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Abstract
Understanding the genetic basis of gene regulatory variation is a key goal of evolutionary and medical genetics. Regulatory variation can act in an allele-specific manner (cis-acting) or it can affect both alleles of a gene (trans-acting). Differential allele-specific expression (ASE), in which the expression of one allele differs from another in a diploid, implies the presence of cis-acting regulatory variation. While microarrays and high-throughput sequencing have enabled genome-wide measurements of transcriptional ASE, methods for measurement of protein ASE (pASE) have lagged far behind. We describe a flexible, accurate, and scalable strategy for measurement of pASE by liquid chromatography-coupled mass spectrometry (LC-MS). We apply this approach to a hybrid between the yeast species Saccharomyces cerevisiae and Saccharomyces bayanus. Our results provide the first analysis of the relative contribution of cis-acting and trans-acting regulatory differences to protein expression divergence between yeast species.
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1 Department of Computer Science, Princeton University, Princeton, NJ, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
2 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA
3 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA; Princeton Mass Spectrometry Center, Princeton University, Princeton, NJ, USA
4 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
5 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA; Howard Hughes Medical Institute, Princeton University, Princeton, NJ, USA