Fox Aleah K, Tuch Brian B, Chuang Jeffrey H
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
BMC Evol Biol. 2008 Jun 27;8:186. doi: 10.1186/1471-2148-8-186.
The patterns of mutation vary both within and across genomes. It has been shown for a few mammals that mutation rates vary within the genome, while for unknown reasons, the sensu stricto yeasts have uniform rates instead. The generality of these observations has been unknown. Here we examine silent site substitutions in a more expansive set (20 mammals, 27 fungi, 4 insects) to determine why some genomes demonstrate this mosaic distribution and why others are uniform.
We applied several intragene and intergene correlation tests to measure regional substitution patterns. Assuming that silent sites are a reasonable approximation to neutrally mutating sequence, our results show that all multicellular eukaryotes exhibit mutational heterogeneity. In striking contrast, all fungi are mutationally uniform - with the exception of three Candida species: C. albicans, C. dubliniensis, and C. tropicalis. We speculate that aspects of replication timing may be responsible for distinguishing these species. Our analysis also reveals classes of genes whose silent sites behave anomalously with respect to the mutational background in many species, indicating prevalent selective pressures. Genes associated with nucleotide binding or gene regulation have consistently low silent substitution rates in every mammalian species, as well as multiple fungi. On the other hand, receptor genes repeatedly exhibit high silent substitution rates, suggesting they have been influenced by diversifying selection.
Our findings provide a framework for understanding the regional mutational properties of eukaryotes, revealing a sharp difference between fungi and multicellular species. They also elucidate common selective pressures acting on eukaryotic silent sites, with frequent evidence for both purifying and diversifying selection.
突变模式在基因组内部和不同基因组之间均存在差异。对于一些哺乳动物而言，已表明基因组内的突变率存在差异，而出于未知原因，严格意义上的酵母具有均匀的突变率。这些观察结果的普遍性尚不清楚。在此，我们研究了范围更广的一组物种（20种哺乳动物、27种真菌、4种昆虫）中的沉默位点替换情况，以确定为何一些基因组呈现这种镶嵌分布，而另一些则是均匀分布。
我们应用了几种基因内和基因间相关性测试来测量区域替换模式。假设沉默位点是对中性突变序列的合理近似，我们的结果表明，所有多细胞真核生物都表现出突变异质性。与之形成鲜明对比的是，所有真菌在突变方面都是均匀的——除了三种念珠菌属物种：白色念珠菌、都柏林念珠菌和热带念珠菌。我们推测复制时间的某些方面可能是区分这些物种的原因。我们的分析还揭示了在许多物种中，其沉默位点相对于突变背景表现异常的基因类别，这表明存在普遍的选择压力。在每个哺乳动物物种以及多种真菌中，与核苷酸结合或基因调控相关的基因始终具有较低的沉默替换率。另一方面，受体基因反复表现出较高的沉默替换率，这表明它们受到了多样化选择的影响。
我们的研究结果为理解真核生物的区域突变特性提供了一个框架，揭示了真菌与多细胞物种之间的显著差异。它们还阐明了作用于真核生物沉默位点的常见选择压力，同时有大量证据表明存在纯化选择和多样化选择。
