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Extending Genome-Wide Association Study Results to Test Classic Anthropological Hypotheses: Human Third Molar Agenesis and the “Probable Mutation Effect”
A genome-wide association study (GWAS) identifies regions of the genome that likely affect the variable state of a phenotype of interest. These regions can then be studied with population genetic methods to make inferences about the evolutionary history of the trait. There are increasing opportunities to use GWAS results—even from clinically motivated studies—for tests of classic anthropological hypotheses. One such example, presented here as a case study for this approach, involves tooth development variation related to dental crowding. Specifically, more than 10% of humans fail to develop one or more permanent third molars (M3 agenesis). M3 presence/absence variation within human populations has a significant genetic component (heritability estimate h2 = 0.47). The evolutionary significance of M3 agenesis has a long history of anthropological speculation. First, the modern frequency of M3 agenesis could reflect a relaxation of selection pressure to retain larger and more teeth following the origins of cooking and other food-softening behaviors (i.e., the genetic drift hypothesis or, classically, the “probable mutation effect”). Alternatively, commensurate with increasing hominin brain size and facial shortening, M3 agenesis may have conferred an adaptive fitness advantage if it reduced the risk of M3 impaction and potential health complications (i.e., the positive selection hypothesis). A recent GWAS identified 70 genetic loci that may play a role in human M3 presence/absence variation. To begin evaluating the contrasting evolutionary scenarios for M3 agenesis, we used the integrated haplotype score (iHS) statistic to test whether those 70 genetic regions are enriched for genomic signatures of recent positive selection. None of our findings are inconsistent with the null hypothesis of genetic drift to explain the high prevalence of human M3 agenesis. This result might suggest that M3 impaction rates for modern humans do not accurately retrodict those of the preagricultural past. Alternatively, the absence of support for the positive selection hypothesis could reflect a lack of power; this analysis should be repeated following the completion of more comprehensive GWAS analyses for human M3 agenesis.
Journal Article
Eating mud crabs in Kandahar
These sometimes harrowing, frequently funny, and always riveting stories about food and eating under extreme conditions feature the diverse voices of journalists who have reported from dangerous conflict zones around the world during the past twenty years. A profile of the former chef to Kim Jong Il of North Korea describes Kim's exacting standards for gourmet fare, which he gorges himself on while his country starves. A journalist becomes part of the inner circle of an IRA cell thanks to his drinking buddies. And a young, inexperienced female journalist shares mud crab in a foxhole with an equally young Hamid Karzai. Along with tales of deprivation and repression are stories of generosity and pleasure, sometimes overlapping. This memorable collection, introduced and edited by Matt McAllester, is seasoned by tragedy and violence, spiced with humor and good will, and fortified, in McAllester's words, with \"a little more humanity than we can usually slip into our newspapers and magazine stories.\"
eBook
