Andolfatto Peter
Section of Ecology, Behavior and Evolution, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
Nature. 2005 Oct 20;437(7062):1149-52. doi: 10.1038/nature04107.
A large fraction of eukaryotic genomes consists of DNA that is not translated into protein sequence, and little is known about its functional significance. Here I show that several classes of non-coding DNA in Drosophila are evolving considerably slower than synonymous sites, and yet show an excess of between-species divergence relative to polymorphism when compared with synonymous sites. The former is a hallmark of selective constraint, but the latter is a signature of adaptive evolution, resembling general patterns of protein evolution in Drosophila. I estimate that about 40-70% of nucleotides in intergenic regions, untranslated portions of mature mRNAs (UTRs) and most intronic DNA are evolutionarily constrained relative to synonymous sites. However, I also use an extension to the McDonald-Kreitman test to show that a substantial fraction of the nucleotide divergence in these regions was driven to fixation by positive selection (about 20% for most intronic and intergenic DNA, and 60% for UTRs). On the basis of these observations, I suggest that a large fraction of the non-translated genome is functionally important and subject to both purifying selection and adaptive evolution. These results imply that, although positive selection is clearly an important facet of protein evolution, adaptive changes to non-coding DNA might have been considerably more common in the evolution of D. melanogaster.
大部分真核生物基因组由不被翻译成蛋白质序列的DNA组成，人们对其功能意义知之甚少。在此我表明，果蝇中几类非编码DNA的进化速度比同义位点慢得多，但与同义位点相比，种间差异相对于多态性却过多。前者是选择约束的标志，而后者是适应性进化的特征，类似于果蝇中蛋白质进化的一般模式。我估计，相对于同义位点，基因间区域、成熟mRNA的非翻译部分（UTR）和大多数内含子DNA中约40 - 70%的核苷酸在进化上受到约束。然而，我还使用了对麦克唐纳 - 克里特曼检验的扩展来表明，这些区域中相当一部分核苷酸差异是由正选择驱动而固定下来的（大多数内含子和基因间DNA约为20%，UTR为60%）。基于这些观察结果，我认为大部分非翻译基因组在功能上很重要，并且受到纯化选择和适应性进化的双重影响。这些结果意味着，虽然正选择显然是蛋白质进化的一个重要方面，但在黑腹果蝇的进化过程中，非编码DNA的适应性变化可能更为普遍。
