For decades following the modern synthesis in evolutionary biology, the
molecular details underlying the genotype-phenotype map have been treated
as a "black box." Propelled by new technologies, our ability to peer inside
the box is rapidly improving. Using a systems genetics framework, we can
now integrate genotypic and phenotypic variation with variation in
molecular endophenotypes (such as gene expression) to construct biological
networks that allow us to draw the causal path from variation in allele
frequencies to phenotypic differences between individuals. However, the
average allelic effect across individuals does not always capture the
effect of a specific allele under certain conditions. For example, both the
genetic background and environmental differences can lead to major
phenotypic differences among individuals sharing the same alleles. When
this occurs, current methods may not be able to detect the link between
genotype and phenotype -- this may help explain why we have fallen short of
the ultimate goal of explaining most of the heritability for complex traits
in terms of allelic effects. My research is dedicated to understanding the
context dependence of allelic effects in light of gene-gene and
genotype-by-environment interactions. While we have historically thought of
the genotype-phenotype map as a static blueprint underlying the phenotype,
the work I will present suggests that the blueprint itself is dynamic and
context-dependent. This perspective is particularly helpful when trying to
understand, for example, why some individuals appear to be more sensitive
than others to environmental perturbations. I will illustrate this point
using examples from my current work, and I will discuss the implication of
these findings in the context of evolutionary response and our
understanding of the genetic basis of complex traits.