Human mitochondrial, autosomal, and sex chromosomes exhibit relatively high levels of genetic diversity within sub-Saharan Africa, reflecting complex patterns of population history, migration, and subdivision and possibly the origin of modern humans within this region. The current challenge is to better characterize the genetic diversity within sub-Saharan Africa and to reconstruct the complex demographic history of the region. East Africa, in particular, is thought to be a likely source of a human migration out of Africa within the last 100,000 years. This region, however, remains highly under-sampled and under-represented in studies of genetic variation. Tanzania occupies a region of Africa which is linguistically, culturally, sociologically, and genetically complex. Populations speaking languages representing all four of the linguistic super-families present in Africa are located in close proximity to one another. In addition, these populations practice a variety of subsistence methods. Although they have been the focus of many ethnographic, linguistic, and archaeological studies, Tanzanian populations have been studied very little at the genetic level. The Hadzabe and Sandawe, two populations that currently practice (or in the recent past have practiced) a predominantly hunter-gatherer lifestyle, are linguistic isolates whose languages contain click consonants and have been a challenge to classify. Little is known about their relationship to one another, to neighboring peoples who speak distinct languages and practice different subsistence methods, or to southern African Khoisan-speaking peoples who also speak languages containing click consonants and are hypothesized to have originated in East Africa. The specific goals of this research project are to characterize genetic variation in the Hadzabe, Sandawe, and neighboring populations; to reconstruct the relationship of these East African populations to one another and to southern African Khoisan-speaking populations; and to test hypotheses regarding the possible origin of modern humans in East Africa. This proposed project is divided into three overlapping phases. Phase I includes the collection of blood and/or buccal cells from the Hadzabe, Sandawe and neighboring populations in central Tanzania. Phase II consists of DNA isolation and molecular typing of the samples collected in Phase I. Samples will be genotyped for markers on autosomes, X- and Y-chromosomes, and mtDNA analyzed both independently and as haplotypes. Phase III includes exploratory data analysis and hypothesis testing given the data generated in phase II. The data collected will be analyzed within the context of a broader African and global data set that currently exists and is expected to contribute both to the general knowledge of genetic diversity within sub-Saharan Africa and to the understanding of ancient and historical relationships among East African populations. In addition, because East Africa is the likely source of populations migrating out of Africa, these data will provide important new insights into the origin and evolution of modern humans in Africa and will make possible the testing of a wide range of hypotheses concerning the global spread of modern humans out of Africa.
