Early in my career, Richard Lewontin’s book The Genetic Basis of Evolutionary Change impressed me. In it, he introduced the concept of the Genotype-Phenotype map (GP map) – the web of causal pathways whereby genetic variation affects the phenotype. This struck me as dorm-room discussion cool, but not science practical, so I thought little about it for many years. Since then, I made myself first into a population geneticist, and then into a quantitative geneticist-the two extremes in evolutionary genetics. Population genetics treats genetic variation explicitly, but then assumes (or estimates) that we know something about fitness effects of that variation. Quantitative genetics incorporates the study of phenotypic variation that causes variation in fitness, but remains vague about the actual genetic variation that underlies phenotypic variation. The two disciplines remain stubbornly independent, as they effectively use incommensurate languages about evolution. The means to convert between them, however, is precisely the GP map.
My research program is now aimed at actually estimating the GP map that connects genetic and genomic variation with phenotypic variation in the Drosophila wing. What once seemed impractical now seems necessary. We can sequence genomes, but cannot readily determine which variants are affecting fitness, and more important how they might affect it. With a GP map, we could predict what genetic variation matters, and how phenotypes might respond to selection. Without it, we are limited to retrospective and correlative statements about evolution. Predictive ability is the central challenge of science: evolutionary biologists need to rise to that challenge, not ignore or dismiss it.
Work in my lab uses many techniques in pursuit of this goal:
|Artificial selection experiments (graduate student Jason Cassara, post-doc Geir Bolstad).|
|Manipulations of gene expression (post-docs Eladio Marquez, and Rosa Moscarella.|
|Developmental morphometrics (graduate student David Aponte).|
|Developmental modeling (post-doctoral researcher Alexis Matamoro-Vidal).|
|Genome-wide association studies|