Who does this?
|Testing Models of Human Origins and Archaic Admixture
A basic goal in anthropology is to discern the major evolutionary events and processes
that provide the historical framework for our species. Behavioral and morphological changes
together with their ecological and environmental contexts form the background for understanding
both the adaptive and neutral genetic changes that have produced contemporary patterns of human
biological variation. The goals of this collaborative project (with Jeff Wall at UCSF)
are to systematically survey neutral genetic variation at multiple loci in the nuclear
genome, and to develop novel statistical approaches for explicitly testing a number of
hypotheses pertaining to the manner in which the human genome and the human species evolved.
DNA sequence data were generated from >90 genomic regions in a sample of humans from geographically
diverse populations in sub-Saharan Africa, Eurasia, and Oceania, as well as representatives of the
great apes. Each locus was chosen from a genomic region with a moderate rate of recombination and
low density of genes to minimize the possible confounding effects of recent natural selection.
These data are being used to address the following questions:
Objective I: One of the most interesting unanswered questions about our origins is whether
anatomically modern humans (AMH) and archaic forms interbred after AMH expanded out of Africa.
The first objective of this proposal is to test the hypothesis of ancient admixture between
Homo sapiens and archaic forms such as H. neanderthalensis and H. erectus. We have developed
new methodology for testing the null hypothesis of no admixture and (if the null model is rejected)
estimating the amount of admixture. Our statistical framework also allows us to assess the degree
of uncertainty surrounding these admixture estimates.
Objective II: While the preponderance
of genetic data supports an African origin of AMH, a major unanswered question that has been largely
overlooked in African replacement models is whether H. sapiens evolved in the presence of significant
population structure in Africa. In other words, were our ancestors spread over a broad geographic
area within (and near) Africa during the transition to modern form? Statistical and computational
methods were developed for testing a number of hypotheses related to the history of population
subdivision during the transition to anatomically modern form. To do this we modified the admixture
model to incorporate geographic structure and developed new methods for estimating both the amount of
admixture and when geographic structure in AMH first arose. As before, the statistical framework will
let us determine how much confidence to place in the parameter estimates.
Despite recent advances in surveying DNA sequence variation in human populations, there is still no
consensus on the size or magnitude of a putative non-African bottleneck or when human populations
started their subsequent expansion. We are working to develop methods for estimating the timing and
strength of a non-African bottleneck and the timing of recent population growth. Both the total size
and geographic coverage of the data set (described in Objective I) coupled with the use of sophisticated
computational and statistical methodology will enable us to estimate growth and bottleneck parameters with
greater accuracy and precision than previous studies.
Cox, M.P., Mendez, F.L., Karafet, T.M., Pilkington, M.M., Kingan, S.B., Destro-Bisol, G., Strassmann, B.I., and Hammer, M.F. (2008). Testing for archaic hominin admixture on the X chromosome: model likelihoods for the modern human RRM2P4 region from summaries of genealogical topology under the structured coalescent. Genetics 178: 427-437.
Cox, M.P., Morales, D.A., Woerner, A.E., Sozanski, J., Wall, J.D., and Hammer, M.F. (2009). Autosomal resequence data reveal Late Stone Age signals of population expansion in sub-Saharan African foraging and farming populations. PLoS One 4: e6366.
Cox, M.P., Woerner, A.E., Wall, J.D., and Hammer, M.F. (2008). Intergenic DNA sequences from the human X chromosome reveal high rates of global gene flow. BMC Genet 9, 76.
Garrigan, D., and Hammer, M.F. (2006). Reconstructing human origins in the genomic era. Nat Rev Genet 7: 669-680.
Wall, J.D., Cox, M.P., Mendez, F.L., Woerner, A., Severson, T., and Hammer, M.F. (2008). A novel DNA sequence database for analyzing human demographic history. Genome Res 18: 1354-1361.
Wall, J.D., and Hammer, M.F. (2006). Archaic admixture in the human genome. Curr Opin Genet Dev 16: 606-610.
Woerner, A.E., Cox, M.P., and Hammer, M.F. (2007). Recombination-filtered genomic datasets by information maximization. Bioinformatics 23: 1851-1853.