Originally published as Genetics Published Articles Ahead of Print on August 20, 2008.

Genetics, Vol. 180, 367-379, September 2008, Copyright © 2008
doi:10.1534/genetics.108.088732

Effects of Spatially Varying Selection on Nucleotide Diversity and Linkage Disequilibrium: Insights From Deer Mouse Globin Genes

Jay F. Storz*,1 and John K. Kelly{dagger}

* School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588 and {dagger} Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, Kansas 66045

1 Corresponding author: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588.
E-mail: jstorz2{at}unl.edu

An important goal of population genetics is to elucidate the effects of natural selection on patterns of DNA sequence variation. Here we report results of a study to assess the joint effects of selection, recombination, and gene flow in shaping patterns of nucleotide variation at genes involved in local adaptation. We first describe a new summary statistic, Zg, that measures the between-sample component of linkage disequilibrium (LD). We then report results of a multilocus survey of nucleotide diversity and LD between high- and low-altitude populations of deer mice, Peromyscus maniculatus. The multilocus survey included two closely linked {alpha}-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to different elevational zones. The primary goals were to assess whether the {alpha}-globin genes exhibit the hallmarks of spatially varying selection that are predicted by theory (i.e., sharply defined peaks in the between-population components of nucleotide diversity and LD) and to assess whether peaks in diversity and LD may be useful for identifying specific sites that distinguish selectively maintained alleles. Consistent with theoretical expectations, HBA-T1 and HBA-T2 were characterized by highly elevated levels of diversity between populations and between allele classes. Simulation and empirical results indicate that sliding-window analyses of Zg between allele classes may provide an effective means of pinpointing causal substitutions.