Abstract

Comparative genome analyses reveal that most functional domains of human genes have homologs in widely divergent species. These shared functional domains, however, are differentially shuffled among evolutionary lineages to produce an increasing number of domain architectures. Combined with duplication and adaptive evolution, domain shuffling is responsible for the great phenotypic complexity of higher eukaryotes. Although the domain-shuffling hypothesis is generally accepted, determining the molecular mechanisms that lead to domain shuffling and novel gene creation has been challenging, as sequence features accompanying the formation of known genes have been obscured by accumulated mutations. The growing availability of genome sequences and EST databases allows us to study the characteristics of newly emerged genes. Here we review recent genome-wide DNA and EST analyses, and discuss the three major molecular mechanisms of gene formation: (1) atypical spicing, both within and between genes, followed by adaptation, (2) tandem and interspersed segmental duplications, and (3) retrotransposition events.