Big Insights From Blind Fish

November 21, 2016

Grand Challenges team integrates genomic techniques to reveal mechanisms of adaptation in Mexican cave fish populations.

Peter Tiffin, Courtney Passow, Suzanne McGaugh

From left: Peter Tiffin, Courtney Passow, Suzanne McGaugh

The last in a four-part series on the first round of research projects funded through the College of Biological Sciences' Grand Challenges in Biology Postdoctoral Program.

Understanding precisely how genomic information translates to phenotypic expression would fuel high-impact possibilities for research in adaptation and evolution, embryonic development, and human health. Yet modern science lacks satisfactory explanations for the esoteric processes that transform genes into functional organisms.

“The interactions between genetic systems are complex,” says Courtney Passow, one of four post-doctoral associates selected as part of the first cohort of the college's Grand Challenges in Biology Postdoctoral Program. Emergent research techniques continually provide new insights into individual layers of the process. Some researchers analyze raw DNA sequence data, others examine gene expression data, still others look at protein translation and function. All of these disciplines are essential, yet how they fit together is often unclear.

“Our project aims to integrate across multiple fields and combine them to get a bigger picture of mechanisms that actually cause organisms to develop in specific ways,” says Passow, whose Grand Challenges project will investigate genetic mechanisms that underpin adaptation in an unusual fish species, Astyanax mexicanus.

After studying fish behavior and genetics as an undergraduate student, Passow’s Ph.D. thesis examined extremophile fish that have adapted to survive in pools of hydrogen sulfide. Consequently, she brings eight years of expertise in bony fish to the table. Astyanax presents two distinct but crossable populations — some that dwell in surface lakes, and some that live in subterranean caves. Passow joins Suzanne McGaugh, faculty in the Department of Ecology, Evolution and Behavior, and Peter Tiffin, faculty in Plant and Microbial Biology for her ambitious project.

“Mexican cave fish are particularly interesting because they provide us an opportunity to pick apart phenotypes that we don't have in other systems,” says McGaugh, whose lab gathers, sequences and analyzes dozens of Astyanax genomes from multiple populations. Whereas surface fish develop normal vision, embryonic cave fish initially develop eyes, but these early eyes regress through development, resulting in complete blindness. Surface and cave fish also diverge extensively in physical appearance, sleep patterns, and social behavior.

Passow aims to unpack the mechanisms behind some of these adaptations by building models of “co-expression networks” in Astyanax — i.e. an understanding of how specific groups of genes are synchronously up- or down-regulated during development. She will likewise examine “outlier loci” — i.e. genes that have diverged beyond what would be expected if natural selection had not been operating. These diverged genes can sometimes tell important stories about how adaptation occurred.

Integrating these techniques to tell a more cohesive story is certainly nuanced and tricky, yet Passow’s collaborators offer substantial expertise and insight. McGaugh uses statistical genomic analyses to learn about pathways involved in stress, metabolism, and life history evolution in cave fish specifically. Tiffin, on the other hand, brings expertise in genome-wide analyses performed in plant and microbial communities.

“On this project team, all three of us are explicitly coming from different directions,” says Tiffin, who has never worked in animals before. “There will be numerous opportunities for cross-talk between plant, microbial, and animal research communities, and that should provide insight and interesting ideas that we wouldn't have if we stayed only within one research community.”

“The cave fish community is one of the most collegial I've ever worked with,” says Passow. “There's a tremendous amount of collaboration, and there's no way we could do these projects without that.”  —Colleen Smith

“Mexican cave fish are particularly interesting because they provide us an opportunity to pick apart phenotypes that we don't have in other systems.”  —Suzanne McGaugh