McGregor Alistair P, Orgogozo Virginie, Delon Isabelle, Zanet Jennifer, Srinivasan Dayalan G, Payre François, Stern David L
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA.
Nature. 2007 Aug 2;448(7153):587-90. doi: 10.1038/nature05988. Epub 2007 Jul 15.
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 evolution. 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 species. 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 changes. 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.
进化生物学中一个核心且尚未解决的问题是物种内部分离的遗传变异与物种间形态差异的成因之间的关系。经典的新达尔文主义观点假定，物种差异源于多个基因座上小效应变化的积累。然而，许多例子支持发育基因表达中较大的突然变化在形态进化中可能发挥的作用。尽管这一证据可能被视为对新达尔文主义微突变进化观点的挑战，但目前导致物种间形态差异的实际基因的例子很少。在这里，我们研究了果蝇物种间刚毛模式差异的遗传基础，先前已表明这种差异是由单个基因——无毛宝宝（svb）的进化导致的，可能是通过顺式调控变化。我们首先从黑腹果蝇中鉴定出三个不同的svb增强子，它们驱动报告基因以部分重叠的模式表达，共同概括了内源性svb的表达。来自塞舌尔果蝇的所有三个同源增强子都以修饰后的模式驱动表达，其方向与进化后的svb表达模式一致。为了测试这些增强子对实际表型差异的影响，我们进行了种间遗传定位，分辨率足以恢复多个基因内重组体。这种功能分析表明，svb上游与三个已鉴定增强子重叠的独立遗传区域共同作用才能产生塞舌尔果蝇的刚毛模式。我们的结果表明，单个基因座上多个小效应变化的积累是物种间形态差异进化的基础。这些数据支持这样一种观点，即区分物种的大效应等位基因有时可能反映了选定基因上多个小效应突变的积累。
