Steinmetz Lars M, Sinha Himanshu, Richards Dan R, Spiegelman Jamie I, Oefner Peter J, McCusker John H, Davis Ronald W
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature. 2002 Mar 21;416(6878):326-30. doi: 10.1038/416326a.
Most phenotypic diversity in natural populations is characterized by differences in degree rather than in kind. Identification of the actual genes underlying these quantitative traits has proved difficult. As a result, little is known about their genetic architecture. The failures are thought to be due to the different contributions of many underlying genes to the phenotype and the ability of different combinations of genes and environmental factors to produce similar phenotypes. This study combined genome-wide mapping and a new genetic technique named reciprocal-hemizygosity analysis to achieve the complete dissection of a quantitative trait locus (QTL) in Saccharomyces cerevisiae. A QTL architecture was uncovered that was more complex than expected. Functional linkages both in cis and in trans were found between three tightly linked quantitative trait genes that are neither necessary nor sufficient in isolation. This arrangement of alleles explains heterosis (hybrid vigour), the increased fitness of the heterozygote compared with homozygotes. It also demonstrates a deficiency in current approaches to QTL dissection with implications extending to traits in other organisms, including human genetic diseases.
自然种群中的大多数表型多样性的特征在于程度上的差异而非种类上的差异。已证明确定这些数量性状背后的实际基因颇具难度。因此，人们对其遗传结构知之甚少。这些失败被认为是由于许多潜在基因对表型的不同贡献以及基因与环境因素的不同组合产生相似表型的能力所致。本研究结合全基因组定位和一种名为相互半合子分析的新遗传技术，实现了对酿酒酵母中一个数量性状基因座（QTL）的完整剖析。发现了一种比预期更复杂的QTL结构。在三个紧密连锁的数量性状基因之间发现了顺式和反式的功能联系，这些基因单独存在时既非必需也不充分。这种等位基因的排列解释了杂种优势（杂交活力），即杂合子相对于纯合子的适应性增强。它还证明了当前QTL剖析方法的不足，其影响延伸到包括人类遗传疾病在内的其他生物体的性状。
