Population growth inflates the per-individual number of deleterious mutations and reduces their mean effect.
Population growth inflates the per-individual number of deleterious mutations and reduces their mean effect.
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DOI：
10.1534/genetics.113.153973
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发表时间：
2013-11
期刊：
影响因子：
3.3
通讯作者：
Keinan A
中科院分区：
文献类型：
--
作者：
Gazave E;Chang D;Clark AG;Keinan A
这项研究解决了净化选择在最近的人口快速增长中是如何运作的问题，比如人类人口所经历的。这不是一个直截了当的问题，因为人类种群并不处于平衡状态：种群遗传学预测，一方面，自然选择的效力随着种群规模的增加而增加，消除了更弱的有害变异；另一方面，大量的有害突变将被引入种群，并且随着种群的增长，它们的拷贝数量更有可能增加。为了了解自然选择和人口增长的相互作用如何塑造人类遗传变异的模式，我们使用计算机模拟研究了具有不同选择系数的突变轨迹。我们观察到，虽然种群增长显著增加了种群中有害分离位点的数量，但它只轻微增加了每个个体携带的数量。我们的模拟还显示了自然选择的效率提高，反映在每一代消除的有害突变的更高比例和更有效地消除最有害的突变。因此，虽然在没有生长的情况下，每个个体携带的有害等位基因数量比预期的要多，但每个分离等位基因的平均选择系数却较小。综上所述，我们的研究结果表明，在不断增长的人群中，复杂疾病的遗传风险可能分布在大量毒性更弱的罕见变异上。
This study addresses the question of how purifying selection operates during recent rapid population growth such as has been experienced by human populations. This is not a straightforward problem because the human population is not at equilibrium: population genetics predicts that, on the one hand, the efficacy of natural selection increases as population size increases, eliminating ever more weakly deleterious variants; on the other hand, a larger number of deleterious mutations will be introduced into the population and will be more likely to increase in their number of copies as the population grows. To understand how patterns of human genetic variation have been shaped by the interaction of natural selection and population growth, we examined the trajectories of mutations with varying selection coefficients, using computer simulations. We observed that while population growth dramatically increases the number of deleterious segregating sites in the population, it only mildly increases the number carried by each individual. Our simulations also show an increased efficacy of natural selection, reflected in a higher fraction of deleterious mutations eliminated at each generation and a more efficient elimination of the most deleterious ones. As a consequence, while each individual carries a larger number of deleterious alleles than expected in the absence of growth, the average selection coefficient of each segregating allele is less deleterious. Combined, our results suggest that the genetic risk of complex diseases in growing populations might be distributed across a larger number of more weakly deleterious rare variants.
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影响因子：
5.8
作者：
Hernandez, Ryan D.
通讯作者：
Hernandez, Ryan D.
影响因子：
9.8
作者：
Gusev, Alexander;Kenny, Eimear E.;Pe'er, Itsik
通讯作者：
Pe'er, Itsik
DOI：
10.1126/science.1217283
发表时间：
2012-05-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Keinan A;Clark AG
通讯作者：
Clark AG
影响因子：
3.3
作者：
Fernández, B;García-Dorado, A;Caballero, A
通讯作者：
Caballero, A
DOI：
10.1101/sqb.1955.020.01.006
发表时间：
1955-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
KIMURA, M
通讯作者：
KIMURA, M