Title: Assistant Professor of Genome Sciences, University of Washington
Education: PhD, University of Texas at Houston, 2002
Recommended by: Evan Eichler
Joshua Akey was interested in genetic variation long before he had filled out an application to graduate school. “Even when I was a kid, the thing that fascinated me the most was just looking around and seeing how much variation there was between humans, animals, and just different species in general,” says Akey. That fascination grew after his undergraduate days in a population genetics lab. “I quickly became appreciative of the perspective that population genetics and evolution has on explaining phenotypic diversity and natural populations,” he says.
Now that Akey has his own lab, he's set about trying to explain the connection between genetics and natural diversity. The goals of his lab are to gain an understanding of genetic variation patterns within and between species and by doing so, to address some fundamental problems in biology and evolution. Currently, Akey is conducting genome-wide analyses to uncover evolutionary forces that have shaped the human genome as well as the dog and yeast genomes. “In our human studies, we have primarily been focusing on identifying regions of the genome that have been affected by natural selection and then trying to correlate patterns of selection with patterns of phenotypic variation, ultimately connecting this to disease susceptibility,” says Akey.
He hopes to gain an understanding of the genetic structure of human populations and identify genes that result in disease susceptibility. “Signatures of selection delimit regions of the genome that are functionally important so by finding such regions, it might help to narrow in on places that are relevant to disease,” he says.
Akey is also interested in the incredible amount of variation across the canine species, which contains more than 400 different breeds. “I'm really fascinated by looking at the evolutionary history of dogs because of their extreme amount phenotypic diversity,” he says. So far, his lab has collected roughly 150 dog samples from 10 different breeds and has begun to integrate the signature of domestication in dogs, leaving him one step closer to illuminating how man's best friend became so friendly.
Publications of note
Earlier this year, Akey and his partners published a paper in Human Molecular Genetics entitled “TRPV6 exhibits unusual patterns of poly-morphism and divergence in worldwide populations.” For this study, the researchers conducted a population genetic analysis of TRPV6, a calcium-permeable ion channel believed to mediate part of the calcium absorption process in humans. The paper showed that the rate of the channel’s evolution is accelerated in the human lineage, but only for a haplotype defined by three non-synonymous SNPs that are virtually fixed for the derived alleles in non-African populations. Their data suggested that the TRPV6 haplotype has a selective advantage that varied spatially during human history.
Akey says that locating hundreds of gene loci that appear to have been targets of natural selection is no problem. The stumbling block lies in moving beyond what he calls “superficial” genome-wide analyses and understanding the evolutionary history of each locus. “I think it's really important to begin to have more in-depth, focused studies on these regions, because otherwise you're left with this kind of unsatisfying list of places in genomes that might have been subject to selection — or maybe they're just outliers because of the nature of evolution,” says Akey.
For Akey, writing a Perl script and looking through the genome for unusual patterns of variation is easy. The hard part is connecting that variation to a functional effect and phenotype. “I think that the next five to 10 years will be spent in following up these analyses that have arisen from a genomics perspective and then actually understanding the biology and biomedical significance associated with them,” he says.