Being Positive about Selection

H ow has language developed in humans and what genetic changes underlie our unique cognitive abilities? Accounts of positive selection that lead to such abilities in humans fascinate us because of the insight they provide into our own evolution, and into the many genetic differences that distinguish us from other apes. The genes that became fi xed in our lineage as a result of positive selection are, after all, the ones that make us human. But understanding which gene, or what proportion of a genome, is being driven to fi xation by natural selection is of more fundamental biological importance because it can tell us about speciation and the very nature of adaptation. Relatively recent advances in genomic sequencing and analysis tools have resulted in an explosion of papers on this topic. And as editors of a journal aiming to publish major advances in a fi eld, we face the challenge of identifying standards of excellence in the face of this increasing interest. But the papers vary across many dimensions: they are based on different types of data in a variety of systems and taxa, they use increasingly sophisticated methods, and they address different questions—from targeting disease to understanding the nature of selection and reproductive isolation. Recognizing an advance in this rapidly changing fi eld, where the quality and availability of data also differ substantially, is like trying to catch a moving target. Most genomic regions are thought to be evolving neutrally; that is, they accumulate mutations (by random genetic drift) that do not infl uence the fi tness of the organism. The traditional measure of whether a protein-coding gene deviates from this and is under positive selection is the relative rate at which nonsynonymous (amino acid– changing) and synonymous (silent) mutations are fi xed in a population [1,2]—the K a /K s ratio. If the latter is greater than the former (i.e., K a /K s >1), the assumption is that the gene is changing at a rate faster than would be expected under the neutral theory, and is therefore subject to Darwinian selection. Such a test on whole proteins, however, detects selection in only the more extreme cases. Recently, more powerful methods have focused on detecting selection at the level of individual codons (e.g., [3]), and there are established computer programs, such as PAML [4], that can be used to compare the same gene— codon by codon—in multiple …