Testing the hypothesis of genome duplications in vertebrates

Abstract

The hypothesis that the human genome has undergone at least two rounds of genome duplication has become widely accepted, but has never been rigorously tested. In this study, several map-based inter- and intra-species comparisons and simulations were used to critially examine this hypothesis. Interspecific map comparisons between human and mouse were thought to be the most likely to yield useful information. Discovery of conserved duplicated regions between human and mouse would allow the estimation of the date of divergence of the paralogous genes, and therefore also the date of the last genome duplication. But disappointingly, we observed very few such regions. Human-human intraspecies comparisons also yielded very little information. We demonstrated that most paralogous regions within the human genome, defined by genes separated by more than about 2 - 10 cm, are likely to be artefacts. It has also been shown that a simple model of evolution by two genome duplications (and no other duplication events) is likely to be misleading. A system of filtering output from TblastX to find more biologically significant matches by comparing the rates of synonymous versus non-synonymous rates of nucleotide substitution is presented.