Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression
Dominance and the evolutionary accumulation of cis- and trans-effects on gene expression
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DOI：
10.1073/pnas.0805160105
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发表时间：
2008-09-23
影响因子：
11.1
通讯作者：
Hartl, Daniel L.
中科院分区：
文献类型：
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作者：
Lemos, Bernardo;Araripe, Luciana O.;Hartl, Daniel L.
基因表达水平似乎处于普遍的稳定选择之下。然而，种群内和种群间丰富的基因表达多样性背后的遗传结构仍然难以捉摸。在这里，我们调查的顺式和反式调节种群内和种群之间的隔离优势的作用。我们使用果蝇染色体替换系表明：（i）>70%的基因在两个纯合系之间的差异表达在杂合系中被掩盖，这表明其中一个替换染色体包含隐性等位基因;（ii）这样大的掩蔽已经用来自相同群体的杂合染色体获得，杂合系中染色体之间的分歧时间对纯合系中观察到的变异的掩盖仅做出小但显著的贡献;（iii）由于隐性和显性等位基因，由反式调节引起的基因表达的变化偏向于与加性的更大偏差，而由于顺式调节的变化显示更高的加性;和（iv）第二染色体之间的遗传分化与增加顺式调节，而反式调节的水平在研究的时间尺度上几乎没有增加。我们的研究结果表明，顺式作用的等位基因可能会优先固定的积极的自然选择，因为他们更高的加性，和破坏基因表达的隐性变异与普遍的反式效应可能是重要的了解种群内的基因表达变异。我们认为隐性低频纯合变异的广泛调节作用可能提供了介导疾病表型和自然群体遗传负荷的一般机制。
Gene expression levels appear to be under pervasive stabilizing selection. Yet the genetic architecture underlying abundant gene expression diversity within and between populations remains elusive. Here, we investigated the role of dominance in the segregation of cis- and trans-regulation within and between populations. We used chromosome substitution lines of Drosophila melanogaster to show that(i) >70% of the genes that are differentially expressed between two homozygous lines are masked in the heterozygous, suggesting that one of the substituted chromosomes contains a recessive allele; (ii) such large masking is already obtained with heterozygous chromosomes originating from the same population, with the time of divergence between chromosomes in heterozygous lines making only a small but significant contribution to the masking of variation observed in homozygous lines; (iii) variation in gene expression due to trans-regulation is biased toward greater deviations from additivity because of recessive and dominant alleles, whereas variation due to cis-regulation shows higher additivity; and (iv) genetic divergence between second chromosomes is associated with increased cis-regulation, whereas the level of trans-regulation shows little increase over the time scale studied. Our results indicate that cis-acting alleles may be preferentially fixed by positive natural selection because of their higher additivity, and that the disruption of gene expression by recessive variation with pervasive trans-effects may be important for understanding gene expression variation within populations. We suggest that widespread regulatory effects of recessive low-frequency homozygous variation may provide a general mechanism mediating disease phenotypes and the genetic load of natural populations.