Gene Expression

Another story about recent human evolution, this time, really recent. The paper in PLOS is A Drastic Reduction in the Life Span of Cystatin C L68Q Carriers Due to Life-Style Changes during the Last Two Centuries. A mouthful, but the authors are really good at explaining what they’re finding and why it’s important:

….The detrimental phenotypic impact of the L68Q mutation appears to have emerged in reaction to common life-style changes almost three centuries after the mutation occurred. We believe that this is the first report of phenotypic flexibility of a monogenic disease in reaction to life-style changes that fall within the normal range of behavior of a single population in the space of a few generations. Our results underline how single gene disorders with simple Mendelian inheritance can be affected by environmental factors, resulting in changed disease status.

It seems what happened is that when this mutation arose, on the order of 500 years ago in Iceland, its fitness implication was neutral. So one assumes that this gene spread via the standard dynamics of neutral evolution, possibly aided by small effective populations and inbreeding in pre-modern Iceland. The neutral theory of molecular evolution predicts that a great deal of extant polymorphism will be due to these sort of random walk forces as fitness irrelevant mutants constantly emerge, go extinct, or on rare occasions substitute for the ancestral variant at a locus.

Before 1800 the mutants for this gene had about the same lifespan as wild types. Though most neutral mutants go extinct there are enough mutations in the genetic background that a fair number will “float” up to appreciable frequencies. That seems to be what happened here. But then something changed…fitness does not exist in a vacuum, and the exogenous environmental parameters totally distorted the adaptive landscape. Instead of a case where the mutant and wild type were facing off on a flat surface the former now looked up to the latter on its fitness people. The population began to purify the gene pool of the now deleterious mutant through negative selection.

This shouldn’t be surprising. Many of the “diseases” of the modern world seem likely to have originally been less than lethal, perhaps even beneficial. Sickle cell is the most prominent case of a trait that was beneficial in one environment (malarial) being not so much in another (non-malarial). So with this simple environmental shift the mutant variant begins to be subjected to negative selection instead of persisting at an equilibrium frequency because of balancing dynamics (heterozygote advantage).

One possible implication of these sorts of dynamics is that the greater the rate of environmental change the more “flipping” of the signs of selection coefficients there will be for any given allele. 10,000 years ago most of humanity started making the shift toward an agrarian lifestyles, and I suspect that might have resulted in various adaptations. Within the past few centuries humanity has begun to transition away from the agrarian past into a urban future, and that might mean that we live in a time of great evolutionary change.

Related: ScienceDaily summary….


  1. #1 John Emerson
    June 27, 2008

    Lot of feminist-co-author-dottirs there, Razib.

  2. #2 windy
    June 27, 2008

    Lot of feminist-co-author-dottirs there

    Not necessarily more feminist than the average female Icelander…

    Very cool results, I think most people would assume that the effect of the modern environment would always be in the direction of less “hard selection”, but I doubt this is the only instance of the opposite.

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