Recent duplication, evolution and assembly of the human genome

摘要

It has been estimated that 5% of the human genome consists of interspersed duplicated material that has arisen over the last 30 million years of evolution. Two categories of recent duplicated segments can be distinguished: segmental duplications between non-homologous chromosomes (transchromosomal duplications) and duplications largely restricted to a particular chromosome (chromosome-specific duplications). A large proportion of these duplications exhibit an extraordinarily high degree of sequence identity at the nucleotide level (95%) spanning large (1--100 kb) genomic distances. Through processes of paralogous recombination, these same regions are targets for rapid evolutionary turnover among the genomes of closely related primates. The dynamic nature of these regions in terms of recurrent chromosomal structural rearrangement and their ability to create fusion genes from juxtaposed cassettes suggests that duplicative transposition has been an important force in the evolution of our genome.Cycles of segmental duplication over periods of evolutionary time may provide the underlying mechanism for domain accretion and the increased modular complexity of the vertebrate proteome. Further, our data suggest that a small fraction of important human genes may have emerged recently through duplication processes and will not possess definitive orthologues in the genomes of model organisms. I will discuss computational methods developed in my laboratory to 1) unambiguously identify recent genomic duplicates within the human genome and 2) to assess their importance in hominoid gene innovation. The impact of this chromosomal architecture for assembly of the final draft sequence will be discussed.