Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS.
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.
Department of Computer Science, Princeton University, Princeton, NJ 08544, USA. zia@uchicago.edu
Zia
Z
Khan
Joshua S
JS
Bloom
Sasan
S
Amini
Mona
M
Singh
David H
DH
Perlman
Amy A
AA
Caudy
Leonid
L
Kruglyak
D000483:Alleles; D002853:Chromatography, Liquid / Q000379:methods; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D040901:Proteomics / Q000379:methods*; D012044:Regression Analysis; D012440:Saccharomyces / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins