Evolutionary Genetic Signatures of Selection on Bone-Related Variation within Human and Chimpanzee Populations.
Evolutionary Genetic Signatures of Selection on Bone-Related Variation within Human and Chimpanzee Populations.
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DOI：
10.3390/genes13020183
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发表时间：
2022-01-21
期刊：
影响因子：
3.5
通讯作者：
Verrelli BC
中科院分区：
文献类型：
--
作者：
Stover DA;Housman G;Stone AC;Rosenberg MS;Verrelli BC
不同人群的骨强度以及骨骼疾病的发生率和严重程度存在显着差异，部分原因在于潜在的遗传差异。虽然临床模型预测这种变异在很大程度上是有害的，但与疾病无关的自然种群变异可能会被忽视，从而改变我们对自然选择如何在近代和近期时期塑造骨骼形态的看法。在这里，我们对人类和黑猩猩自然群体的临床数据集和千人基因组计划数据集中的主要骨结构蛋白基因 I 型胶原蛋白 α 1 (COL1A1) 进行了首次基于群体的遗传比较分析。与临床研究的预测相反，我们揭示了丰富的 COL1A1 氨基酸变异，预计与自然群体中的疾病关系不大。我们还在人类和黑猩猩已知基因表达调控区域中发现了与内含子单倍型结构、连锁不平衡和群体分化相关的正选择特征。这些结果让人回想起最近和深层的进化机制是如何联系起来的，因为在 4.5 亿年的进化过程中，脊椎动物之间形成的骨形态差异是对随着时间的推移在种群内分离的微妙 I 型胶原蛋白功能变异进行积极选择的结果。
Bone strength and the incidence and severity of skeletal disorders vary significantly among human populations, due in part to underlying genetic differentiation. While clinical models predict that this variation is largely deleterious, natural population variation unrelated to disease can go unnoticed, altering our perception of how natural selection has shaped bone morphologies over deep and recent time periods. Here, we conduct the first comparative population-based genetic analysis of the main bone structural protein gene, collagen type I α 1 (COL1A1), in clinical and 1000 Genomes Project datasets in humans, and in natural populations of chimpanzees. Contrary to predictions from clinical studies, we reveal abundant COL1A1 amino acid variation, predicted to have little association with disease in the natural population. We also find signatures of positive selection associated with intron haplotype structure, linkage disequilibrium, and population differentiation in regions of known gene expression regulation in humans and chimpanzees. These results recall how recent and deep evolutionary regimes can be linked, in that bone morphology differences that developed among vertebrates over 450 million years of evolution are the result of positive selection on subtle type I collagen functional variation segregating within populations over time.
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影响因子：
10.7
作者：
Fischer, A;Wiebe, V;Przeworski, M
通讯作者：
Przeworski, M
影响因子：
14.9
作者：
Dalgleish, R
通讯作者：
Dalgleish, R
影响因子：
4.4
作者：
Chan, Ting-Fung;Poon, Annie;Kwok, Pui-Yan
通讯作者：
Kwok, Pui-Yan
影响因子：
4.1
作者：
Black, A;Tilmont, EM;Lane, MA
通讯作者：
Lane, MA
DOI：
10.1073/pnas.84.24.8869
发表时间：
1987-12-01
影响因子：
11.1
作者：
BORNSTEIN, P;MCKAY, J;GELINAS, RE
通讯作者：
GELINAS, RE