High-Throughput Identification of Adaptive Mutations in Experimentally Evolved Yeast Populations

Payen, Célia; Sunshine, Anna B.; Ong, Giang T.; Pogachar, Jamie L.; Zhao, Wei; Dunham, Maitreya J.

doi:10.1371/journal.pgen.1006339

Cited by 76 publications

(92 citation statements)

References 77 publications

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“…To determine the impact of duplicated genes, we examined growth fitness of the WT strain with low (∼2–3 gene copies) or high (∼8–24 gene copies) plasmid CN, where each plasmid contained a single gene of interest from previously published data, relative to WT (File S6 in File S1, Figure S15 in File S2, and Payen et al 2016). …”

Section: Resultsmentioning

confidence: 99%

Extensive Copy Number Variation in Fermentation-Related Genes AmongSaccharomyces cerevisiaeWine Strains

Steenwyk

Rokas

2017

G3 Genes|Genomes|Genetics

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Due to the importance of Saccharomyces cerevisiae in wine-making, the genomic variation of wine yeast strains has been extensively studied. One of the major insights stemming from these studies is that wine yeast strains harbor low levels of genetic diversity in the form of single nucleotide polymorphisms (SNPs). Genomic structural variants, such as copy number (CN) variants, are another major type of variation segregating in natural populations. To test whether genetic diversity in CN variation is also low across wine yeast strains, we examined genome-wide levels of CN variation in 132 whole-genome sequences of S. cerevisiae wine strains. We found an average of 97.8 CN variable regions (CNVRs) affecting 4% of the genome per strain. Using two different measures of CN diversity, we found that gene families involved in fermentation-related processes such as copper resistance (CUP), flocculation (FLO), and glucose metabolism (HXT), as well as the SNO gene family whose members are expressed before or during the diauxic shift, showed substantial CN diversity across the 132 strains examined. Importantly, these same gene families have been shown, through comparative transcriptomic and functional assays, to be associated with adaptation to the wine fermentation environment. Our results suggest that CN variation is a substantial contributor to the genomic diversity of wine yeast strains, and identify several candidate loci whose levels of CN variation may affect the adaptation and performance of wine yeast strains during fermentation.

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Section: Resultsmentioning

confidence: 99%

Extensive Copy Number Variation in Fermentation-Related Genes AmongSaccharomyces cerevisiaeWine Strains

Steenwyk

Rokas

2017

G3 Genes|Genomes|Genetics

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“…Alternatively, if emerging ORFs mostly correspond to spurious non-genic ORFs with no role in de novo gene birth, increasing their expression level should generally be neutral or toxic, and not provide fitness benefits. Systematic overexpression screens have been shown to recapitulate the outcomes laboratory evolution 8 experiments 23 . We thus developed a dedicated overexpression screening strategy to identify ORFs that increased relative fitness upon increased expression, whereby colony sizes of individual overexpression strains were compared with those of hundreds of replicates of a reference strain with the same genetic background on ultra-high-density arrays ( Fig.…”

Section: Adaptive Potentialmentioning

confidence: 99%

De novoemergence of adaptive membrane proteins from thymine-rich intergenic sequences

Vakirlis

Acar

Hsu

et al. 2019

Preprint

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Recent evidence demonstrates that novel protein-coding genes can arise de novo from intergenic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of intergenic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Do intergenic translation events yield polypeptides with useful biochemical capacities?The answer to this question remains controversial. Here, we systematically characterized how de novo emerging coding sequences impact fitness. In budding yeast, overexpression of these sequences was enriched in beneficial effects, while their disruption was generally inconsequential.We found that beneficial emerging sequences have a strong tendency to encode putative transmembrane proteins, which appears to stem from a cryptic propensity for transmembrane signals throughout thymine-rich intergenic regions of the genome. These findings suggest that novel genes with useful biochemical capacities, such as transmembrane domains, tend to evolve de novo within intergenic loci that already harbored a blueprint for these capacities. 3 The molecular mechanisms and dynamics of de novo gene birth are poorly understood 1 . It is particularly unclear how non-genic sequences could spontaneously encode proteins with specific and useful biochemical capacities. To resolve this paradox, it has been proposed that pervasive translation of non-genic transcripts can expose genetic variation, in the form of novel polypeptides, to natural selection, thereby purging toxic sequences and providing adaptive potential to the 5 organism 2,3 . The genomic sequences encoding these novel polypeptides have been called "protogenes", to denote that they correspond to a distinct class of genetic elements that are intermediates between non-genic sequences and established genes 3 . In agreement, several studies reported that de novo emerging coding sequences tend to display lengths, transcript architectures, transcription levels, strength of purifying selection, sequence compositions, structural features and integration 10 in cellular networks that are intermediate between those observed in non-genic sequences and those observed in established genes 3-8 . Furthermore, pervasive translation of non-genic sequences has been observed repeatedly by ribosome profiling and proteo-genomics 3,[9][10][11][12] , and studies have shown that random sequence libraries harbor bioactive effects [13][14][15][16][17] . Nonetheless, whether and how native proto-genes carry adaptive potential remains unknown. 15 We sought to formalize the predictions of adaptive proto-gene evolution. We define adaptive potential as the capacity to increase fitness by means of evolutionary change. While any sequence may in theory carry adaptive potential, changes in established genes are typically constrained by preexisting selected effects -the specific physiological processes mediated by the gene products that lead to their evolutionary conservation 18 . In contrast, emerging proto-genes are 20 expected to mostly lack ...

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“…The identification and characterization of the genetic mechanisms underlying adaptive evolution remains a central challenge in biology. To identify beneficial mutations, recent studies have characterized thousands of first-step mutations and systematic deletion and amplification mutations in the yeast genome (1,2). These unbiased screens provide a wealth of information regarding the spectrum of beneficial mutations, their fitness effects, and the biological processes under selection.…”

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confidence: 99%

Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

Buskirk

Peace

Lang

2017

Proc. Natl. Acad. Sci. U.S.A.

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Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we use a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally evolved yeast populations. We report that nearly 80% of detected mutations have no discernible effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intracohort synergistic epistasis between alleles of hsl7 and kel1, which arose together in a low-frequency lineage.experimental evolution | cohorts | fitness | epistasis A daptation is a fundamental biological process. The identification and characterization of the genetic mechanisms underlying adaptive evolution remains a central challenge in biology. To identify beneficial mutations, recent studies have characterized thousands of first-step mutations and systematic deletion and amplification mutations in the yeast genome (1, 2). These unbiased screens provide a wealth of information regarding the spectrum of beneficial mutations, their fitness effects, and the biological processes under selection. However, this information alone cannot predict which mutations will ultimately succeed in an evolutionary context as genetic interactions and population dynamics also impart substantial influence on the adaptive outcomes.Early theoretical models assume that beneficial mutations are rare, such that once a beneficial mutation escapes drift, it will fix (3-5). For most microbial populations, however, multiple beneficial mutations will arise and spread simultaneously, leading to complex dynamics of clonal interference and genetic hitchhiking (6-9), and in many cases, multiple mutations track tightly with one another through time as mutational cohorts (10-13). The fate of each mutation is therefore dependent not only on its own fitness effect, but on the fitness effects of and interactions between all mutations in the population. Many beneficial mutations will be lost due to drift and clonal interference, whereas many neutral (and even deleterious) mutations will fix by hitchhiking. The influence of clonal interference and genetic hitchhiking on the success of mutations makes it difficult to identify beneficial mutations from sequenced clones or population samples. The extent of genetic hitchhiking and its evolutionary significanc...

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High-Throughput Identification of Adaptive Mutations in Experimentally Evolved Yeast Populations

Cited by 76 publications

References 77 publications

Extensive Copy Number Variation in Fermentation-Related Genes AmongSaccharomyces cerevisiaeWine Strains

Extensive Copy Number Variation in Fermentation-Related Genes AmongSaccharomyces cerevisiaeWine Strains

De novoemergence of adaptive membrane proteins from thymine-rich intergenic sequences

Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

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