The proposed research is intended to develop mathematical and statistical methods for analyzing DNA sequence data from individuals sampled from several closely related populations. One part of the proposed research will be to develop methods that allow inference of past and present patterns of migration and admixture. The methods will be applied to DNA sequences from individuals from several human populations and from extinct human relatives, including Neanderthals and Denisovans (a distant relative of Neanderthals). The proposed research is intended to provide improved ways of understanding the history of humans and their close relatives. One goal will be to characterize the admixture that occurred between humans, Neanderthals, Denisovans, and other extinct human relatives. A second goal will be to identify genes in the human genome that recently increased in frequency under the effect of natural selection since the separation from Neanderthals and Denisovans but before the divergence of modern human populations. Although these methods are motivated by the recently available genomes from Neanderthals and Denisovans, they will be applicable to other groups of closely related species as more genomic data becomes available. The second part of the proposed research will be to develop methods for using DNA sequence data from a single species to detect evidence of a recent expansion in geographic range either into an empty habitat or a habitat already containing a resident admixing species. The goal will be to determine whether a range expansion has taken place, where its geographic origin was, and to infer details of the expansion, including the effective number of founders at the leading edge. These methods will be applied to data from several human populations in order to understand the recent history of population movement.

Public Health Relevance

The proposed research is intended to develop mathematical and statistical methods for analyzing DNA sequence data from individuals sampled from several closely related populations and to apply of those methods to data from human populations and their extinct close relatives, Neanderthals and Denisovans. One goal of the proposed research is to reveal past patterns of migration, admixture and range expansion in humans and to characterize the history of interactions of humans with Neanderthals and Denisovans. A second goal is to identify regions of the human genome that have been favored by recent natural selection since the separation from Neanderthals and Denisovans.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM040282-26A1
Application #
8696418
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
1988-09-01
Project End
2018-02-28
Budget Start
2014-04-01
Budget End
2015-02-28
Support Year
26
Fiscal Year
2014
Total Cost
$281,057
Indirect Cost
$91,057
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Racimo, Fernando; Schraiber, Joshua G (2014) Approximation to the distribution of fitness effects across functional categories in human segregating polymorphisms. PLoS Genet 10:e1004697
Schraiber, Joshua G (2014) A path integral formulation of the Wright-Fisher process with genic selection. Theor Popul Biol 92:30-5
Fu, Qiaomei; Li, Heng; Moorjani, Priya et al. (2014) Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514:445-9
Lazaridis, Iosif; Patterson, Nick; Mittnik, Alissa et al. (2014) Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513:409-13
Macholdt, Enrico; Lede, Vera; Barbieri, Chiara et al. (2014) Tracing pastoralist migrations to southern Africa with lactase persistence alleles. Curr Biol 24:875-9
Prufer, Kay; Racimo, Fernando; Patterson, Nick et al. (2014) The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505:43-9
Slatkin, Montgomery (2013) A method for estimating the effective number of loci affecting a quantitative character. Theor Popul Biol 89:44-54
Landis, Michael J; Schraiber, Joshua G; Liang, Mason (2013) Phylogenetic analysis using Levy processes: finding jumps in the evolution of continuous traits. Syst Biol 62:193-204
Rohlfs, Rori V; Murphy, Erin; Song, Yun S et al. (2013) The influence of relatives on the efficiency and error rate of familial searching. PLoS One 8:e70495
Schraiber, Joshua G; Mostovoy, Yulia; Hsu, Tiffany Y et al. (2013) Inferring evolutionary histories of pathway regulation from transcriptional profiling data. PLoS Comput Biol 9:e1003255

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