The Loom

Natural selection can favor genes that allow children to grow up healthy. But in order to grow up healthy, they need nurturing from their mothers, both before and after birth. If a baby’s development puts a strain on a mother, she may end up having fewer children. That means she may spread fewer copies of her genes to later generations . That creates conditions in which natural selection may also genes that allow mothers to restrain their children. Our particular way of having kids puts genes in conflict.

I have an article in tomorrow’s New York Times on these conflicting genes, focusing on the visionary work of David Haig of Harvard University. As I explain in the article, Haig first wrote about his theory in the early 1990s. He made a number of predictions about pregnancy and fetal growth, many of which have only been tested in recent years. Many of them bolster his argument.

In articles such as this one, I usually have to struggle over which examples to include and which to leave out. Sometimes extemely cool ones demand a lot of explanation which would swamp the whole piece. In this case, I had to leave out a couple striking examples of how genes in conflict may create some of the most mysterious birth disorders around.

As I explain in the article, sometimes a mother’s or father’s copy of a gene is silenced. (This is sometimes called gene imprinting.) Haig argues that gene imprinting evolves to undercut the effect of genes from the other parent. A gene that stimulates growth in fetuses puts a strain on the mother. So the mother’s copy of the gene in the fetus is silenced, reducing the growth of the fetus. Imprinted genes are often linked to diseases, because only a single gene has to do a particular job, without backup from the other parent’s gene. And the effects of these disorders can reveal the evolutionary forces that drive the evolution of gene imprinting.

An estimated one in 25,000 babies is born with Prader-Willi syndrome, which causes them to show almost no interest in feeding. Prader-Willi syndrome has been linked to a set of imprinted genes. The syndrome may be triggered if a mutation deletes the father’s copies of these genes. So it may be that these are genes that drive the growth of babies by causing them to nurse more. Mothers hold the children back by silencing their copies of the genes.

By age three, children with Prader-Willi syndrome undergo a baffling change. They develop an insatiable appetite and an obsession with finding food. Prader-Willi can lead to severe obesity. Haig argues that this shift is also the result of genetic conflict. One clue is that it occurs right around the time when children are weaned. Weaning marks a major potential conflict for children and their parent. If a child can nurse longer, it may be more likley to thrive. But if a mother can wean her child, she doesn’t have to sacrifice more energy to make breast milk. Nursing also acts as a contraceptive, so putting a child onto solid food can make it possible for a mother to get pregnant again. The effects of Prader-Willi suggest that paternal genes are driving children to resist weaning. Mothers silence those genes to counteract that resistance.

Another enigmatic disorder is known as Angelman syndrome. Children with Angelman syndrome suffer from a number of symptoms, including retardation. But they’re most distinctive for abundant laughter and endless happiness. Angelman syndrome is caused by the disruption of imprinted genes. It’s the mother’s genes that are disrupted in Angelman syndrome, as opposed to the father’s in Prader-Willi.

What does it mean if disabling maternal genes causes children to laugh and be happy? In a paper in press, Lawrence Wilkinson and his colleagues at Cambridge University argue that babies use these sort of signals to get more attention from their mothers. So the genes that normally prevent Angelman syndrome may normally act as a brake on those signals.

These are speculations, but fascinating ones, and ones that line up with more thoroughly studied examples of genes in conflict. Fortunately, what can’t fit in the paper can always fit in the blog.

[Update 3/14: a little tinkering to clear up the beginning, per a commenter’s request]

Comments

  1. #1 luca
    March 14, 2006

    Carl, interesting article, but have to admit I’m quite confused by the timing of the first sindrome (Prader-Willi) you talk about: you says that the children’s behaviour is initially ‘disinterest’ in food, then at age three ossessive interest. soon after, you suggest that the conflict develops around weaning… are american children weaned at age of three?

  2. #2 Carl Zimmer
    March 14, 2006

    Luca–

    You can read the full Prader-Willi paper here: http://www.oeb.harvard.edu/faculty/haig/pdfs/03PraderWilli.pdf

    Anthropological data indicates children are weaned by their third birthday in foraging societies. The P-W increase in appepite kicks in around then.

  3. #3 Judith
    March 14, 2006

    Carl, this is a bit steep for some of us, so help me out, please. In the third sentence of the first paragraph there are one or two words missing which might help set me on the right path.

    signed
    The Niggler

  4. #4 Judith
    March 14, 2006

    Oops, it’s the fourth sentence. They’ll take my niggling badge away…

  5. #5 Saxa82
    March 14, 2006

    Mr. Zimmer,

    I read your NYT article, as well your your Loom post, with great interest. Some questions: When exactly does genomic imprinting happen- upon fertilization or later? Is this a random event, or are there factors that might predispose a gene to being turned off? And, of course, what is the evolutionary value of gene imprinting? Sorry for all the questions, this is a curious topic.

    Saxa82

  6. #6 luca
    March 15, 2006

    Thanks Carl,

    I’ll have a look at it…

    and my compliment for the site, I guess ‘Evolution’ will be pretty high in my Xmas wish list. for the time being, I’ll grab Parasite Rex – any relation with the parasite documentary series the BBC showed some years ago?

  7. #7 mj quinn
    March 16, 2006

    Genetic views of pre-eclampsia have been dented recently by epidemiological studies that suggest that the “change of partner” or “dangerous male” effect disappears with prolonged inter-pregnancy intervals. The Haig hypothesis is very interesting though there may be simple neurological mechanisms that connect intrauterine growth problems, maternal pre-eclampsia, and elevated cytokines (sFlt-1). Injuries to nerve plexi at the endometrial-myometrial interface (through straining, surgery, prolonged pushing in labour) may cause unsuccessful or poor implantation resulting in some features of the spectrum of reproductive loss that we elaborate as miscarriage, pre-eclampsia, IUGR, placenta accreta. A neural loop between the uterus and the kidney may account for the (in)ability of the mother to divert her blood flow. Similar denervation and cytokine elevations have been noted recently in the three benign gynaecological pathologies of endometriosis, adenomyosis and fibroids also associated with neural injuries (a nerve re-grows when it is divided in a soup of cytokines, growth factors, etc – reinnervation causes pain or discomfort in response to light touch – allodynia)

    Reinnervation may account for much pelvic pain, endometriosis, menorrhagia and all the other Greek words with which we confuse ourselves and our patients as benign gynaecology. That first labours may cause much of gynaecology was first suggested in 1955 by Willard Allen and Howard Masters of Kansas. Allen became chairman in New York and a Nobel Laureate; Masters was the first half of Masters and Johnson. The denervation-reinnervation view is a development of their earlier work.

    The idea that much of what happens to a woman in her first labour, unleashes her pelvic nerves against her which may cause cycles of denervation and reinnervation for the rest of her life (labour-denervation, pelvic pain-reinnervation, hysterectomy-denervation, postmenopausal pain/prolapse-reinnervation) is uncomfortable for many except perhaps the woman herself – and the legal profession ?

  8. #8 Luis
    March 16, 2006

    Wow, very interesting. One thing is bugging me though…
    Carl: “As I explain in the article, Haig first wrote about his theory in the early 1990s.”
    Is it REALLY a theory? I mean, this IS a science blog, and you DO focus on evolution, so shouldn’t that say “hypothesis” instead of “theory”? This is the kind of thing that makes creationists so annoying with their “it’s just a theory” arguments.

    Yeah, I’m a nitpicker.

  9. #9 Anna, nurse
    March 27, 2006

    Nutrition is very important not only for babys but for mothers as well.
    http://www.ambustat.com

  10. #10 erika
    September 11, 2007

    hola soy de argentina mi sorina tiene el sindrome prader willi.Se lo dectaron al mes ahora tiene 3 aos.No tiene retraso neurologico, esta de talla, altura y peso normal, solo que le cuesta hablar.si existe algun tratamiento o avence cientificos escribame. desde ya muchas gracias

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