Compensatory cis-trans Evolution and the Dysregulation of Gene Expression in Interspecific Hybrids of Drosophila

Abstract

Hybrids between species are often characterized by novel gene-expression patterns. A recent study on allele-specific gene expression in hybrids between species of Drosophila revealed cases in which cis-and transregulatory elements within species had coevolved in such a way that changes in cis-regulatory elements are compensated by changes in trans-regulatory elements. We hypothesized that such coevolution should often lead to gene misexpression in the hybrid. To test this hypothesis, we estimated allele-specific expression and overall expression levels for 31 genes in D. melanogaster, D. simulans, and their F 1 hybrid. We found that 13 genes with cis-trans compensatory evolution are in fact misexpressed in the hybrid. These represent candidate genes whose dysregulation might be the consequence of coevolution of cis-and trans-regulatory elements within species. Using a mathematical model for the regulation of gene expression, we explored the conditions under which cis-trans compensatory evolution can lead to misexpression in interspecific hybrids.

Complex genetic interactions underlying expression differences between Drosophila races: Analysis of chromosome substitutions

“…We have shown in Table 1 that the contribution of interactive terms to expression variation between populations is Ͼ30% and can be as large as 50%. In the analysis of interspecific F 1 hybrids, Landry et al (5) have shown that 13 of the 23 misexpressed genes exhibited cis-bytrans interaction. Furthermore, cis and trans factors can interact in opposition to each other.…”

“…(cis regulation refers to the control of expression by the gene itself whereas trans regulation refers to the influence of the genetic background.) Many studies have addressed this question at various levels of divergence (1)(2)(3)(4)(5)(6)(7)(8)(9). For example, one may measure the expressions of two alleles at the locus of interest in a common genetic background (usually F 1 s) (1,2,5).…”

Linking transcriptomic and genomic variation to growth in brook charr hybrids (Salvelinus fontinalis, Mitchill)

“…Here, because allelic expression was analyzed in hybrids, only cis-regulatory differences could be detected. In order to detect trans-regulatory effects, it would have been necessary to study allelic expression in not only hybrids but also parental populations at the same life stage, which was not possible here (Wittkopp et al, 2004;Landry et al, 2005;Fraser et al, 2011). We therefore preferred to increase coverage for the hybrid crosses in order to at least more rigorously confirm the occurrence of cis regulation, as directly reflected by significant allelic imbalance in hybrids.…”

“…For example, dominance in gene expression inheritance has been significantly associated with trans regulatory elements (Lemos et al, 2008). Finally, gene expression regulation can be affected by the interaction of both regulatory systems, either through trans by trans or through cis by trans interactions (Landry et al, 2005).…”

“…Allelic imbalance is caused by the direct influence of cis-regulatory elements. On the other hand, we may conclude to the presence of trans-regulatory effects when the following two conditions are met: (1) no allelic imbalance is observed in heterozygous individuals, as trans-regulatory elements affect both alleles in the same manner, and (2) when homozygous individuals possessing the same allele and originating from different populations show differences in allelic expression levels (Wittkopp et al, 2004;Landry et al, 2005).…”