Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci.
Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci.
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DOI：
10.1016/j.gene.2008.07.020
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发表时间：
2009-07-15
期刊：
影响因子：
3.5
通讯作者：
Thorne, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Choi, Sang Chul;Stone, Eric A.;Kishino, Hirohisa;Thorne, Jeffrey L.
我们认为，当两个等位基因有一个单一的非同义的差异，当自然选择通过蛋白质的三级结构的行为是祖先的推断。在中性条件下，一个等位基因是祖先的概率等于它的频率，而在选择条件下，这个概率取决于等位基因的频率以及选择压力的大小和方向。虽然等位基因频率可以很好地估计从种内数据，小的健身差异有很大的进化影响，但可能难以估计只有种内数据。用于从基因型预测表型方面的方法可以补充种内序列数据。最近发展的统计技术可以评估表型的影响，如蛋白质三级结构对分子进化的影响。虽然这些技术最初被设计用于比较来自不同物种的蛋白质编码基因，但由此产生的种间推断可以被分配到种群遗传解释中，以评估选择压力的影响，我们在这里使用它们沿着种内等位基因频率数据来估计等位基因是祖先的概率。我们专注于140个非同义的单核苷酸多态性的人类是在蛋白质与已知的三级结构。我们发现，我们的技术采用蛋白质三级结构信息产生一些生物学上合理的结果，但它并没有实质性地改善祖先人类等位基因类型的推断。
We consider the inference of which of two alleles is ancestral when the alleles have a single nonsynonymous difference and when natural selection acts via protein tertiary structure. Whereas the probability that an allele is ancestral under neutrality is equal to its frequency, under selection this probability depends on allele frequency and on the magnitude and direction of selection pressure. Although allele frequencies can be well estimated from intraspecific data, small fitness differences have a large evolutionary impact but can be difficult to estimate with only intraspecific data. Methods for predicting aspects of phenotype from genotype can supplement intraspecific sequence data. Recently developed statistical techniques can assess effects of phenotypes, such as protein tertiary structure on molecular evolution. While these techniques were initially designed for comparing protein-coding genes from different species, the resulting interspecific inferences can be assigned population genetic interpretations to assess the effect of selection pressure, and we use them here along with intraspecific allele frequency data to estimate the probability that an allele is ancestral. We focus on 140 nonsynonymous single nucleotide polymorphisms of humans that are in proteins with known tertiary structures. We find that our technique for employing protein tertiary structure information yields some biologically plausible results but that it does not substantially improve the inference of ancestral human allele types.
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DOI：
10.1073/pnas.2536718100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Hughes, AL;Packer, B;Yeager, M
通讯作者：
Yeager, M
影响因子：
1.4
作者：
Krone, SM;Neuhauser, C
通讯作者：
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影响因子：
5.8
作者：
Krishnan, VG;Westhead, DR
通讯作者：
Westhead, DR
影响因子：
7
作者：
Giardine, B;Riemer, C;Nekrutenko, A
通讯作者：
Nekrutenko, A
影响因子：
8
作者：
FLORES, TP;ORENGO, CA;THORNTON, JM
通讯作者：
THORNTON, JM