Pheromonal communication is a critical mediator of reproductive and social behaviors. The ability to respond to pheromonal cues from individuals within the species, and to avoid being confused by pheromonal signals from other species, is clearly important. This raises interesting questions regarding the evolution of distinct pheromonal systems during speciation. This project utilizes a combination of molecular, genetic, and genomic approaches to investigate how rodent pheromonal systems have evolved in species-specific ways and how pheromone receptor genes are regulated to recognize and distinguish pheromones.
In Aim 1, we will investigate our hypothesis that repeat-mediated V1R duplication led to punctuate divergence in routine pheromone systems. These studies will indicate subsets of pheromone receptor genes that likely underlie the ability of species to communicate exclusively. More broadly, these studies should provide insights into the general role of repeat structures in the punctuated evolution of genomes.
In Aim 2, we will use bioinformatic approaches to identify putative regulatory sequences in V1R promoter regions. These studies will build on j previous work in which locus-specific and cross-locus putative regulatory features were identified. The specific hypothesis we are investigating is that V1R gene choice is hierarchical, involving selection of a genomic locus followed by selection of a single gene within the cluster.
In Aim 3, we will identify transcription factors that interact with putative regulatory sequences identified previously. Specifically, we will investigate the function of a locus-specific promoter motif identified near all V1R promoters in one cluster, as well as a motif within this cluster that is homologous to the globin Locus Control Region.
In Aim 4, we will test the hypothesis that VIR genes regulate by locus-based mechanisms, a hypothesis that is born from several genomic observations and is consistent with the punctuated expansion of specific loci during evolution. We will knock-in a V1R transgene to a non-native (and native) genomic position to investigate whether V1R genes regulate autonomously. More broadly, these studies may provide insights into how the genome is partitioned into regulatory compartments. The partnership between the Chess group, with considerable expertise in transgenics and olfactory biology, and the Lane group, with broad experience in bioinformatics and molecular evolution, represents an important niche that unites genomics and functional biology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC006267-01
Application #
6674380
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2003-07-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$382,509
Indirect Cost
Name
Wesleyan University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
145683954
City
Middletown
State
CT
Country
United States
Zip Code
06459
Vyas, Rutesh N; Meredith, Diane; Lane, Robert P (2017) Lysine-specific demethylase-1 (LSD1) depletion disrupts monogenic and monoallelic odorant receptor (OR) expression in an olfactory neuronal cell line. Mol Cell Neurosci 82:1-11
Kilinc, Seda; Savarino, Alyssa; Coleman, Julie H et al. (2016) Lysine-specific demethylase-1 (LSD1) is compartmentalized at nuclear chromocenters in early post-mitotic cells of the olfactory sensory neuronal lineage. Mol Cell Neurosci 74:58-70
Kilinc, Seda; Meredith, Diane T; Lane, Robert P (2014) Sequestration within nuclear chromocenters is not a requirement for silencing olfactory receptor transcription in a placode-derived cell line. Nucleus 5:318-30
Kurzweil, Vanessa C; Getman, Mike; NISC Comparative Sequencing Program et al. (2009) Dynamic evolution of V1R putative pheromone receptors between Mus musculus and Mus spretus. BMC Genomics 10:74
Pathak, Nidhi; Johnson, Paul; Getman, Michael et al. (2009) Odorant receptor (OR) gene choice is biased and non-clonal in two olfactory placode cell lines, and OR RNA is nuclear prior to differentiation of these lines. J Neurochem 108:486-97
Kambere, Marijo B; Lane, Robert P (2009) Exceptional LINE density at V1R loci: the Lyon repeat hypothesis revisited on autosomes. J Mol Evol 68:145-59
Kambere, Marijo B; Lane, Robert P (2007) Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes. BMC Neurosci 8 Suppl 3:S2
Stewart, Robert; Lane, Robert P (2007) V1R promoters are well conserved and exhibit common putative regulatory motifs. BMC Genomics 8:253
Young, Janet M; Kambere, Marijo; Trask, Barbara J et al. (2005) Divergent V1R repertoires in five species: Amplification in rodents, decimation in primates, and a surprisingly small repertoire in dogs. Genome Res 15:231-40
Lane, Robert P; Young, Janet; Newman, Tera et al. (2004) Species specificity in rodent pheromone receptor repertoires. Genome Res 14:603-8