pixy: Unbiased estimation of nucleotide diversity and divergence in the presence of missing data

Abstract

AbstractPopulation genetic analyses often use summary statistics to describe patterns of genetic variation and provide insight into evolutionary processes. Among the most fundamental of these summary statistics areπanddXY, which are used to describe genetic diversity within and between populations, respectively. Here, we address a widespread issue inπanddXYcalculation: systematic bias generated by missing data of various types. Many popular methods for calculatingπanddXYoperate on data encoded in the Variant Call Format (VCF), which condenses genetic data by omitting invariant sites. When calculatingπanddXYusing a VCF, it is often implicitly assumed that missing genotypes (including those at sites not represented in the VCF) are homozygous for the reference allele. Here, we show how this assumption can result in substantial downward bias in estimates ofπanddXYthat is directly proportional to the amount of missing data. We discuss the pervasive nature and importance of this problem in population genetics, and introduce a user-friendly UNIX command line utility,pixy, that solves this problem via an algorithm that generates unbiased estimates ofπanddXYin the face of missing data. We comparepixyto existing methods using both simulated and empirical data, and show thatpixyalone produces unbiased estimates ofπanddXYregardless of the form or amount of missing data. In sum, our software solves a long-standing problem in applied population genetics and highlights the importance of properly accounting for missing data in population genetic analyses.