It is well established in quantitative genetics that stressful environmental exposure tends to increase the phenotypic variance of a population, but how and why? And why do some individuals appear to be more sensitive than others to such perturbations?
This is a fundamental question for any biologist interested in understanding the genetic basis of variation for complex trait. Although studies of development, morphology and animal breeding have long noted the heterogeneity of variance among genotypes, this axis of variation has received little attention compared to the effect of genetic variation on trait means. There is now clear evidence for the importance of genetic control of variance and that variance itself is a quantitative trait. This has important implications both in medical genetics and evolutionary biology. If different genetic backgrounds differ in their propensity for phenotypic variability, then individuals derived from a high-variability genetic background may exhibit an extreme phenotype by chance alone. A property of that genotype that would not have been informed by traditional mean focused quantitative genetic approaches. In the context of evolutionary change, this could accelerate or slow down adaptation to new conditions. With respect to health, this could result in disease, changes in variance can affect the probability of individuals finding itself in the tails of the distribution. Therefore, by focusing primarily on the effect of genetic variation on trait averages and ignoring its effect on variance, we may be missing a very important axis contributing to phenotypic variation.
Our lab explores this problem both from an evolutionary perspective asking: under what scenario might variance control evolve? What evolutionary forces maintain variation for alleles controlling phenotypic variability? And from a medical perspective: how does variance control affect our ability to make predictions from genotype to phenotype? Does the presence of variance increasing alleles increase increase the probability an individual being in the tail of distribution?
Collaborators:
Evolutionary dynamics of variability
Benjamin de Bivort Lab (Harvard)
Robustness As A Driver Of Disease Emergence
Paivi Pajukanta Lab (UCLA)
Noah Zaitlen Lab (UCSF)