Rare variants contribute disproportionately to quantitative trait variation in yeast
Abstract
How variants with different frequencies contribute to trait variation is a central question in genetics. We use a unique model system to disentangle the contributions of common and rare variants to quantitative traits. We generated ~14,000 progeny from crosses among 16 diverse yeast strains and identified thousands of quantitative trait loci (QTLs) for 38 traits. We combined our results with sequencing data for 1,011 yeast isolates to show that rare variants make a disproportionate contribution to trait variation. Evolutionary analyses revealed that this contribution is driven by rare variants that arose recently, and that negative selection has shaped the relationship between variant frequency and effect size. We leveraged the structure of the crosses to resolve hundreds of QTLs to single genes. These results refine our understanding of trait variation at the population level and suggest that studies of rare variants are a fertile ground for discovery of genetic effects.
Data availability
Unless otherwise specified, all computational analyses were performed in R (v3.4.4). Analysis code and processing scripts are available at https://github.com/joshsbloom/yeast-16-parents. Additional links to generated data are also provided in the github repository. The version numbers of R packages used are listed in this repository. Sequencing data has been deposited in the SRA under the accession code PRJNA549760.
Article and author information
Author details
Funding
National Institutes of Health (R01GM102308)
- Joshua S Bloom
- Meru J Sadhu
- Laura Day
- Holly Oates-Barker
- Leonid Kruglyak
Howard Hughes Medical Institute
- Joshua S Bloom
- Laura Day
- Holly Oates-Barker
- Leonid Kruglyak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Bloom et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Genetics and Genomics
Rare genetic variants in yeast explain a large amount of phenotypic variation in a complex trait like growth.
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- Genetics and Genomics
eLife publishes advances in quantitative genetics, including the genetic basis of complex traits, the maintenance of genetic variation, and their roles in evolution.