Primate evolution of an olfactory receptor cluster: Diversification by gene conversion and recent emergence of pseudogenes

The olfactory receptor (OR) subgenome harbors the largest known gene family in mammals, disposed in clusters on numerous chromosomes. We have carried out a comparative evolutionary analysis of the best characterized genomic O R gene cluster, on human chromosome 17p13. Fifteen orthologs from chimpanze e (localized to chromosome 19p15), as well as key OR counterparts from othe r primates, have been identified and sequenced. Comparison among orthologs and paralogs revealed a multiplicity of gene conversion events, which occur red exclusively within OR subfamilies. These appear to lead to segment shuf fling in the odorant binding site, an evolutionary process reminiscent of s omatic combinatorial diversification in the immune system We also demonstra te that the functional mammalian OR repertoire has undergone a rapid declin e in the past 10 million years: while for the common ancestor of all great apes an intact OR cluster is inferred, in present-day humans and great apes the cluster includes nearly 40% pseudogenes. (C) 1999 Academic Press.