研究背景：发育基因的改变常常导致形态演化，但是，造成演化的突变数量和突变效应却不为人所知。
技术路线： Frankel等人开发出果蝇shavenbaby基因的模型，来研究这一遗传现象。
结果：shavenbaby基因的顺式作用元件出现较多的核苷酸突变，这些突变改变了基因的表达时期和表达水平。这种果蝇要形成无毛的幼虫，需要很多有较小影响的突变（而不是一个有较大影响的突变）。这项研究在单核苷酸突变水平上验证了达尔文支持的渐进性演化观点。
生物探索推荐英文摘要
doi:10.1038/nature10200
Morphological evolution caused by many subtle-effect substitutions in regulatory DNA
Abstract: Morphology evolves often through changes in developmental genes, but the causal mutations, and their effects, remain largely unknown. The evolution of naked cuticle on larvae of Drosophila sechellia resulted from changes in five transcriptional enhancers of shavenbaby (svb), a transcript of the ovo locus that encodes a transcription factor that governs morphogenesis of microtrichiae, hereafter called ‘trichomes’. Here we show that the function of one of these enhancers evolved through multiple single-nucleotide substitutions that altered both the timing and level of svb expression. The consequences of these nucleotide substitutions on larval morphology were quantified with a novel functional assay. We found that each substitution had a relatively small phenotypic effect, and that many nucleotide changes account for this large morphological difference. In addition, we observed that the substitutions had non-additive effects. These data provide unprecedented resolution of the phenotypic effects of substitutions and show how individual nucleotide changes in a transcriptional enhancer have caused morphological
