Does evolution use complex suites of regulatory mutations to create new traits?

22 Nov 2013

Rachel Brem
Department of Molecular and Cell Biology
UC Berkeley


Species evolve new traits in response to the pressures of natural selection. Finding the molecular changes that underlie adaptation, amid a genome's worth of evolutionary noise, is a central goal of comparative genomics. In the simplest case, mutations in a single gene may confer a major reproductive advantage, and classical molecular-evolution tests can detect the sequence patterns left behind as such a gene sweeps through the population. Alternatively, multiple independent variants could together give rise to an adaptive trait – in some cases leaving little signature of natural selection at any single locus on its own. How often does adaptation proceed by the complex, polygenic route, and how do we find signatures of polygenic evolution in genomes? Recent work in my lab has sought to address these questions in the context of mRNA expression. We have developed empirical methods to detect polygenic suites of unlinked, independent gene regulatory changes. In yeast species, we find multi-gene pathways whose expression has been tuned by coherent cis- and trans-regulatory mutations to a degree unlikely under neutrality, some with strong signatures of selection in sequence-based tests. Our results dovetail with the emerging consensus in the field that divergence in gene expression between distant species can be attributed only rarely to master regulators that act upstream in gene networks. We thus propose that evolutionary novelties often emerge from independent mutations in the downstream nodes of a regulatory network, maximizing fitness by adjusting expression of effector genes in a pathway one by one.

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