Faster-X Evolution of Gene Expression in <em>Drosophila</em>

DNA sequences on X chromosomes often have a faster rate of evolution when compared to similar loci on the autosomes, and well articulated models provide reasons why the X-linked mode of inheritance may be responsible for the faster evolution of X-linked genes. We analyzed microarray and RNA–seq data collected from females and males of six Drosophila species and found that the expression levels of X-linked genes also diverge faster than autosomal gene expression, similar to the “faster-X” effect often observed in DNA sequence evolution. Faster-X evolution of gene expression was recently described in mammals, but it was limited to the evolutionary lineages shortly following the creation of the therian X chromosome. In contrast, we detect a faster-X effect along both deep lineages and those on the tips of the Drosophila phylogeny. In Drosophila males, the dosage compensation complex (DCC) binds the X chromosome, creating a unique chromatin environment that promotes the hyper-expression of X-linked genes. We find that DCC binding, chromatin environment, and breadth of expression are all predictive of the rate of gene expression evolution. In addition, estimates of the intraspecific genetic polymorphism underlying gene expression variation suggest that X-linked expression levels are not under relaxed selective constraints. We therefore hypothesize that the faster-X evolution of gene expression is the result of the adaptive fixation of beneficial mutations at X-linked loci that change expression level in cis. This adaptive faster-X evolution of gene expression is limited to genes that are narrowly expressed in a single tissue, suggesting that relaxed pleiotropic constraints permit a faster response to selection. Finally, we present a conceptional framework to explain faster-X expression evolution, and we use this framework to examine differences in the faster-X effect between Drosophila and mammals.相较于常染色体上的同源基因座，X染色体上的DNA序列通常具有更快的进化速率；诸多阐释充分的演化模型均表明，X连锁遗传模式或许正是X连锁基因进化更快的成因。我们对6个果蝇物种雌雄个体的微阵列（microarray）与RNA测序（RNA-seq）数据开展分析，结果发现X连锁基因的表达水平分化速率同样快于常染色体基因的表达水平，这与DNA序列演化中常见的"faster-X"效应类似。此前已有研究在哺乳动物中报道了基因表达的更快X进化现象，但该现象仅局限于真兽类X染色体形成后不久的演化支系中。与之形成鲜明对比的是，我们在果蝇系统发育树的深层支系与末端支系中均检测到了更快X效应。在果蝇雄性个体中，剂量补偿复合体（dosage compensation complex, DCC）会结合X染色体，进而形成独特的染色质环境，以促进X连锁基因的超表达。我们发现，剂量补偿复合体结合情况、染色质环境以及表达广度，均可预测基因表达进化的速率。此外，针对基因表达变异背后的种内遗传多态性的估算结果显示，X连锁基因的表达水平并未经历选择约束的松弛。据此我们提出假说：基因表达的更快X进化，源于X连锁基因座上发生的、可通过顺式作用改变表达水平的有益突变的适应性固定。这种适应性的基因表达更快X进化，仅局限于在单一组织中窄范围表达的基因，这表明多效性约束的松弛，使得这些基因能够更快响应选择压力。最后，我们提出了一套用于阐释基因表达更快X进化的概念框架，并借助该框架分析了果蝇与哺乳动物之间更快X效应的差异。