The Biology of Genomes

Cold Spring Harbor Laboratory, New York, U. S.

May 12, 2006

228

Poster presentation

Rapid diversification of genes by frameshift translation

Kohji Okamura1,2, Lars Feuk1,2, Tomàs Marquès-Bonet3, Arcadi Navarro3, and Stephen W. Scherer1,2 1The Centre for Applied Genomics, Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, 2Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada, 3Unitat de Biologia Evolutiva, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

Gene and genome duplication, followed by divergence, contributes to organismal evolution. Exon shuffling, lateral gene transfer, gene fusion, and alternative splicing are mechanisms responsible for novel gene functions, but they generate homologous domains and do not usually lead to drastic innovation. Major novelties in genes can be introduced by frameshift mutations and here we identify 470 and 108 frameshift events that originate new gene segments in human and mouse, respectively. No exact interspecies overlap was observed suggesting high rates of acquisition of evolutionary events by frameshift translation. This inference is supported by a deficiency of TpA dinucleotide in the coding sequences, which decreases the occurrence of termination codons in frameshifted translations even on the complementary strand. It is also supported through observation of increased usage of the TGA codon as the termination signal in newer genes. These suggest that tolerated frameshift changes are a prevalent mechanism for the rapid emergence of new genes contributing to genome complexity and that protein-coding sequences are derived from existing or ancestral exons rather than form exonization of other sequences.