Qian Wenfeng, Zhang Jianzhi
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Genetics. 2008 Aug;179(4):2319-24. doi: 10.1534/genetics.108.090936. Epub 2008 Aug 9.
The evolutionary process leading to the fixation of newly duplicated genes is not well understood. It was recently proposed that the fixation of duplicate genes is frequently driven by positive selection for increased gene dosage (i.e., the gene dosage hypothesis), because haploinsufficient genes were reported to have more paralogs than haplosufficient genes in the human genome. However, the previous analysis incorrectly assumed that the presence of dominant abnormal alleles of a human gene means that the gene is haploinsufficient, ignoring the fact that many dominant abnormal alleles arise from gain-of-function mutations. Here we show in both humans and yeast that haploinsufficient genes generally do not duplicate more frequently than haplosufficient genes. Yeast haploinsufficient genes do exhibit enhanced retention after whole-genome duplication compared to haplosufficient genes if they encode members of stable protein complexes, but the same phenomenon is absent if the genes do not encode protein complex members, suggesting that the dosage balance effect rather than the dosage effect is the underlying cause of the phenomenon. On the basis of these and other results, we conclude that selection for higher gene dosage does not play a major role in driving the fixation of duplication genes.
导致新复制基因固定的进化过程尚未得到很好的理解。最近有人提出，复制基因的固定通常是由增加基因剂量的正选择驱动的（即基因剂量假说），因为据报道，在人类基因组中，单倍体不足的基因比单倍体充足的基因有更多的旁系同源基因。然而，先前的分析错误地假定人类基因中显性异常等位基因的存在意味着该基因是单倍体不足的，而忽略了许多显性异常等位基因来自功能获得性突变这一事实。在这里，我们在人类和酵母中都表明，单倍体不足的基因通常不会比单倍体充足的基因更频繁地复制。如果酵母单倍体不足的基因编码稳定蛋白质复合物的成员，那么与单倍体充足的基因相比，它们在全基因组复制后确实表现出更高的保留率，但如果这些基因不编码蛋白质复合物成员，则不存在相同的现象，这表明剂量平衡效应而非剂量效应是该现象的根本原因。基于这些以及其他结果，我们得出结论，对更高基因剂量的选择在驱动复制基因的固定过程中并不起主要作用。
