Large multi-chromosomal duplications encompass many members of the olfactory receptor gene family in the human genome

The human genome contains thousands of genes that encode a diverserepertoire of odorant receptors (ORs). We report here on the identificationand chromosomal localization of 74 OR-containing genomic clones. Usingfluorescence in situ hybridization (FISH), we demonstrate a strikinghomology among a set of approximately 20 OR locations, illustrating ahistory of duplications that have distributed OR sequences across thegenome. Half of the OR-containing BACs cloned from total genomic DNA and86% of cosmids derived from chromosome 3 cross- hybridize to a subset ofthese locations, many to 17 of them. These paralogous regions aredistributed on 13 chromosomes, and eight lie in terminal bands. Byanalyzing clones from an approximately 250 kb clone- walk across one ofthese sites (3p13), we show that the homology among these sites isextensive (>150 kb) and encompasses both OR genes and intergenic genomicsequences. The FISH signals appear significantly larger at some sites thanat the native location, indicating that portions of some duplicons haveundergone local amplification/attrition. More restricted duplicationsinvolving pairs of other genomic locations are detected with 12% of theOR-BACs. Only a small subset of OR locations is sufficiently diverged fromthe others that clones derived from them behave as single-copy FISH probes.We estimate that duplications encompassing members of the OR gene familyaccount for >0.1% of the human genome. A comparison of FISH signals atorthologous locations in other primates indicates that a portion of this OR'subgenome' has been in flux during the divergence of primates, possibly asa mechanism for evolving the repertoire of olfactory receptors.