The Olfactory System: Studies in Gene Regulation and Genome Evolution.

Experimental approaches:

Bioinformatics (comparative genomics, computation)
Molecular biology (RNA/DNA isolation/cloning/characterization)
Genetics (transfection, transgenics)
Cell Biology (neuronal cell culturing)

The olfactory system

The olfactory system is a primal sensory system for most animals. The sense of smell is required in order for animals to detect food sources, avoid predators, and find mates. To accomplish this, the olfactory system must distinguish among thousands of odorants in the environment. Moreover, the olfactory system must be specialized for the niche and lifestyle of each species. Our laboratory is concerned with these two fundamental issues: How does the olfactory system distinguish odorants, and how does the olfactory system evolve individual species capabilities?

Odorant receptor regulation underlies the ability to distinguish odorants

The ability to detect and distinguish among thousands of environmental odorants is based on a combinatorial recognition system. Encoded in the animal’s genome are about a thousand odorant receptor (OR) proteins that are expressed in olfactory sensory neurons. A specific “smell” is coded in the brain by a specific combination of receptor proteins that get stimulated by the unique combination of odorant chemicals elicited by that smell. The smell of “lemons”, for example, would result from a specific combination of OR proteins that become stimulated upon binding the specific set of inhaled chemicals emitted from a lemon. But, how does the brain know which specific set of OR proteins are active? The key to this ability is an critical organizing principle in the olfactory system: each sensory neuron transcribes only one OR protein, thus, each olfactory sensory neuron is dedicated to report the response of a single OR. The problem of how smells are recognized and interpreted by the animal can be reduced to the question of how sensory neurons develop their OR-specific phenotypes. A major part of the research in our laboratory is focused on this remarkable gene regulatory problem: what are the molecular mechanisms underlying a sensory neuron’s ability to exclusively express a single OR protein. We are using molecular biology, genetics, comparative genomics, and bioinformatic techniques to investigate gene regulation in the olfactory system.

Evolution of receptor repertoires contributes to species-specific olfaction

If different animals, even closely-related ones, possess an olfactory system adapted to their own unique niche and lifestyle, then there are two (not mutually exclusive) possibilities: either the repertoires of odorant receptor genes are species-specific (i.e., there are differences in peripheral responsiveness), or the post-synaptic wiring patterns are species-specific (i.e., there are differences in how the same combinations of odorants are responded to centrally). We have focused our attention on the former possibility, and in particular, on the evolution of candidate pheromone receptor gene repertoires in various species. Pheromones are chemicals emitted by members of one’s own species that elicit stereotyped reproductive/social responses. Most mammals have a “second nose”, the vomeronasal organ (VNO), whose functions have been tightly associated with mating and social behaviors. One family of odorant receptor proteins (therefore, candidate pheromone receptor proteins) expressed in the VNO is the V1R gene family. Since mating and social behaviors are often exquisitely species-specific, we speculate that the putative pheromone receptors of the VNO (e.g., V1Rs) will represent an extreme in species-specific adaptation. With this in mind, a second major aspect of our research is applying tools of molecular biology, comparative genomics, and bioinformatics to investigate how V1R repertoires become different during speciation.

Recent Publications

Pathak, Nidhi, Johnson, Paul, Getman, Mike and Lane, Robert P. (2009) Odorant receptor (OR) gene choice is biased and non-clonal in two olfactory placode cell lines, and OR RNA is nuclear prior to diffentiation of these lines, Journal of Neurochemistry, Volume 108, Number 2, January 2009, pp486-497(12).

Kurzweil, V., Getman, M., NISC Comparative Sequencing Program, Green, E., and Lane, R. P. (2009) Synmic evolution of V1R putative pheromone receptors between Mus musculus an Mus spretus. BMC Genomics 10:74.
  
Kambere, M-J., and Lane, R. P.  (2009) Exceptional LINE Desnity at V1R Loci: The Lyon Repeat Hypothesis Revisited on Autosomes. J. Mol. Evol, January 20, 2009.

Lane, R. P., Smutzer, G. S., and Doty, R. L. (2008). The Sense of Smell. In: Neurobiology, From Molecular Basis to Disease. R.A. Meyers, Ed. Volume 1. Weinheim: Wiley-VCH Verlag, pp. 163-232 [republished in second textbook].

Stewart, R. and Lane, R. P. (2007). V1R promoters are well conserved and exhibit common putative regulatory motifs. BMC Genomics. 8: 253.
 
Kambere, M-J., and Lane, R. P. (2007). Co-regulation of large and rapidly evolving repertoires of odorant receptor genes. BMC Neurosci. 8 (Suppl 3): S2.

Lane, R. P., Smutzer, G. S., and Doty, R. L. (2005). The Sense of Smell. In: Encyclopedia of Molecular Cell Biology and Molecular Medicine. R.A. Meyers, Ed. Volume 12. Second Edition. Wiley: 2005, pp. 637-705.

Young, J., Kambere, M.-J., Trask, B. J., and Lane, R. P. (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, R. P., Young J., Newman T., and Trask B. (2004). Species specificity in rodent pheromone receptor repertoires. Genome Res. 14: 603-608.
 
Young J. M., Shykind B. M., Lane R. P., Tonnes-Priddy L., Ross J. A., Walker M., Williams E. M., and Trask B. J. (2003). Odorant receptor expressed sequence tags demonstrate olfactory expression of over 400 genes, extensive alternate splicing and unequal expression levels. Genome Biol. 4, R71.

Lane, R. P., Roach J., Lee, I., Boysen C., Smit A., Trask B. J., and Hood L (2002).  Genomic analysis of the olfactory receptor region of the mouse and human T-cell receptor alpha/delta loci.  Genome Research 12, 81-87
 
Lane, R. P., Cutforth T., Friedman C., Axel R., Trask B. J., and Hood L (2002).  Genomic analysis of the murine chromosome-6 vomeronasal receptor gene cluster reveals common promoter motifs and a history of local duplication. Proc Natl Acad Sci U.S.A. 99, 291-296
  
Lane, R. P., Cutforth T., Young J., Athanasiou M., Friedman C., Rowen L., Evans G., Axel R., Hood L., and Trask B. J (2001).  Genomic analysis of orthologous mouse and human olfactory receptor loci.  Proc Natl Acad Sci U.S.A. 98, 7390-7395.
 
Fitzli, D., Stoeckli E. T., Kunz S., Siribour K., Rader C., Kunz B., Kozlov S. V., Buchstaller, A., Lane R. P., Suter D. M., Dreyer W. J., and Sonderegger P. (2000).  A direct interaction of axonin-1 with NgCAM-related cell adhesion molecule (NrCAM) results in guidance, but not growth of commissural axons.  J. Cell Biol.  149, 951-968.
 
Rowen L., Wong G. K., Lane R. P., and Hood L. (2000)   Intellectual property.  Publication rights in the era of open data release policies.  Science 289, 1881.
 
Vielmetter, J., X-N Cheng, K. Yamakawa, F. Miskevich, R. P. Lane, J. Korenberg, and W. J. Dreyer (1997).  Molecular characterization of human neogenin, a DCC-related protein, and mapping of its gene to chromosomal position 15q22.3-q23.  Genomics 41, 414-421.

Lane, R. P., X-N Cheng, K. Yamakawa, J. Vielmetter, J. Korenberg, and W. J. Dreyer (1996).  Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31.  Genomics 35, 456-465.