Genetic complexity and quantitative trait loci mapping of yeast morphological traits.
Genetic complexity and quantitative trait loci mapping of yeast morphological traits.
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DOI：
10.1371/journal.pgen.0030031
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发表时间：
2007-02-23
期刊：
影响因子：
4.5
通讯作者：
Yvert G
中科院分区：
文献类型：
--
作者：
Nogami S;Ohya Y;Yvert G
功能基因组学依赖于两个基本参数：表型测量的灵敏度和检测导致表型变异的基因组扰动的能力。在模式生物中，两种类型的扰动被广泛使用。人工突变可以引入几乎任何基因，并允许通过突变体适应性系统分析基因功能。或者，天然遗传变异可以通过遗传作图与特定表型相关联。然而，模式生物提供的基因组操作和育种的机会有时会被表型限制所抵消。在这里，我们研究了自然的遗传多样性的酿酒酵母细胞形态使用一个非常敏感的高通量成像平台。我们从两个野生型相异背景之间的交叉中量化了超过50，000个酵母细胞中的501个形态学参数。广泛的形态差异，发现这些背景之间。这些性状的遗传结构复杂，既有上位性遗传，也有超亲分离。我们定位了67个性状的数量性状位点（QTL），发现了364个性状分离和基因表达水平遗传之间的相关性。我们通过替换基因组中的单个碱基来验证一个QTL。这项研究说明了天然酵母菌株之间的细胞性状的天然多样性和复杂性，并为多性状的遗传基因组学解剖提供了一个理想的框架。我们的研究结果没有重叠与以前获得的结果从系统性缺失菌株，表明这两种方法是必要的基因组的功能探索。熟悉的面孔或狗的品种很容易识别，因为个体的形态根据其遗传背景而不同。对于单细胞生物，形态学简化为细胞特征的形状和大小。微生物学家注意到S.酿酒酵母细胞（面包酵母）在不同菌株之间存在差异，但这些差异通常被定性描述。我们使用高通量成像平台来研究酵母细胞分裂时的形态。用三种荧光染料对细胞进行染色，这样就可以识别它们的外周、DNA和肌动蛋白，并通过专门的软件程序分析它们的图像。在两个远缘菌株之间发现了许多形态学差异。啤酒。通过杂交这两个菌株，我们进行了数量遗传学：在基因组上发现了几个控制形态变异的位点，并在基因表达和形态变化之间建立了相关性。使用生物信息学，我们表明，所获得的结果不重叠，从酵母细胞中的特定基因被删除的先前获得的结果。因此，这项研究说明了诱变和自然遗传变异的使用如何提供互补知识。
Functional genomics relies on two essential parameters: the sensitivity of phenotypic measures and the power to detect genomic perturbations that cause phenotypic variations. In model organisms, two types of perturbations are widely used. Artificial mutations can be introduced in virtually any gene and allow the systematic analysis of gene function via mutants fitness. Alternatively, natural genetic variations can be associated to particular phenotypes via genetic mapping. However, the access to genome manipulation and breeding provided by model organisms is sometimes counterbalanced by phenotyping limitations. Here we investigated the natural genetic diversity of Saccharomyces cerevisiae cellular morphology using a very sensitive high-throughput imaging platform. We quantified 501 morphological parameters in over 50,000 yeast cells from a cross between two wild-type divergent backgrounds. Extensive morphological differences were found between these backgrounds. The genetic architecture of the traits was complex, with evidence of both epistasis and transgressive segregation. We mapped quantitative trait loci (QTL) for 67 traits and discovered 364 correlations between traits segregation and inheritance of gene expression levels. We validated one QTL by the replacement of a single base in the genome. This study illustrates the natural diversity and complexity of cellular traits among natural yeast strains and provides an ideal framework for a genetical genomics dissection of multiple traits. Our results did not overlap with results previously obtained from systematic deletion strains, showing that both approaches are necessary for the functional exploration of genomes. A familiar face or a dog breed is easily recognized because morphology of individuals differs according to their genetic backgrounds. For single-cell organisms, morphology reduces to the shape and size of cellular features. Microbiologists noticed that the shape of S. cerevisiae cells (baker's yeast) differs from one strain to another, but these differences were usually described qualitatively. We used a high-throughput imaging platform to study the morphology of yeast cells when they divide. Cells were stained with three fluorescent dyes so that their periphery, their DNA, and their actin could be recognized, and their images were analysed by a specialized software program. Numerous morphological differences were found between two distant strains of S. cerevisiae. By crossing these two strains, we performed quantitative genetics: several loci controlling morphological variations were found on the genome, and correlations were made between gene expression and morphology changes. Using bioinformatics, we showed that the results obtained do not overlap with previous results obtained from yeast cells in which specific genes are deleted. The study, therefore, illustrates how mutagenesis and the use of natural genetic variations provide complementary knowledge.
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