Dataset Information

A general calculus of fitness landscapes finds genes under selection in cancers.

ABSTRACT: Genetic variants drive the evolution of traits and diseases. We previously modeled these variants as small displacements in fitness landscapes and estimated their functional impact by differentiating the evolutionary relationship between genotype and phenotype. Conversely, here we integrate these derivatives to identify genes steering specific traits. Over cancer cohorts, integration identified 460 likely tumor-driving genes. Many have literature and experimental support but had eluded prior genomic searches for positive selection in tumors. Beyond providing cancer insights, these results introduce a general calculus of evolution to quantify the genotype-phenotype relationship and discover genes associated with complex traits and diseases.

SUBMITTER: Hsu TK

PROVIDER: S-EPMC9104707 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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A general calculus of fitness landscapes finds genes under selection in cancers.

Hsu Teng-Kuei TK Asmussen Jennifer J Koire Amanda A Choi Byung-Kwon BK Gadhikar Mayur A MA Huh Eunna E Lin Chih-Hsu CH Konecki Daniel M DM Kim Young Won YW Pickering Curtis R CR Kimmel Marek M Donehower Lawrence A LA Frederick Mitchell J MJ Myers Jeffrey N JN Katsonis Panagiotis P Lichtarge Olivier O

Genome research 20220317 5

Genetic variants drive the evolution of traits and diseases. We previously modeled these variants as small displacements in fitness landscapes and estimated their functional impact by differentiating the evolutionary relationship between genotype and phenotype. Conversely, here we integrate these derivatives to identify genes steering specific traits. Over cancer cohorts, integration identified 460 likely tumor-driving genes. Many have literature and experimental support but had eluded prior gen ...[more]

PMID: 35301263

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Project description:Habitat selection theory suggests that when choosing breeding sites, animals should choose the best available habitat; however, studies show that individuals fail to choose habitats that maximize their fitness especially in drastically altered landscapes. Many studies have focused on selection at single scales, often using a single measure of fitness. However, links between habitat selection and fitness may vary depending on the spatial scale and measure of fitness, especially in situations where agricultural land use has altered the surrounding landscape.We examined multiscale habitat selection and fitness measures of the Bell's Vireo (Vireo bellii) and Willow Flycatcher (Empidonax traillii) using data collected in agriculturally fragmented landscapes.We found evidence for selection of nest sites with dense understory, larger patches, and increasing restored habitat cover and decreasing forest cover in the surrounding landscape.For both focal species, selection for dense understory significantly increased nest survival; however, there appeared to be no concurrent benefit for fledgling production. Selection for broader scale features positively influenced nest survival for the Willow Flycatcher with no concurrent benefit for fledgling production. The observed mismatches may be due to anthropogenic habitat fragmentation at broader scales or may represent reproductive trade-offs for a fitness benefit not measured in this study.Fine-scale habitat selection decisions by our focal species appear to match fitness outcomes, whereas habitat selection at broader scales only provided fitness benefits for the Willow Flycatcher. Though providing no fledgling production benefit, when combined with suitably dense nesting habitat, larger patches in landscapes with greater amounts of restored habitat cover for Bell's Vireo and lower amounts of forest cover for Willow Flycatcher will produce more fledglings per unit area than smaller patches in landscapes with less restored habitat and more forest cover, respectively, which could help inform conservation decisions for these at-risk species.

Dataset Information

A general calculus of fitness landscapes finds genes under selection in cancers.

Publications

A general calculus of fitness landscapes finds genes under selection in cancers.

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