The human genome has about 400 olfactory receptor genes, while the elephant genome has over 1200. Does this mean elephants smell three times better than us? To discover what these differences mean requires reliable counts of the number of olfactory receptor repertoires in the genome.
As it turns out, this is not straightforward. Olfactory receptors are encoded by genes that evolve by gene duplication, whereby a single gene will replicate itself many times over and accumulate different changes over time, but will still retain a similar “olfactory receptor” motif. Because of this genetic mechanism, olfactory gene sequences are highly similar to one another and similar receptors tend to be next to each other in the genome. Similarity and redundancy make it challenging and expensive to sequence genes that evolve by gene duplication, but this is doubly so for olfactory receptors because they comprise the largest gene family in the mammal genome, including our own. Out today in Molecular Ecology Resources, Yohe, et al. (2019) have measured just how difficult sequencing olfactory receptors can be and found a cost-effective way to do so.
The study compared methods to sequence the olfactory receptors of the common vampire bat, a species that both consumes only blood from other mammals and relies on the sense of smell to find its prey. It was important to use the vampire bat for comparison because, while it relies on the sense of smell, it has roughly as many olfactory receptors as humans, making it tractable to study variation across methods. These different methods ranged from traditional PCR and cloning, to pioneering technology by designing specific probes to sequence bat olfactory receptors, referred to as “targeted sequence capture” (similar to “Find” for the genome).
Olfactory receptor genes recovered from each method compared to genome sequences. Each row indicates a single olfactory gene identified in the genome (red = present, white = not found).
The study found almost four times as many intact receptors as previously published, with some sequencing approaches vastly underestimating the number of olfactory receptors in the genome. Thus, depending on which sequencing method were used, one could estimate very different numbers of olfactory receptors. The authors also discovered that aside from sequencing the genome to very high coverage and at great cost, targeted sequence capture recovered 80-90% of the receptors, at a fraction (~1%) of the cost. This variation in methods can strongly change our interpretation of what constitutes a “good smeller”, and comparisons of numbers from various sequencing methods might mislead our understanding of the evolution of the sense of smell.
Besides showing a cost-effective way of sequencing olfactory receptors in mammals, the authors advocate comparing sequences shared across species to better understand the evolution of gene duplications. Although studies often compare the number of receptors, examining changes in the sequence and their location in duplicated receptors can be more informative, and this is now possible for many more species thanks to the approach developed by Yohe, et al. (2019).
Yohe, L. R., Davies, K. T., Simmons, N. B., Sears, K. E., Dumont, E. R., Rossiter, S. J. and Dávalos, L. M. (2019), Evaluating the performance of targeted sequence capture, RNA‐Seq, and degenerate‐primer PCR cloning for sequencing the largest mammalian multigene family. Mol Ecol Resour. Accepted Author Manuscript. doi:10.1111/1755-0998.13093