PgmNr Y469: A cradle-to-grave analysis of cis-regulatory variation in yeast.

Authors:
J. M. Andrie; G. E. Merrihew; J. Madeoy; D. S. Gordon; D. Akey; E. E. Eichler; D. R. Morris; J. Wakefield; M. MacCoss; J. M. Akey


Institutes
University of Washington, Seattle, WA.


Keyword: Translation

Abstract:

Cis-regulatory variation is an important source of phenotypic variation within populations and a major target of adaptive divergence between species. However, the molecular processes that are influenced by cis-regulatory variation remain poorly understood. To this end, we crossed two genetically diverse wild-derived strains of Saccharomyces cerevisiae and studied allele-specific differences in eight molecular phenotypes, including chromatin structure, rates of RNA transcription, decay and translation, RNA secondary structure, binding of proteins to RNA, steady-state protein abundance, and protein decay rates. Furthermore, we performed high-coverage sequencing of both the genome (using PacBio) and the transcriptome, and de novo assembled each parental strain to mitigate read mapping biases and ensure accurate estimates of allele-specific phenotypes. We show that cis-regulatory variation has pervasive effects on high-dimensional molecular phenotypes, and pleiotropy and buffering are predominant features in the architectural landscape of cis-regulatory mutations. Our comprehensive data also provides novel mechanistic insights into cis-regulatory variation. We anticipate that our data will be of considerable general interest, and a powerful resource to test hypotheses about the evolution of cis-regulatory variation.