Unraveling ancient segmental duplication events in human genome by phylogenetic analysis of multigene families residing on HOX-cluster paralogons.

BACKGROUND Vertebrate genomes contain extensive intra-genomic conserved synteny, which is the presence of similar set of genes on two or more chromosomes (paralogons). The existence of these paralogons has led to the proposal that vertebrate genome was structured by one or more rounds of ancient whole genome duplications (2R hypothesis). RESULTS The 2R hypothesis was tested by phylogenetic analysis of gene families residing on human HOX-bearing chromosomes (HOX-cluster paralogons). These results revealed that, based on their duplication history, 23 gene families with representation on three or four of the human HOX-bearing chromosomes can be partitioned into four discrete co-duplicated groups. The distinct genes within each co-duplicated group share the same evolutionary history and are duplicated in concert with each other, while the constituent genes of two different co-duplicated groups do not share their evolutionary history and are not duplicated simultaneously. These co-duplicated groups are large constituting members from 3 to 8 gene families and suggest that human HOX-cluster paralogons were shaped by ancient segmental duplications (SDs) and rearrangement events that occurred at least as early as before the divergence of bony fishes and tetrapods. CONCLUSIONS Based on the recovery of ancient SD events in this analysis and given the widespread evidence in favor of the fact that recent SD events played a pivotal role in changing genome architecture of primates and other recently diverged animals, it is concluded that a more realistic model of ancient vertebrate genome evolutionary history can be deduced by tracing the evolutionary trajectory of the genomes of recently diverged vertebrate species.