Exposing the fitness contribution of duplicated genes

Abstract

Duplicate genes from the whole-genome duplication (WGD) in yeast are often dispensable--removing one copy has little or no phenotypic consequence. It is unknown, however, whether such dispensability reflects insignificance of the ancestral function or compensation from paralogs. Here, using precise competition-based measurements of the fitness cost of single and double deletions, we estimate the exposed fitness contribution of WGD duplicate genes in metabolism and bound the importance of their ancestral pre-duplication function. We find that the functional overlap between paralogs sufficiently explains the apparent dispensability of individual WGD genes. Furthermore, the lower bound on the fitness value of the ancestral function, which is estimated by the degree of synergistic epistasis, is at least as large as the average fitness cost of deleting single non-WGD genes. These results suggest that most metabolic functions encoded by WGD genes are important today and were also important at the time of duplication.

Small-scale copy number variation and large-scale changes in gene expression

“…According to the theory of neofunctionalization, duplicated genes are initially redundant, and, on occasion, one of a duplicate pair may diverge to perform some new function (8). In fact, the number of retained gene duplicate pairs is unexpectedly high, with extensive experimental evidence that duplicate genes retain functional compensation over long periods of time (4,51,52). Duplicated genes or motifs may not be strictly redundant, even initially.…”

“…The copy number of genes and gene fragments varies significantly over physiological to evolutionary time scales with multiple effects on phenotype. For example, CNV can cause statistically significant changes in concentrations of RNA associated with growth rate changes in bacteria (1,2) and enzyme concentrations associated with nutrient intake in humans (3,4). The copy number of viral genomes undergoes dynamical changes during multiple infection of bacteria by phages, leading to qualitative changes in gene regulation that may lead to alternative modes of exploitation (5,6).…”

Experimental illumination of a fitness landscape

“…To validate our EMPIRIC approach, we experimentally determined the fitness effects of six point mutants through binary competition of strains fluorescently labeled with either CFP or YFP as described (35). Briefly, the CFP and YFP genes were chromosomally integrated into the iG170D parental yeast strain used in the EMPIRIC measurements.…”

Accelerated evolution of resistance in multidrug environments

“…For each pair, drugs were mixed in a two-dimensional array of wells in which the concentration of each of the single drugs varied from zero to above its MIC. Populations derived from clonal expansion of a single wild-type, drug-sensitive E. coli bacterium were introduced to all wells and propagated through daily serial transfers (see Materials and Methods) (23)(24)(25). The rates at which bacterial populations developed residual resistance to the various drug combinations were measured by tracking the evolution of these populations over Ϸ170 generations (Fig.…”