Genomics of olfaction in mammals
by Zhang, Xiaohong, Ph.D., COLUMBIA UNIVERSITY, 2009, 181 pages; 3373586

Abstract:

In many species, the sense of smell plays an important role in locating food, detecting predators or other dangers, navigating and communicating social information. Olfaction also plays important roles within the communication social information, impacting mate choice, mother-infant recognition, and signaling between members of a group. Traditionally, these two realms were though to be served by two different and largely separate olfactory subsystems; olfactory receptors (ORs) of the olfactory epithelium (OE) were thought to respond to environmental odors while vomeronasal receptors (VRs) of the vomeronasal organ (VNO) were the so-call “pheromone receptors”. Altogether, the molecular receptors in mouse underlying the sense of smell compromise an exceedingly large family with about 1000 ORs and about 300 VRs (∼200 V1Rs and ∼100 V2Rs). From the publicly available rat and mouse genomes, we extracted the complete OR and V1R repertoire, and performed a comprehensive comparative genomics analysis between these two types of receptors, both within and across these species. We found that V1Rs are indeed more species-specific than ORs; OR genes are more conserved with its orthologous counterparts in the other species, while V1Rs are more similar with their neighbors within the same species. Based on the sequences from this computational data mining, we designed two custom microarrays: one array containing all mouse receptors plus other genes of interest; the other array one containing all receptor genes for rat, dog, chimpanzee and human. Using these microarrays, we characterized the expression profile for mouse OR and VR genes in different tissues, at varying developmental ages, and certain transgenic mice. The temporal expression of OR and VR genes could be classified into different patterns, indicative of their behavioral functions. By applying samples from other species, such as rat, chimpanzee and human to our custom array, we were able to verify specific expression of ORs in OE and VR expression in VNO. Through these experiments, the poly(A) sites for all OR and VR genes were determined and 3'UTR sequences for about 2,500 receptor genes in mouse and rat were identified for the first time. A series of sequence analyses uncovered the existence of known regulatory functional elements as well as novel motifs. The custom arrays proved to be an excellent tool for this fundamental research on olfactory receptor regulation. Overall, my research characterized the genomics of ORs and VRs in depth and opened the door for future regulation research.

 
AdviserStuart Firestein
SchoolCOLUMBIA UNIVERSITY
SourceDAI/B 70-08, p. , Oct 2009
Source TypeDissertation
SubjectsNeurosciences; Bioinformatics
Publication Number3373586
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