| 1. |
- Ibstedt, Sebastian, 1983, et al.
(författare)
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Concerted Evolution of Life Stage Performances Signals Recent Selection on Yeast Nitrogen Use.
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 32:1, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Exposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection. Critically, this test for selection requires fitness components to be determined by different genetic loci. To explore our conjecture, we exhaustively evaluated the lag, rate, and efficiency of asexual population growth of natural isolates of the model yeast Saccharomyces cerevisiae in a large variety of nitrogen-limited environments. Overall, fitness components were well correlated under nitrogen restriction. Yeast isolates were further crossed in all pairwise combinations and coinheritance of each fitness component and genetic markers were traced. Trait variations tended to map to quantitative trait loci (QTL) that were private to a single fitness component. We further traced QTLs down to single-nucleotide resolution and uncovered loss-of-function mutations in RIM15, PUT4, DAL1, and DAL4 as the genetic basis for nitrogen source use variations. Effects of SNPs were unique for a single fitness component, strongly arguing against pleiotropy between lag, rate, and efficiency of reproduction under nitrogen restriction. The strong correlations between life stage performances that cannot be explained by pleiotropy compellingly support adaptive differentiation of yeast nitrogen source use and suggest a generic approach for detecting selection.
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| 2. |
- Li, Jing, et al.
(författare)
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Shared Molecular Targets Confer Resistance over Short and Long Evolutionary Timescales
- 2019
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 36:4, s. 691-708
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Tidskriftsartikel (refereegranskat)abstract
- Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin, respectively. The causative pre-existing and de novo variants were selected on shared targets: RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. Interestingly, the pre-existing and de novo TOR variants map to different functional domains and act via distinct mechanisms. The pre-existing TOR variants from two domesticated strains exhibited opposite rapamycin resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how pre-existing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving populations.
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| 3. |
- Märtens, Kaspar, et al.
(författare)
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Predicting quantitative traits from genome and phenome with near perfect accuracy.
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- In spite of decades of linkage and association studies and its potential impact on human health, reliable prediction of an individual's risk for heritable disease remains difficult. Large numbers of mapped loci do not explain substantial fractions of heritable variation, leaving an open question of whether accurate complex trait predictions can be achieved in practice. Here, we use a genome sequenced population of ∼7,000 yeast strains of high but varying relatedness, and predict growth traits from family information, effects of segregating genetic variants and growth in other environments with an average coefficient of determination R(2) of 0.91. This accuracy exceeds narrow-sense heritability, approaches limits imposed by measurement repeatability and is higher than achieved with a single assay in the laboratory. Our results prove that very accurate prediction of complex traits is possible, and suggest that additional data from families rather than reference cohorts may be more useful for this purpose.
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