Institute of Population Genetics, Veterinärmedizinische Universität Wien, Vienna, Austria.
Institute of Animal Breeding and Genetics, Veterinärmedizinische Universität Wien, Vienna, Austria.
J Evol Biol. 2012 Oct;25(10):1975-1990. doi: 10.1111/j.1420-9101.2012.02580.x. Epub 2012 Aug 20.
An unconstrained reference sequence facilitates the detection of selection. In Drosophila, sequence variation in short introns seems to be least influenced by selection and dominated by mutation and drift. Here, we test this with genome-wide sequences using an African population (Malawi) of D. melanogaster and data from the related outgroup species D. simulans, D. sechellia, D. erecta and D. yakuba. The distribution of mutations deviates from equilibrium, and the content of A and T (AT) nucleotides shows an excess of variance among introns. We explain this by a complex mutational pattern: a shift in mutational bias towards AT, leading to a slight nonequilibrium in base composition and context-dependent mutation rates, with G or C (GC) sites mutating most frequently in AT-rich introns. By comparing the corresponding allele frequency spectra of AT-rich vs. GC-rich introns, we can rule out the influence of directional selection or biased gene conversion on the mutational pattern. Compared with neutral equilibrium expectations, polymorphism spectra show an excess of low frequency and a paucity of intermediate frequency variants, irrespective of the direction of mutation. Combining the information from different outgroups with the polymorphism data and using a generalized linear model, we find evidence for shared ancestral polymorphism between D. melanogaster and D. simulans, D. sechellia, arguing against a bottleneck in D. melanogaster. Generally, we find that short introns can be used as a neutral reference on a genome-wide level, if the spatially and temporally varying mutational pattern is accounted for.
无约束的参考序列有助于检测选择。在果蝇中，短内含子的序列变异似乎受选择的影响最小，而主要受突变和漂变的影响。在这里，我们使用来自非洲（马拉维）的 D. melanogaster 基因组和相关的外群物种 D. simulans、D. sechellia、D. erecta 和 D. yakuba 的数据，通过全基因组序列对此进行了测试。突变的分布偏离了平衡，A 和 T（AT）核苷酸的含量在内含子之间表现出过多的方差。我们通过复杂的突变模式来解释这一点：突变偏向 AT 的偏向发生变化，导致碱基组成和上下文相关突变率的轻微不平衡，在富含 AT 的内含子中，G 或 C（GC）位点最常发生突变。通过比较富含 AT 的内含子与富含 GC 的内含子的相应等位基因频率谱，我们可以排除定向选择或偏向基因转换对突变模式的影响。与中性平衡预期相比，多态性谱显示低频变体过多，中频变体不足，无论突变的方向如何。将来自不同外群的信息与多态性数据相结合，并使用广义线性模型，我们发现了 D. melanogaster 和 D. simulans、D. sechellia 之间存在共同祖先多态性的证据，这与 D. melanogaster 的瓶颈相反。一般来说，如果考虑到空间和时间上变化的突变模式，短内含子可以作为全基因组水平的中性参考。
