Abstract

Much of the variation in traits between closely related organisms is due to changes in gene expression, making the identification of the underlying genetic changes responsible for the gene expression changes a key goal of molecular biology. Gene expression levels are thought to diverge due to genetic variants that affect regulatory DNA , frequently in the vicinity of the gene and hence known as acting in cis, or due to more distal genetic variants that affect diffusible factors which in turn regulate the gene, known as acting in trans.

In this talk I will describe the work I have done with collaborators to assess which mode of regulation, in cis or in trans, is prevalent in mammalian speciation. In our work we measured gene expression divergence between two closely related mouse strains and in their progeny and identified many genes with divergent expression. Of these, a small minority could be attributed purely to variants acting in trans, while 43% were attributable only to variants acting in cis. The remaining genes with divergent patterns of expression were regulated by a combination of variants acting in cis and variants acting in trans. Intriguingly, the changes in expression induced by the cis and trans variants were in opposite directions more frequently than expected by chance, implying that compensatory regulation to stabilise gene expression levels is widespread. We propose that expression levels of genes regulated by this mechanism are fine-tuned by cis variants that arise following regulatory changes in trans, suggesting that many cis variants are not the primary targets of natural selection.