Gene family phylogenetics: tracing protein evolution on trees

How have proteins taken on the remarkable diversity of biochemical and physiological functions necessary to create and maintain complex organisms? The majority of proteins are organized hierarchically into families and superfamilies, reflecting an ancient and continuing process of gene duplication and divergence. The techniques of molecular phylogenetics, developed to recover the nested hierarchy of taxa from character information in their gene sequences, can also reconstruct the evolutionary relationships among genes and provide a conceptual foundation for comparative evolutionary analysis of proteins and their functions. In this review, I outline the application of phylogenetic approaches to issues in gene family studies, beginning with the inference of phylogeny and the assessment of the two types of homology by which genes in a family can be related: orthology (common descent from a cladogenetic event) and paralogy (common descent from a gene duplication event). I show how the phylogenetic approach makes possible novel kinds of comparative analysis, including detection of exon shuffling, reconstruction of the evolutionary diversification of gene families, tracing of evolutionary change in protein function at the amino acid level, and prediction of structure-function relationships. A marriage of the principles of phylogenetic systematics with the copious sequence data being generated by molecular biology and genomics promises unprecedented insights into the nature of biological organization and the historical processes that created it.