Pheromones are chemicals emitted and sensed by conspecifics to elicit social and sexual responses and are perceived in terrestrial vertebrates primarily by the vomeronasal organ (VNO). Pheromone receptors in the mammalian VNO are encoded by the V1R and V2R gene superfamilies. The V1R superfamily contains 187 and 102 putatively functional genes in the mouse and rat, respectively. To investigate whether this large repertoire size is typical among mammals with functional VNOs, we here describe the V1R repertoires of dog, cow, and opossum based on their draft genome sequences. The dog and cow have only 8 and 32 intact V1R genes, respectively. Thus, the intact V1R repertoire size varies by at least 23-fold among placental mammals with functional VNOs. To our knowledge, this size ratio represents the greatest among-species variation in gene family size of all mammalian gene families. Phylogenetic analysis of placental V1R genes suggests multiple losses of ancestral genes in carnivores and artiodactyls and gains of many new genes by gene duplication in rodents, manifesting massive gene births and deaths. We also identify 49 intact opossum V1R genes and discover independent expansions of the repertoire in placentals and marsupials. We further show a concordance between the V1R repertoire size and the complexity of VNO morphology, suggesting that the latter could indicate the sophistication of pheromone communications within species. In sum, our results demonstrate tremendous diversity and rapid evolution of mammalian V1R gene inventories and caution the generalization of VNO biology from rodents to all mammals. evolution ͉ dog ͉ cow ͉ opossum ͉ rodents

Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the “less-is-more” hypothesis). However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the “less-is-more” hypothesis.