Foreign Drivers

Generally, a given nuclear allele has a 50% chance of showing up in an offspring.  But sometimes this is not the case –  some cut in line, and having a >50% of  transmission. Such an allele tends to increase, even if it gives no advantage to the organism carrying it.  In some case such an allele can become common, or even go to fixation (100% frequency) while reducing fitness.

The best-known example is the t-allele in mice.  It is transmitted well over 50% of the time,  but never goes to fixation, because male mice with two copies are sterile.

Sometimes  driving genes involve the centromere, a region at the pinched waist of each chromosome that plays an important role in directing chromosomal movement in meiosis.  The cheating opportunity results from the fact that there are four cells produced in female meiosis – the egg and three polar bodies that go nowhere.  A change in the centromere that increased its chance of ending up in the egg, rather than the polar body, would give it a big transmission advantage. The rapid rate of adaptive evolution seen in centromeres makes many suspect that centromeric drive occurs fairly often.

There are probably associated costs in some cases.  Meiosis might be messed up to an extent in males, or a deleterious gene variant might exist near the driving centromere and be  carried along with it.  Over time,  you would expect other genes to change in ways that minimized those costs.

A driving centromere that hadn’t been around long would show the usual signs of recent selection and might still be causing noticeable trouble.  One that been fixed for a long time would be hard to detect, and probably wouldn’t cause much trouble.

This has all been an introduction – the question is, what would happen if we admixed with a long-isolated group of archaic humans that had their own driving genes?  We were similar enough that such genes would probably have succeeded on an AMH genetic background.  If current thinking is correct, and there were several such admixture events in the last 50k years or so ( Neanderthals, Denisovans, and the unknown, highly divergent group in Africa (Mangani !) ),  such sweeps might be easy to see, and negative effects might also still exist and be detectable – the Revenge of the Neanderthals.

Partly I wonder about this because of the anomalously low success rate of human fertilization.  It’s very unusual and nobody yet has an any explanation.  Partly, also, because there is a version of 6.5 megabyte stretch across the centromere of the X-chromosome that is common in Africans and way more divergent than than any other  large chunk of the human genome. There have also been claims of sweeps in  the centromeric regions on several chromosomes in Eurasians.

If this happened to be true, it would also imply that gene flow between  the two groups question would have had to have been extremely low [zero, most likely] for a long long time, since even a wee bit would be enough to transmit something like this, whose success probably would not depend much on local factors like climate or ecology.

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15 Responses to Foreign Drivers

  1. Interesting, what you say about the anomalously low success rates of human fertilization. A cursory google search doesn’t seem to find any corroboration on this, however. Can you recall your source for this?

    • gcochran9 says:

      Fecundability is defined as the probability of a pregnancy in one ovulatory cycle.

      “The human female has a very low fecundability rate, 25% at the age of maximum fecundity.
      In mathematical models on populations, demographers use a mean interval of 7-8 months after constitution of couples (without contraception). ”
      Pre-Eclampsia: Etiology and Clinical Practice F. Lyall, Michael A. Belfort – 2007

      “Human fecundability is very low when compared to the fertility of domestic animals.”
      Maternal Recognition of Pregnancy – Ciba Foundation Symposium, 2009

      And the rate of fetal loss in pregnancy (mostly early pregnancy) is also very high. A lot of that seems to be caused by chromosomal abnormalities.

      • Very interesting stuff, Greg.

        My instinct is to search out similar primates, and to compare ourselves with them. Domestic animals are one thing, primates another.

        * BABOONS
        “Seventy per cent of the sexual cycles of multiparous female baboons are nonconceptive (Gesquiere et al., in press); that is, the female has a complete and apparently normal sexual cycle and mates repeatedly but does not conceive an offspring (interestingly, this value of 70% re- flects a fecundability not dissimilar to women in industri- alized societies, for whom median time to conception is between two and three cycles, reflecting a higher than 50% rate of cycling without conception; Tuntiseranee et al. 1998; Axon & Hagmar 2005). The frequency of nonconceptive cycles is much higher for adolescent female baboons (Gesquiere et al., in press).”

        Click to access Albertsetal_paternity.pdf

        * CHIMPS
        If you scroll down to “Heterogeneity and Fertility”, there’s a nice graph of fertility rate. Seems they’re also at ca. 25-30%.
        http://www.pnas.org/content/107/suppl.2/8977.full

        *
        If chimps and baboons are indeed comparable in fecundability, this might imply that low fecundability is a primate thing, rather than a recently-hybridized-human thing, yes?

        Even if so, this does nothing to refute the broader thrust about driving genes and negative effects thereof, which is pretty plausible. Reduced fecundability is only one of many phenotypes that could result.

      • dave chamberlin says:

        The low rate of human fucundability has never suprised me. Not only do our closest relatives have a low rate as redzengenoist has kindly pointed out it seems obvious to me at least that a lot of sex helps build the pair bond and the male is very much needed in raising the next generation but it would be a terrible burden on the women if she got pregnant on a more frequent basis. But still Cochran still has a valid point about the strange unaccounted for female infertility per individual in humans because so many women whom want to get pregnant never can or have a very difficult time.

        Hat tip to Cochran for naming this unknown but suspected group of archaic africans the Mangani. It’ll be a cold day in hell before science follows Cochran and gives this group this name offically. Tarzan books, which is where this name comes from aren’t exactly politicaly correct but those books along with the Conan series are just too campy and fun and science too dry and serious.

      • cloudswrest says:

        I wonder what it is per egg instead of per cycle. Most other animals have litters, so if a dog (bitch) produces 16 eggs and has a success rate of 25%, that would be 4 pups per fertilization.

  2. Bobo says:

    Autism/Bipolar/Schizophrenia?
    They’re caused by overlapping genes and BPD was linked to Neanderthal ancestry in a recent paper (in Medical Hypothesis, mind you):

    “Given evidence of Neandertal contributions to the human genome, the hypothesis is extended (EOBD-R) to suggest Neandertal as the ancestral source for bipolar vulnerability genes (susceptibility alleles).”

    http://www.ncbi.nlm.nih.gov/pubmed/22036090

    • Ian says:

      Perhaps there is some link with Seasonal Affective Disorder, which has been hypothesised to have a hibernatory function. If so, you’d expect it to be more prevalent among people whose ancestors lived in northerly latitudes for a long time.

  3. JRM says:

    “Partly I wonder about this because of the anomalously low success rate of human fertilization. It’s very unusual and nobody yet has an any explanation. ”

    Poor diet. When humans eat a neolithic diet, it harms reproduction. When humans eat a paleolithic diet, they get pregnant easier. Anecdotally, crossfit gyms (where they encourage eating a paleo diet) frequently have pregnant members. Also anecdotally, robitussin is sometimes recommended to women to reduce cervical mucus to make it easier for the sperm to get through. Why not avoid mucus producing foods? Neolithic foods such as dairy, wheat and sugar are the most notorious for producing mucus.

    Other anecdotal evidence:
    http://paleohacks.com/questions/68491/getting-pregnant-while-paleo-time-it-took-paleo-vs-non-paleo#axzz23ieqBdlJ

  4. TWS says:

    How is it that there was no gene swapping with the mangani and those who left Africa? Seems weird, all of them must have been in Africa at the same time to begin with.

  5. potsandkettles@gmail.com says:

    Isn’t this the true Holy Grail?

    For a novel, imagine that the main character wanted people like himself to take over the world over a relatively small number of generations. He’d engineer non-identical embryos with key desired features in a place that would greatly increase their chances of being picked during normal fertilization. He’d make a lot of these little kids himself and have them raised through tutors, and he’d also secretly place the sperm in top-rated sperm banks throughout the world. Then he’d set up a system of trusts to encourage the financial and academic success of the children. Larry Ellison probably already has a team of private detectives, scientists and lawyers working on it. (Like the Boys from Brazil but bigger and a with a little less Hitler. Or like 1/2 the world being descended from Genghis Khan. Or Moonraker.)

    The biggest obstacles are figuring the technique out now, keeping it totally secret, and then stopping others from figuring it out. But that would be a job for the black-bag guys and government lobbyists he hires to stop anyone from developing this dangerous technology. Too bad Michael Crichton is dead; he could do it.

    At the end, we should learn that the main investigator is actually one of them. (Like Blade Runner.)

    • dave chamberlin says:

      You ask a fun interesting question but I propose a different answer. Science isn’t close to explaining why their is such variation in human intelligence but science is already successful in cloning. Take a repressive backwards country and give financial incentives to poor parents to become the foster parent to a child whom is the clone of an under age 40 (DNA starts to decline) recognized genius. Lets say only 1% of the population takes up the governments offer. What happens to that poor backwards country when 1% of their population grows up to be productive citizens that are in the upper 1% of 1% (one in ten thousand) of world intelligence. My best guess is that the results will be so positive that other countries follow suit.

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