Hoekstra Hopi E, Coyne Jerry A
Department of Organismic and Evolutionary Biology and the Museum of Comparative Zoology, Harvard University, 26 Oxford Street, Cambridge, Massachusetts 02138, USA.
Evolution. 2007 May;61(5):995-1016. doi: 10.1111/j.1558-5646.2007.00105.x.
An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis-regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis-regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis-regulatory and structural mutations, with a substantial contribution of the latter.
进化发育生物学（“evo devo”）的一个重要原则是，影响形态的适应性突变更有可能发生在基因的顺式调控区域而非蛋白质编码区域。这一观点基于两个主张：（1）顺式调控元件的模块化性质在很大程度上使其免受有害多效性影响；（2）越来越多的经验证据似乎支持基因调控变化在适应性，尤其是形态适应性方面的主要作用。在此我们讨论并批判这些断言。我们首先表明，进化发育生物学关于涉及形态的适应性通过与涉及生理和其他性状不同的遗传机制进化的论点，没有理论或经验依据。此外，某些形式的蛋白质进化可以避免多效性的负面后果，最显著的是通过基因复制。鉴于进化发育生物学的主张，我们接着从全基因组调查和单基因座研究两方面审视了关于适应性遗传基础的大量数据。基因组研究几乎没有支持顺式调控理论：其中许多研究在蛋白质编码区域检测到了适应性，包括转录因子，而很少有研究考察调控区域。转向单基因座研究，我们注意到适应性顺式调控突变最常被引用的例子集中在性状丧失而非获得上，并且尚未有研究精确确定一个进化的调控位点。相比之下，有许多研究既鉴定了结构突变，又从功能上验证了它们对适应性和物种形成的贡献。那么，无论是理论论据还是来自自然界的数据，都不支持进化中顺式调控突变占主导的说法。尽管这一说法可能是正确的，但至少为时过早。适应性和物种形成可能通过顺式调控和结构突变的结合来进行，其中后者起了很大作用。
