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Genome Res. 15:1211-1221, 2005
©2005 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/05 $5.00
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Letter

Fitting background-selection predictions to levels of nucleotide variation and divergence along the human autosomes

Floyd A. Reed1,3,4, Joshua M. Akey2 and Charles F. Aquadro1

1 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA 2 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

The roles of positive directional selection (selective sweeps) and negative selection (background selection) in shaping the genome-wide distribution of genetic variation in humans remain largely unknown. Here, we optimize the parameter values of a model of the removal of deleterious mutations (background selection) to observed levels of human polymorphism, controlling for mutation rate heterogeneity by using interspecific divergence. A point of "best fit" was found between background-selection predictions and estimates of human effective population sizes, with reasonable parameter estimates whose uncertainty was assessed by bootstrapping. The results suggest that the purging of deleterious alleles has had some influence on shaping levels of human variation, although the effects may be subtle over the majority of the human genome. A significant relationship was found between background-selection predictions and measures of skew in the allele frequency distribution. The genome-wide action of selection (positive and/or negative) is required to explain this observation.

3 Present address: Department of Biology, University of Maryland, College Park, MD 20742, USA.

4 Corresponding author.
E-mail freed{at}umd.edu; fax (301) 314-9358.

[Supplemental material is available online at www.genome.org.]

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3413205.


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