A common variant linked to chromosomal errors

A new paper in Science (Rajiv McCoy as main author) says that there’s a genetic variant, probably in the gene PLK4, that substantially increases the fraction of embryos with screwed-up chromosomes.  Mothers with the high-risk genotypes apparently have fewer embryos that survive to 5 days. And, oddly enough, the variant causing this is quite common – spread all over the world, in the 20-45% frequency range.  It looks as if it’s the product of a old partial selective sweep in humans ( Neanderthals don’t seem to have had it).  PLK4 regulates centriole duplication, a key component of the centrosome cycle.

So far so good – a nice piece of work. But then they try to explain it.

Their idea is that reducing fecundability was itself advantageous, because it obscured paternity. I don’t believe a word of it.

First realize that the selective cost isn’t as high as you might think: generally people could only feed a couple of kids anyhow. Taking an extra month or two to start that kid is a cost, but not as big as the fraction of embryos lost might make you think. On the other hand, there would be a big selective advantage for a genotype that was resistant to these pro-aneuploidy alleles..

I’d bet on meiotic drive. Intragenomic conflict.  Not crazy for a gene involved in the centrosome:  centrosome genes associated with meiotic drive have been seen in Drosophila.

If the aneuploidy allele was transmitted to, say, 54% of the offspring of a heterozygote mother, it could work.

There would of course be a net disadvantage in homozygotes, because A. the aneuploidy is worse and B. the allele is competing with itself – so winning is impossible.

With a net disadvantage in homozygotes, the sweep never reaches 100%.

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23 Responses to A common variant linked to chromosomal errors

  1. Rick says:

    The idea that concealed ovulation and constant receptivity were selected because they obscure paternity, and so evolved to increase paternal investment in offspring is very dubious, and likely backwards.

    This would just as likely select for males with a constant drive to have sex at any time with any female, and never believe that the offspring were their own, and then not care for them.

    Much more likely would be that selection for obvious ovulation at a specific time was strongly weakened once people started to wear clothing and control fire. Just like selection for most of our body hair would be lost. It is just no longer necessary or effective. Human babies born at any time of the year are equally likely to survive, so extremely strong selection to become successfully pregnant (with an embryo lacking chromosome abnormalities that will more likely come to term) within a specific two week period is eliminated.

    Because of the loss of ovulation signaling, males might then be later selected for more monogamous behavior, because this might increase the likelihood that the children were his.

    If this polymorphism was actually selected instead of hitchhiking, then I would suggest a different mechanism for the selection. It may be that a bit of aneuploidy is actually helpful in somatic tissues in general, but usually is constrained by the strong selection during seasonal reproduction.

    Or maybe it could reduce the chance of early lethal cancer? Inhibitors of this protein are effective anticancer drugs.

    Or maybe something else.

  2. eurogenes says:

    Cochran, what are your thoughts on this?

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122384

    So, an entry of the LP allele into Europe from northwest Africa (with the pre-proto Bell Beakers?) and then a major expansion with the early Beaker Culture…then a back-migration to the west of mixed Beaker/Yamnaya groups carrying R1b?

    Btw, we now have lots of samples from the Yamnaya horizon, and it looks like they made cheese, or something.

    http://ubm.opus.hbz-nrw.de/volltexte/2015/3975/

  3. melendwyr says:

    So it’s a little bit like the gene for sickle-cell anemia, just with no benefit, and a little bit like the t-gene in mice, only not so pernicious. It continues to exist because it’s good at perpetuating itself from one generation to another, even though it hurts the chances of the organisms’ survival. A genetic parasite, a truly ‘selfish’ gene.

  4. Allow me to play devil’s advocate. I honestly don’t know why this gene is at a 25 to 40% frequency but I see validity in the following hypothesis. As we all know should know pair bonding is incredibly important in the successful raising of children. Men are a testy bunch prone to getting awfully damned snotty if they don’t get their poontang on a regular basis. Women cant get pregnant too frequently, we have evolved a singularly high spontaneous abortion rate in order to keep couples together. This gene is simply a mechanism for a high spontaneous abortion rate. It is as Razib over at Gene Expression Blog has proposed here http://www.unz.com/gnxp/human-uniqueness-is-not-unique/ a type of balancing selection. It hasn’t gone to fixation, it has been stuck in an intermediate range for a very long time.

    • Henk says:

      Or it could just be that spontaneous abortion is part of a quality control strategy. Nursing a human to maturity is frightfully expensive after all. If there is no single best strategic balance of quality-control versus fecundity, different strategies would co-exist at some equilibrium.

      • gcochran9 says:

        Inducing chromosomal errors – which almost always kill the embryo – is a funny way of checking quality.

        • Henk says:

          Oh, but that’s just the abortion mechanism. It obviously isn’t deployed for 100% of carrier’s embryos, so what guards against it, what promotes it: are these factors related to embryonal quality, chance of making it to maturity, chance of eventual procreation?

          • gcochran9 says:

            Whether you know it or not, you’re positing that a fucking SNP, by itself, can judge embryonal quality and then be the chooser of the slain.

          • Henk says:

            As long as we agree to apply sane interpretations to gene-as-agent metaphors: Yes.

          • Henk says:

            Might be wrong. OTOH, how could a puny 12 minute paper-and-pencil test, by itself, pretty accurately predict probability of academic success? Preposterous.

            • gcochran9 says:

              There’s a lot more information in an IQ test than in a SNP. I remember a similar idea by David Haig. He was saying that mothers should be selected to spontaneously abort babies whose expected fitness is sufficiently low, that the cutoff would be different from the mother’s POV than that of the baby’s, thus maternal-fetal conflict. Thing is, the chromosomal abnormalities and the ensuing fetal losses are in fact the only thing we know is happening: he’s assuming that those losses are more likely in a fetus that is in some sense low-quality, but there’s no evidence for that. It’s something he imagined to make high fetal losses fit his theory. The only thing that we know is low-fitness about those fetuses with aneuploidy is the aneuploidy itself.

              • gcochran9 says:

                You might think that quality might go down when the mother is at the edge of starvation: but I know of no hint that aneuploidy goes up in such circumstances.

          • Henk says:

            Thanks for the reply.

            BTW, I misunderstood your previous remark and actually agree that an SNP is too information-poor to set up a scheme like this all by itself. To stay with the IQ test analogy, we’re not looking at the test itself, but at the adjustment of some cutoff score or difficulty parameter for admission at school A to be different from the one used at school B, in the sense there may well be “no single best strategic balance of quality-control versus fecundity.”

            Plausible reasons for extra harsh QC at the cellular level in humans are human longevity, long time to reach sexual maturity, or special susceptibilies of neuronal tissues. (To quote something random off the internet: “Mental impairment is a characteristic feature of all recognizable autosomal aneuploidy syndromes” and “Cortical progenitors undergo 11 rounds of cell division in mice, at least 28 in the macaque, and probable four more in human. This phylogenetic prolongation of mitotic activity provides the basis for a potentially higher rate of accumulating mitotic errors during neurogenesis.”)

            If yanking up some risk factor for aneuploidity during early fetal development is a QC mechanism, we’d want its effect to vanish at a later point. Carriers should have higher miscarriage rates but otherwise equal or lower rates of aneuploidy related defects in order for this to make sense.

    • gcochran9 says:

      Dave, you’re destroying my mind. I can feel it.

  5. The fourth doorman of the apocalypse says:

    Their idea is that reducing fecundability was itself advantageous, because it obscured paternity. I don’t believe a word of it.

    Speaking of reduced fecundity, what’s with Presidents of the US and their wives? Nominally the most powerful men in the world and yet they do not seem to have Temujin-like reproductive success. Must be a genetic abnormality there.

  6. The fourth doorman of the apocalypse says:

    Their idea is that reducing fecundability was itself advantageous, because it obscured paternity. I don’t believe a word of it.

    Promiscuous females seems like an easier path to obscured paternity. I think there is even an example or two out there.

  7. Greying Wanderer says:

    If it’s in balanced selection then mustn’t it prevent something worse often enough to balance out and if so mustn’t that something worse relate to the negative consequences of a) being pregnant or b) a successful pregnancy?

    Things like
    – variable food supplies
    – two well-fed kids vs three underfed
    – high mobility
    etc might relate but hard to see how the same wouldn’t apply to Neanderthals.

    So under what circumstances would a pregnancy be worse that wouldn’t also apply to Neanderthals?

    (or have already worked itself out of Neanderthals?)

    Something to do with farming or male provision?

    If there was an environment where the females could feed their kids themselves and male provision was a casual bonus then that might lead to one set of sexual traits.

    If such a population then moved into a region where male provision was required and so the population gradually moved to pair bonding and monogamy then some of those earlier traits might need to be selected against or at least compensated for

    faithful and fertile
    or
    unfaithful with erratic fertility

    ?

  8. gothamette says:

    Rajiv McCoy? The real Rajiv McCoy, or a fake?

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