Zapata Carlos, Núñez Concepción, Velasco Teresa
Departamento de Genética, Universidad de Santiago, 15782 Santiago de Compostela, Spain.
Genetics. 2002 Aug;161(4):1539-50. doi: 10.1093/genetics/161.4.1539.
The within-chromosome distribution of gametic disequilibrium (GD) between protein loci, and the underlying evolutionary factors of this distribution, are still largely unknown. Here, we report a detailed study of GD between a large number of protein loci (15) spanning 87% of the total length of the third chromosome of Drosophila melanogaster in a large sample of haplotypes (600) drawn from a single natural population. We used a sign-based GD estimation method recently developed for multiallelic systems, which considerably increases both the statistical power and the accuracy of estimation of the intensity of GD. We found that strong GD between pairs of protein loci was widespread throughout the chromosome. In total, 22% of both the pairs of alleles and pairs of loci were in significant GD, with mean intensities (as measured by D' coefficients) of 0.43 and 0.31, respectively. In addition, strong GD often occurs between loci that are far apart. By way of illustration, 32% of the allele pairs in significant GD occurred within pairs of loci separated by effective frequencies of recombination (EFRs) of 15-20 cM, the mean D' value being 0.49. These observations are in sharp contrast with previous studies showing that GD between protein loci is rarely found in natural populations of outcrossing species, even between very closely linked loci. Interestingly, we found that most instances of significant interallelic GD (68%) involved functionally related protein loci. Specifically, GD was markedly more frequent between protein loci related by the functions of hormonal control, molybdenum control, antioxidant defense system, and reproduction than between loci without known functional relationship, which is indicative of epistatic selection. Furthermore, long-distance GD between functionally related loci (mean EFR 9 cM) suggests that epistatic interactions must be very strong along the chromosome. This evidence is hardly compatible with the neutral theory and has far-reaching implications for understanding the multilocus architecture of the functional genome. Our findings also suggest that GD may be a useful tool for discovering networks of functionally interacting proteins.
蛋白质基因座之间配子不平衡（GD）在染色体内部的分布情况，以及这种分布背后的进化因素，目前仍很大程度上未知。在此，我们报告了一项详细研究，该研究针对从单个自然种群中抽取的大量单倍型样本（600个），研究了果蝇黑腹果蝇第三条染色体全长87%范围内的大量蛋白质基因座（15个）之间的GD。我们使用了一种最近为多等位基因系统开发的基于符号的GD估计方法，该方法显著提高了统计功效以及GD强度估计的准确性。我们发现，蛋白质基因座对之间的强GD在整个染色体上广泛存在。总共，22%的等位基因对和基因座对处于显著的GD中，平均强度（以D'系数衡量）分别为0.43和0.31。此外，强GD经常出现在距离较远的基因座之间。举例来说，处于显著GD中的等位基因对有32%出现在有效重组频率（EFR）为15 - 20厘摩的基因座对之间，平均D'值为0.49。这些观察结果与之前的研究形成鲜明对比，之前的研究表明，在异交物种的自然种群中，很少发现蛋白质基因座之间的GD，即使是在紧密连锁的基因座之间。有趣的是，我们发现大多数显著的等位基因间GD实例（68%）涉及功能相关的蛋白质基因座。具体而言，与激素控制、钼控制、抗氧化防御系统和繁殖功能相关的蛋白质基因座之间的GD明显比没有已知功能关系的基因座之间更频繁，这表明存在上位性选择。此外，功能相关基因座之间的长距离GD（平均EFR为9厘摩）表明，沿染色体的上位性相互作用一定非常强。这一证据很难与中性理论相契合，对于理解功能基因组的多位点结构具有深远意义。我们的研究结果还表明，GD可能是发现功能相互作用蛋白质网络的有用工具。
