Wittkopp Patricia J, Haerum Belinda K, Clark Andrew G
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Nat Genet. 2008 Mar;40(3):346-50. doi: 10.1038/ng.77. Epub 2008 Feb 17.
Differences in gene expression are an important source of phenotypic variation, and can be caused by changes in cis and/or trans regulation. cis-regulatory variants alter allele-specific expression, whereas trans-regulatory variants influence expression of both alleles in a diploid cell. Because of this difference, we hypothesize that natural selection may favor one type of change over the other. Here, we investigate contributions of cis- and trans-regulatory changes to variable intra- and interspecific gene expression using four strains of Drosophila melanogaster, three strains of D. simulans and a total of 78 genes. We show that cis-regulatory changes account for a greater proportion of the expression differences observed between rather than within species. These data are inconsistent with a neutral model assuming equal probabilities of fixation for cis- and trans-regulatory polymorphisms, suggesting that natural selection influences the molecular mechanisms underlying divergent gene expression. Specifically, cis-regulatory changes seem to accumulate preferentially over time.
基因表达差异是表型变异的一个重要来源，可能由顺式和/或反式调控的变化引起。顺式调控变异改变等位基因特异性表达，而反式调控变异影响二倍体细胞中两个等位基因的表达。由于这种差异，我们推测自然选择可能更倾向于一种类型的变化而非另一种。在这里，我们使用四株黑腹果蝇、三株拟果蝇以及总共78个基因，研究顺式和反式调控变化对种内和种间可变基因表达的贡献。我们表明，顺式调控变化在物种间而非物种内观察到的表达差异中占更大比例。这些数据与假设顺式和反式调控多态性固定概率相等的中性模型不一致，表明自然选择影响基因表达差异背后的分子机制。具体而言，顺式调控变化似乎随时间优先积累。
