Abstract
One of the central goals of evolutionary biology is to explain and predict the molecular basis of adaptive evolution. We studied the evolution of genetic networks in Saccharomyces cerevisiae (budding yeast) populations propagated for more than 200 generations in different nitrogen-limiting conditions. We find that rapid adaptive evolution in nitrogen-poor environments is dominated by the de novo generation and selection of copy number variants (CNVs), a large fraction of which contain genes encoding specific nitrogen transporters including PUT4, DUR3 and DAL4. The large fitness increases associated with these alleles limits the genetic heterogeneity of adapting populations even in environments with multiple nitrogen sources. Complete identification of acquired point mutations, in individual lineages and entire populations, identified heterogeneity at the level of genetic loci but common themes at the level of functional modules, including genes controlling phosphatidylinositol-3-phosphate metabolism and vacuole biogenesis. Adaptive strategies shared with other nutrient-limited environments point to selection of genetic variation in the TORC1 and Ras/PKA signaling pathways as a general mechanism underlying improved growth in nutrient-limited environments. Within a single population we observed the repeated independent selection of a multi-locus genotype, comprised of the functionally related genes GAT1, MEP2 and LST4. By studying the fitness of individual alleles, and their combination, as well as the evolutionary history of the evolving population, we find that the order in which these mutations are acquired is constrained by epistasis. The identification of repeatedly selected variation at functionally related loci that interact epistatically suggests that gene network polymorphisms (GNPs) may be a frequent outcome of adaptive evolution. Our results provide insight into the mechanistic basis by which cells adapt to nutrient-limited environments and suggest that knowledge of the selective environment and the regulatory mechanisms important for growth and survival in that environment greatly increase the predictability of adaptive evolution.
Highlights
The fields of evolutionary and molecular biology are fusing in a research program that has been termed the ‘‘functional synthesis’’ [1]
We reconstructed the evolutionary dynamics of a population evolving in ammonium-limited conditions and find that a multi-locus genotype is repeatedly selected within the population and constrained by epistasis. We propose that this genotype constitutes a ‘‘gene network polymorphism (GNP),’’ which may be a common outcome of adaptive evolution
Adapted clones have dramatically increased fitness Initially, we studied populations evolving in seven different nitrogen-limited environments
Summary
The fields of evolutionary and molecular biology are fusing in a research program that has been termed the ‘‘functional synthesis’’ [1]. The power of this approach is exemplified by the molecular reconstruction of ancestral proteins enabling the study of the functional properties [2] and evolutionary histories [3] of individual genes. The evolution of pathways and networks comprising multiple genes has far been less amenable to functional studies. This is due in part to the difficulty of inferring and engineering ancestral states of genetic networks. Experimental evolution using microbes has a number of useful features including the ability to monitor evolution in real time and to measure fitness in the relevant environmental condition [4] that makes it ideally suited to the study of gene network evolution
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