Dosage sensitivity and the evolution of gene families in yeast

Dosage sensitivity and the evolution of gene families in yeast
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DOI:
10.1038/nature01771
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发表时间:
2003-07-10
期刊:
影响因子:
64.8
通讯作者:
Hurst, LD
Hurst, LD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Papp, B;Pál, C;Hurst, LD

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根据我们所说的平衡假说,蛋白质-蛋白质复合物的亚组分浓度不平衡可能是有害的(1)。如果是这样的话,有两个后果:首先,蛋白质复合物亚基的过表达和过表达都会降低适应度,其次,亚基转录共调节的准确性应该反映不平衡的有害后果。在这里,我们证明所有这些预测都在酵母(Saccharomyces cerevisiae)中维持。这支持了一个假设(2,3),即显性是生理和代谢的副产品,而不是为了掩盖突变的有害影响而选择的结果。除此之外,蛋白质亚基的单基因复制被认为是有害的,因为这也会导致不平衡。正如预期的那样,我们发现大基因家族的成员很少参与复合体。因此,平衡假说为理解显性和基因家族大小的组成部分提供了一个单一的理论框架。
According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein - protein complex can be deleterious(1). If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast ( Saccharomyces cerevisiae). This supports the hypothesis(2,3) that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.