Epistasis Blog

From the Artificial Intelligence Innovation Lab at Cedars-Sinai Medical Center (www.epistasis.org)

Wednesday, January 26, 2011

Yeast genetics is complex. What about humans?

This is a nice new paper documenting the genetic complexity of yeast. This adds to the growing body of literature highlighting the importance of gene-gene and gene-environment interactions in model organisms. I continue to raise the question as to why the field of human genetics continues to downplay such effects in humans. Do we really expect human have simpler genetic archtectures that yeast and other lower organisms?

Cubillos FA, Billi E, Zörgö E, Parts L, Fargier P, Omholt S, Blomberg A, Warringer J, Louis EJ, Liti G. Assessing the complex architecture of polygenic traits in diverged yeast populations. Mol Ecol. 2011 Jan 25. [Epub ahead of print] PubMed PMID: 21261765. [PubMed]


Phenotypic variation arising from populations adapting to different niches has a complex underlying genetic architecture. A major challenge in modern biology is to identify the causative variants driving phenotypic variation. Recently, the baker's yeast, Saccharomyces cerevisiae has emerged as a powerful model for dissecting complex traits. However, past studies using a laboratory strain were unable to reveal the complete architecture of polygenic traits. Here, we present a linkage study using 576 recombinant strains obtained from crosses of isolates representative of the major lineages. The meiotic recombinational landscape appears largely conserved between populations; however, strain-specific hotspots were also detected. Quantitative measurements of growth in 23 distinct ecologically relevant environments show that our recombinant population recapitulates most of the standing phenotypic variation described in the species. Linkage analysis detected an average of 6.3 distinct QTLs for each condition tested in all crosses, explaining on average 39% of the phenotypic variation. The QTLs detected are not constrained to a small number of loci, and the majority are specific to a single cross-combination and to a specific environment. Moreover, crosses between strains of similar phenotypes generate greater variation in the offspring, suggesting the presence of many antagonistic alleles and epistatic interactions. We found that subtelomeric regions play a key role in defining individual quantitative variation, emphasizing the importance of the adaptive nature of these regions in natural populations. This set of recombinant strains is a powerful tool for investigating the complex architecture of polygenic traits.


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