Abstract
BackgroundEvolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations.ResultsWe sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47%) of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently.ConclusionOur demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of these genes is not? This phenomenon may be related to the nature of their ligands and their importance in everyday life.
Highlights
Evolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes
We determined the nucleotide sequences of PCR fragments amplified from DNA purified from a cohort of 48 dogs of six breeds: German Shepherd Dog (GSD), Belgian Malinois (BM), Labrador Retriever (LR), English Springer Spaniel (ESS), Greyhound (Grey) and Pekingese (Pek)
We have shown here that overall OR gene diversity is very high, with a mean distance (N) between SNP of 577 nt, slightly less than that calculated for non-coding sequences and much shorter than the distances calculated for exon sequences
Summary
Evolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. The conserved residues are thought to be involved in signal transduction, whereas the variable residues are thought to be involved in binding thousands of odorant molecules in specific interactions [7,9,10,11]. They were domesticated from wolves some 15,000 years ago and have since undergone extensive breeding and selection, resulting in 400 or so different breeds, some of which were developed for hunting, in which olfaction plays a central role [12,13,14,15]. As a case in point, links between nucleotide polymorphisms in two OR genes in humans (OR7D4 and OR11H7P) and the perception of specific odorants – androstenone and isovaleric acid, respectively – have recently been demonstrated [16,17,18]
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