 20:36
  • $\begingroup$ @JessRiedel - sorry for the radio silence. With respect to your original question, I wouldn't think of cancerous mutations as a 'gene drive'. Most cancers only occur after child-bearing age, so doesn't have much of an effect on an organism's fitness. That holds for both hereditary and acquired mutations, the latter requiring a long time to develop. Exceptions, like childhood leukemias, are interesting but quite rare. $\endgroup$
    – Forest
    Mar 11 '16 at 13:37
  • $\begingroup$ Regarding lab-engineered gene drives, I doubt that they avoid cellular defenses, although it would be hard to measure that. Essentially, they overcome defense mechanisms by being targeted to a specific site and by carrying active payloads. That is, when they integrate, they do so in a functionally important location and deliver genetic code that has a measurable effect. This does not hold for many transposable elements. Although sometimes an endogenous TE gets lucky: the-scientist.com/?articles.view/articleNo/32298/title/… $\endgroup$
    – Forest
    Mar 11 '16 at 13:42

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.