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BACKGROUND:The field of ancient DNA has recently entered the genomics era, with several available whole nuclear genomes. Thus, it is now possible to address fundamental evolutionary questions utilizing ancient DNA, and there is particular interest in the possibility of further quantifying the tempo and mode of positive selection. However, there exist a paucity of methods for analyzing ancient DNA, and the uniquely valuable time-serial aspect of such data is often disregarded.AIMS:The goals of my proposal are to 1) develop methods tailored to the characteristics of ancient DNA, and 2) apply those methods to answer biologically relevant questions related to the adaptation to high altitude in the Andes and the domestication of modern horses. The proposed methods aim to detect regions of the genome under positive selection, and specifically to identify genomic regions underlying phenotypic adaptations particular to these two examples.METHODOLOGY:Methods:Building upon existing methodology based on diffusion approximation to classical population genetics models, our first aim will be to extend one-locus theory to whole genomes, taking a likelihood approach. The second and third extensions will involve the utilization of linkage information and a relaxation of the assumptions governing the strength of selection, respectively. Data:The developed methodology, though anticipated to be widely applicable across the field, will be highlighted in two illustrative applications herein:1)whole nuclear genomes from pre- and post-domesticated horses - allowing for the identification of regions important in the process of domestication2)sequenced exomes from 15 mummy samples from the Andes - in order to characterize the selective sweeps associated with adaptation to high altitude on the Altiplano.RELEVANCE:Our findings will have relevance in several related areas. The methods will benefit the ancient DNA community, but also fields such as experimental evolution and epidemiology where data is collected at several time points. In order to facilitate this exchange - all developed code and methodology will be hosted from the lab website, with extensive documentation. The biological applications will be of general importance as well, both to 1) understand how the domestication process is reflected in the genome of modern horse, but also to understand the genetics of artificial selection induced via domestication in general, and 2) will have applications to medicine given the similar physiological challenges at high altitude and those stresses generated by a heart or lung failure.