Research Interest

Intra- and interspecific variation in gene regulation

Differences in gene expression observed between species (and variation for gene expression within species) may be caused by changes in cis regulatory regions or by divergence of trans-acting factors. The degree to which cis, trans or cis-trans interactions account for variation in gene expression is currently unclear. Between species expression divergence appears to be explained predominantly by cis differences. However, expression variation within species appears to be explained mostly by trans effects. This may indicate a difference in the relative contributions of cis and trans differences to variation within and between species or it may simply be attributable to differences in the experimental methods and numbers of genes sampled.

The goal of my current research is to develop the tools necessary to assay the relative contribution of cis, trans, and cis-trans effects to within (and between) species variation in gene expression, at the genomic level. In the McIntyre lab, we are developing methods to estimate these components of regulatory variation both from currently available commercial microarray designs and from our own custom designs. The custom platform we are developing is a modified SNP chip design which will allow us to estimate allele specific expression levels in D. simulans for most currently annotated transcripts. With these new tools and models in hand we hope to address fundamental questions about the quantitative genetics of allele specific expression. Is allele-specific expression generally additive, or is there a significant role for dominance and epistasis? What is the intersection between these modes of inheritance and underlying cis, trans and cis- trans components of regulatory variation? I am also addressing similar questions using a tiling array platform to compare the components of variation and divergence in transcript level by assaying allele-specific expression in D. melanogaster, D.simulans and their F1 hybrids. The long-term goal of this body of work is to understand how such, potentially complex, variation in gene regulation contributes to variation in regulatory pathways as a whole and eventually to downstream differences in quantitative morphological, behavioral and physiological traits.