Pattern and timing of gene duplication in animal genomes

Abstract

Duplication of genes, giving rise to multigene families, has been a characteristic feature of the evolution of eukaryotic genomes. In the case of vertebrates, it has been proposed that an increase in gene number resulted from two rounds of duplication of the entire genome by polyploidization (the 2R hypothesis). In the most extensive test to date of this hypothesis, we compared gene numbers in homologous families and conducted phylogenetic analyses of gene families with two to eight members in the complete genomes of Caenorhabditis elegans and Drosophila melanogaster and the available portion of the human genome. Although the human genome showed a higher proportion of recent gene duplications than the other animal genomes, the proportion of duplications after the deuterostome-protostome split was constant across families, with no peak of such duplications in four-member families, contrary to the expectation of the 2R hypothesis. A substantial majority (70.9%) of human four-member families and four-member clusters in larger families showed topologies inconsistent with two rounds of polyploidization in vertebrates.

Figure 1

(a) Phylogenetic tree showing the major cladogenetic events used in timing gene duplications: (A–F) the animal–fungus divergence; (C–N), the coelomate–nematode divergence; (D–P), the deuterostome–protostome divergence. The topology of the tree and the divergence time estimates (±SE) are from Wang et al. (1999). However, gene duplications were timed relative to cladogenetic events independent of a molecular clock assumption. (b) Hypothetical gene family containing two human members (A and B). If the internal branch (indicated by arrow) is significantly supported, we can conclude (independent of the rooting of the tree) that A and B diverged prior to the deuterostome–protostome divergence. (c) Hypothetical four-member human gene family having a topology of the form (AB) (CD) consistent with the hypothesis of two rounds of genome duplication (the 2R hypothesis). (d) Hypothetical four-member human gene family having a topology of the form (A) (BD) inconsistent with the 2R hypothesis.

Figure 2

Numbers of gene duplications in two- to eight-member families. A duplication was dated prior to one of the three a major cladogenetic events (the animal–fungus divergence, the coelomate–nematode divergence, and the deuterostome–protostome divergence) if its occurrence prior to the event was supported by a significant internal branch. Chi square tests of the hypothesis that the proportion of duplications prior to a cladogenetic event differed from that in Drosophila: (***) P < 0.001. Numbers of duplication events were as follows: Caenorhabditis elegans, 463; Drosophila 567; human, 1760.

Figure 3

Numbers of gene duplications in three family size classes (two- to three-member families, four-member families, five- to eight-member families). A duplication was dated prior to one of two major cladogenetic events, (a) the coelomate–nematode divergence, and (b) the deuterostome–protostome divergence, if its occurrence prior to the event was supported by a significant internal branch. Chi-square tests of the uniformity across family size classes of the proportion of duplications prior to the cladogenetic event : (**) P < 0.01; (***) P< 0.001.