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Positive Natural Selection in the Human Lineage

P. C. Sabeti, S. F. Schaffner, B. Fry, J. Lohmueller, P. Varilly, O. Shamovsky, A. Palma, T. S. Mikkelsen, D. Altshuler, and E. S. Lander
Science • 16 Jun 2006 • Vol 312, Issue 5780 • pp. 1614-1620 • DOI: 10.1126/science.1124309
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Abstract

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of natural selection in humans has largely been restricted to comparing individual candidate genes to theoretical expectations. The advent of genome-wide sequence and polymorphism data brings fundamental new tools to the study of natural selection. It is now possible to identify new candidates for selection and to reevaluate previous claims by comparison with empirical distributions of DNA sequence variation across the human genome and among populations. The flood of data and analytical methods, however, raises many new challenges. Here, we review approaches to detect positive natural selection, describe results from recent analyses of genome-wide data, and discuss the prospects and challenges ahead as we expand our understanding of the role of natural selection in shaping the human genome.
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These authors contributed equally to this work.

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P.C.S. is funded by the Damon Runyon Cancer Fellowship and the L'Oreal for Women in Science Award. We thank C. Bustamante, R. Nielsen, J. Akey, Y. Gilad, and C. Carlson for providing information from their previous publications. We also thank F. Steele, D. Reich, D. Hartl, R. Neilsen, D. Richter, C. Langley, M. Przeworski, A. Clark, J. Fay, S. Myers, T. Farhadian, T. Herrington, A. Foster, P. Sabeti, and four anonymous referees for careful review of our manuscript.

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Volume 312 • Issue 5780 • 16 June 2006
Pages: 1614 - 1620

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P. C. Sabeti*
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.
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S. F. Schaffner†,*
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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B. Fry
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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J. Lohmueller
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brown University, Providence, RI, USA.
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P. Varilly
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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O. Shamovsky
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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A. Palma
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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T. S. Mikkelsen
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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D. Altshuler
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Departments of Genetics and Medicine, Harvard Medical School, Boston, MA, USA.
Department of Molecular Biology, Center for Human Genetic Research, and Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
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E. S. Lander
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biology, MIT, Cambridge, MA, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
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Notes

† To whom correspondence should be addressed. E-mail: [email protected]

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