Exceptional LINE density at V1R loci: the Lyon repeat hypothesis revisited on autosomes.

The mammalian olfactory system utilizes three large receptor families: the olfactory receptors (ORs) of the main nose and the vomeronasal type-1 and type-2 receptor genes (V1Rs and V2Rs) of the vomeronasal organ. We find that these loci are among the most long interspersed nuclear element (LINE)-dense regions of mammalian genomes. We investigate two evolutionary models to account for this cohabitation. First, we investigate an adaptive selection model, in which LINEs have contributed to expansions of mouse V1R repertoires. We find that even evolutionarily stable V1R loci are exceptionally LINE-rich compared to other genome loci, including loci containing other large gene clusters. Also, a more detailed analysis of specific V1R duplications does not reveal LINE patterns predicted by common LINE-mediated duplication mechanisms. Next, we investigate neutral models, in which LINEs were tolerated by, but not advantageous for, surrounding V1R genes. We find that V1R loci are exceptionally LINE-rich compared to other regions of similar AT base composition, and that duplicated V1R gene blocks are generally depleted of LINE elements, suggesting that these loci did not become densely populated with LINEs simply as a consequence of targeted integration or passive multiplication along with the genes. Finally, we show that individual LINE repeats of a given age at V1R, V2R, and OR loci exhibit a significantly longer average length than at other autosomal loci, suggesting a reduced tendency for these LINEs to be disrupted. We speculate that LINEs at V1R, V2R, and OR loci might be selectively retained because they contribute to allelic regulation of these three gene families.

Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes.

The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system.