The primary objective of the proposed research is to study the origin of modern humans using patterns of DNA sequence variation at four genes experiencing low to high amounts of recombination on the X chromosome. Within the last ten years, studies of mitochondrial, Y chromosome, and autosomal genes have been used to make inferences about long-term effective population size, age of lineages, location of ancestral lineages, pattern and timing of major migrations, population expansions, admixtures, and bottlenecks, and the genetic affinities of different ethnic groups. However, recent studies in molecular population genetics have revealed that many genes in the genome are influenced by selection at linked sites and thus do not serve as useful markers for tracking population processes. Genes in regions of the genome experiencing the highest rates of recombination are likely to be the best candidates for evaluating several important parameters of interest in models of human origins, including coalescence time and effective population size.
The proposed research will explicitly evaluate a continuum of models from the Recent African Replacement model to the Multiregional Evolution model using data from the X chromosome. In particular, this research will (1) accurately estimate the time to the most recent common ancestor and the effective population size for individual geographic regions and for the human species as a whole, (2) reconstruct relationships of different geographic groups from patterns of genetic variation, and (3) provide a further test of the hypothesis that natural selection is acting to reduce genetic variability in genomic regions experiencing low rates of recombination. Variation will be assayed by sequencing non-coding DNA in each of two high-recombination genes and two low-recombination genes in a global sample of 40 humans and representatives of the great apes (Pan troglodytes and Pongo pygmaeus). For the two low-recombination genes, an additional 350 individuals representing many major ethnic groups will be surveyed using a mutation detection method (DHPLC) and DNA sequencing.
This proposal represents a collaborative effort that combines expertise in human evolution and population genetics. Global surveys of X chromosome variation will provide a critical framework for testing hypotheses on the origins of anatomically modern human populations and their subsequent dispersals throughout the world. The data generated in this research will also provide one of the most detailed pictures of the structure of genetic variation at the nucleotide level in a large worldwide sample and will help determine the relative importance of different forces (mutation, drift, selection, and recombination) in shaping patterns of DNA sequence variation in our species.
