Gene family evolution and homology: Genomics meets phylogenetics

With the advent of high-throughput DNA sequencing and whole-genome analysis , it has become clear that the coding portions of the genome are organized hierarchically in gene families and superfamilies. Because the hierarchy of genes, like that of living organisms, reflects an ancient and continuing p rocess of gene duplication and divergence, many of the conceptual and analy tical tools used in phylogenetic systematics can and should be used in comp arative genomics. Phylogenetic principles and techniques for assessing homo logy, inferring relationships among genes, and reconstructing evolutionary events provide a powerful way to interpret the ever increasing body of sequ ence data. In this review, we outline the application of phylogenetic appro aches to comparative genomics, beginning with the inference of phylogeny an d the assessment of gene orthology and paralogy. We also show how the phylo genetic approach makes possible novel kinds of comparative analysis, includ ing detection of domain shuffling and lateral gene transfer, reconstruction of the evolutionary diversification of gene families, tracing of evolution ary change in protein function at the amino acid level, and prediction of s tructure-function relationships. A marriage of the principles of phylogenet ic systematics with the copious data generated by genomics promises unprece dented insights into the nature of biological organization and the historic al processes that created it.