"Reverse ecology" and the power of population genomics

Abstract

Rapid and inexpensive sequencing technologies are making it possible to collect whole genome sequence data on multiple individuals from a population. This type of data can be used to quickly identify genes that control important ecological and evolutionary phenotypes by finding the targets of adaptive natural selection, and we therefore refer to such approaches as "reverse ecology." To quantify the power gained in detecting positive selection using population genomic data, we compare three statistical methods for identifying targets of selection: the McDonald-Kreitman test, the mkprf method, and a likelihood implementation for detecting d(N)/d(S) > 1. Because the first two methods use polymorphism data we expect them to have more power to detect selection. However, when applied to population genomic datasets from human, fly, and yeast, the tests using polymorphism data were actually weaker in two of the three datasets. We explore reasons why the simpler comparative method has identified more genes under selection, and suggest that the different methods may really be detecting different signals from the same sequence data. Finally, we find several statistical anomalies associated with the mkprf method, including an almost linear dependence between the number of positively selected genes identified and the prior distributions used. We conclude that interpreting the results produced by this method should be done with some caution.

Figure 1

Neutrality indices for all three datasets. Each point represents the neutrality index (NI) for a specific gene and the P-value associated with the McDonald-Kreitman test for that gene. For plotting purposes and so that each value for NI is defined, NI is calculated as (P_N+1/D_N+1)/(P_S+1/D_S+1). The lower line in each graph represents P=0.05 while the upper line represents P=0.05/n.

Figure 2

Effect of prior distribution on results from mkprf. Relationship between the standard deviation on the prior distribution chosen for γ and the number of genes found to be under positive selection using the non-hierarchical MCMC. The asterisk (*) indicates the value used in Bustamante et al. (2005). Note the different scales of the y-axis in each panel and the non-uniform values on the x-axis for all panels.