ASPM and mammalian brain evolution: a case study in the difficulty in making macroevolutionary inferences about gene-phenotype associations

摘要

Identifying the genetic basis of adaptive phenotypes can be a significant step towards understanding how that phenotype evolved. With the increased availability of interspecific molecular data, an approach to uncover such genes has been to search for signatures of adaptive evolution at the molecular level. Many analyses have adopted a candidate gene approach, focusing on genes with important developmental roles. One such candidate gene is ASPM, which is involved in neurogenesis and associated with major neurological disorders [1]. The molecular evolution of ASPM has been investigated for a decade (see electronic supplementary material, table S1), under the hypothesis that it contributes to primate brain evolution. A recent study by Xu et al. [2] extends the taxonomic scope by demonstrating that ASPM evolved adaptively in cetaceans. However, descriptive studies of patterns of selection are now being supplanted by those that explicitly test for gene-phenotype associations. Using such an approach, we find that Xu et al.'s conclusion that ASPM is linked to increases in cetacean encephalization quotient (EQ), a measure of relative brain size, is not supported. We highlight developments in the analysis of molecular data and phylogenetic methods that are capable of resolving major issues in functional gene-phenotype coevolution, which we hope will provoke discussion and aid future studies.