自然界中有机生命体形态和大小的多样性分异究竟如何而来？科学家通过对果蝇进行研究解开了谜团：果蝇体内一种基因强化因子通过逐步改变DNA序列来增加生物形貌分异度。

图：背部缺少毛发群的Drosophila sechellia

基因转录过程被严密控制，一系列错综复杂的DNA调控序列、数量巨大的蛋白质与其他各种因素共同影响着基因的激活与作用。这一过程的研究曾令无数分子生物学家困惑。不过现在，来自美国普林斯顿大学的D.Stern，斯洛伐克兽医大学的A.McGregor和法国图卢兹大学的François Payre的共同研究，开启了此项研究的新篇章。

研究对象为两种果蝇的幼虫，分别是Drosophila melanogaster和Drosophila sechellia，前者为广泛分布的属种，后者则仅分布于塞舌尔，两者以毛状体（trichomes）的不同区分。这种区别源自名为“光宝贝”（shaven baby, svb）的基因，光宝贝基因的不表达使得Drosophila sechellia幼虫的头部和背部缺少毛发群。McGregor更进一步发现，E强化因子对光宝贝基因的表达与否起着决定作用，其中的E6段承担着激活光宝贝基因的任务，而Drosophila sechellia的E6段与众不同。

Stern手下的两名博士后系统检测了E强化因子各种变化的影响。结果显示，E强化因子至少有五种对表达结果产生影响的变化，它们其中的任何一个都仅能产生微弱的影响，但五种变化组合到一起，则会产生巨大的影响。因此，五种变化之间的任意组合，都会产生形貌不同的果蝇种类。研究结果对于理解形貌进化有重要的指示意义。

原文出处：

Nature   DOI：10.1038/nature05988

Morphological evolution through multiple cis-regulatory mutations at a single gene

Alistair P. McGregor, Virginie Orgogozo, Isabelle Delon, Jennifer Zanet, Dayalan G. Srinivasan, Franois Payre & David L. Stern

One central, and yet unsolved, question in evolutionary biology is the relationship between the genetic variants segregating within species and the causes of morphological differences between species. The classic neo-darwinian view postulates that species differences result from the accumulation of small-effect changes at multiple loci. However, many examples support the possible role of larger abrupt changes in the expression of developmental genes in morphological evolution1, 2, 3. Although this evidence might be considered a challenge to a neo-darwinian micromutationist view of evolution, there are currently few examples of the actual genes causing morphological differences between species4, 5, 6, 7, 8, 9, 10. Here we examine the genetic basis of a trichome pattern difference between Drosophila species, previously shown to result from the evolution of a single gene, shavenbaby (svb), probably through cis-regulatory changes6. We first identified three distinct svb enhancers from D. melanogaster driving reporter gene expression in partly overlapping patterns that together recapitulate endogenous svb expression. All three homologous enhancers from D. sechellia drive expression in modified patterns, in a direction consistent with the evolved svb expression pattern. To test the influence of these enhancers on the actual phenotypic difference, we conducted interspecific genetic mapping at a resolution sufficient to recover multiple intragenic recombinants. This functional analysis revealed that independent genetic regions upstream of svb that overlap the three identified enhancers are collectively required to generate the D. sechellia trichome pattern. Our results demonstrate that the accumulation of multiple small-effect changes at a single locus underlies the evolution of a morphological difference between species. These data support the view that alleles of large effect that distinguish species may sometimes reflect the accumulation of multiple mutations of small effect at select genes.