Dissertation Research: Tempo and Mode of HLA Evolution in the Americas

Arizona State University, Scottsdale AZ

Investigators

Abstract

The introduction of European infectious diseases to the Americas resulted in a catastrophic loss of life among the indigenous populations. While this tragedy was widespread throughout the Americas, it can be exemplified by the history of the Havasupai, a Yuman-speaking tribe of northern Arizona. The Havasupai inhabit a remote side canyon of the Grand Canyon and live in relative isolation. Between 1897 and 1905, the Havasupai suffered serial epidemics of introduced influenza and measles; only one-quarter of the population survived. Previous research suggests that these epidemics resulted in selection for individuals who were heterozygous at two major histocompatibility complex (MHC) genes, which are critical components of immunological defense against pathogens. To determine whether the pattern of variation at MHC genes in the Havasupai is the result of selection for pathogen resistance, we intend to perform a genome-wide survey of microsatellite loci, which are highly mutable markers that are not subject to natural selection. Because these markers are not subject to selection, their pattern of variation will reflect only the demographic history of the Havasupai. We will examine 106 loci spread over all 22 autosomes, three of which are linked to the MHC genes and 15 pairs are linked to one another. The patterns of inheritance, population variation, and association between linked pairs will determine conclusively if natural selection is responsible for the variation observed at the MHC genes of this representative population. This research promises to yield insight into the genetic consequences of the Native American population declines associated with colonization of the Americas by Europeans.