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Health

Jolie + Pitt = baby with low mutational load?

Gene ExpressionBy Razib KhanMay 21, 2006 2:30 PM

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There are reports coming out that Angelina Jolie is going into labor. This is improtant, because last year Armand Leroi spoke about the possible relationship between beauty and low mutational load. Leroi has posited that one way to decrease the effect of load is hybridization. The logic is simple: assume that each human carries multitudinous deleterious alleles, that is, nasty grams on particular genetic loci. If one assumes that these are predominantly recessive so that their negative implications really manifest themselves disproportionately when they are found in two copies, then mating between closely related individuals will increase the chance of two copies coming together because they're more likely to be shared. For example, to use an extreme case, imagine that a mother and a son "do the deed." If the mother carries 3 lethal alleles at 3 loci, the expectation is 1.5 for her son. But since genetics is discrete he'll have an integer value between 0 and 3, with 1 and 2 being more common (you can imagine it as a binomial distribution, E(X) = 1.5, Var(X) = 0.75). Now, at any given locus the mother can pass one of the lethals to her son, so.... at locus 1 there is a 0.5 chance of a lethal at locus 2 there is a 0.5 chance of a lethal at locus 3 there is a 0.5 chance of a lethal The chance that mother will contribute a lethal at any given locus in a mating is 0.5, so, at any given locus a mother X son mating would have a 0.5 X 0.5 change of lethality, or 0.25. So, at any locus there is a 0.75 chance of viability (non-lethality). But, each locus is independent, so multiplying across you get a 42% chance of viability. Not so hot. The same logic, to a far diminished level exists with cousins, and to a lesser extent with races (e.g., whites have a 1 out of 25 or so chance of being cystic fibrosis carriers, non-whites have a zero chance). Does this apply to interracial matings? I don't know, and I don't think anyone does. The a priori logic is clear, but as I said the risk of deleterious recessives can drop off rather quickly with increased genetic distance and one might encounter genetic incompatibilities once one starts to outbreed far enough. Which moves me to Jolie & Pitt. They are very beautiful people, with high levels of facial symmetry and well developed secondary sexual characteristics. Evolutionary psychologist Geoff Miller, and Leroi himself, have proposed that beauty is a marker for genetic fitness, and this genetic fitness is just a parameter which to a large extent reflects mutational load. In fact, Miller proposes that variance in mutational load between siblings is what allows our species to purge itself of deleterious alleles (the ugly unfit siblings don't reproduce, serving as a flusing system for the gene pool). Leroi's idea was that hybridization can mask deleterious alleles via dominance (that is, if two individuals are genetically dissimilar, then they presumably will not share many rare but very deleterious mutations across their loci). But, if you have individuals who are of low mutational load, voila, no need for gimmicks! There are 6 billion individuals in the world, it is possible that there are individuals with only a trifling mutational load compared to the human mean that walk amongst us. Note that though many very negative deleterious alleles are easily masked, heterozygosity is usually not perfect and mildly suboptimal. The human genome is large, and each locus is a crap shoot contingent upon the genetic conformation of one's parents. But imagine the possibilities if beautiful mutation free (relatively) parents come together to produce progeny, the variance in probabilities imply that some of their children might be even less mutationally loaded! (3 de novo mutations per generation seems trivial) In any case, I'll be looking at the baby pictures...that'll tell the tale if the child will be Leroi's 191 deleterious allele marvel (as opposed to the mean of 300).

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