The Saccharomyces cerevisiae W303-K6001 cross-platform genome sequence: insights into ancestry and physiology of a laboratory mutt.

The Saccharomyces cerevisiae W303-K6001 cross-platform genome sequence: insights into ancestry and physiology of a laboratory mutt.
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DOI:
10.1098/rsob.120093
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发表时间:
2012-08
期刊:
影响因子:
5.8
通讯作者:
Timmermann B
Timmermann B
中科院分区:
生物学2区
文献类型:
--
作者:
Ralser M;Kuhl H;Ralser M;Werber M;Lehrach H;Breitenbach M;Timmermann B

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酿酒酵母(Saccharomyces cerevisiae)菌株W303是一种应用广泛的模式生物。然而,人们对它的遗传起源知之甚少,因为它是在20世纪70年代由不确定谱系的酵母菌株杂交而成的。为了深入了解它的祖先和生理,我们对它的变体W303-K6001的基因组进行了测序,W303-K6001是衰老研究的酵母模型。两种下一代测序技术(Illumina和Roche/454测序)的结合产生了11.8 Mb的基因组组装,N50 contig长度为262 kb。尽管测序比全基因组平铺阵列更加精确和敏感,但两种NGS平台都产生了许多假阳性结果。在378倍的平均覆盖率下,两种技术仅确认了S288c参考基因组差异的74%。共识的W303-K6001基因组与S288c有8133个位置的差异,预测799个蛋白质的氨基酸序列改变,包括衰老和抗逆性因素。W303-K6001(85.4%)基因组与S288c几乎相同(小于等于每kb 0.5个变异),因此起源于同一祖先。非s288c区域在基因组中的分布不均匀,XVI染色体与s288c相似度最高(99.6%),XI染色体与s288c相似度最低(54.5%)。其中几个集群与Σ1278B(另一个广泛使用的s288c相关模型)共享,表明这些菌株共享第二个祖先。因此,W303-K6001基因组描绘了模型菌株之间复杂遗传关系的细节,这些关系可以追溯到实验酵母遗传学的早期。此外,本研究强调了将多种NGS和基因组组装技术相结合以实现基因组研究中准确的变异召唤的必要性。
Saccharomyces cerevisiae strain W303 is a widely used model organism. However, little is known about its genetic origins, as it was created in the 1970s from crossing yeast strains of uncertain genealogy. To obtain insights into its ancestry and physiology, we sequenced the genome of its variant W303-K6001, a yeast model of ageing research. The combination of two next-generation sequencing (NGS) technologies (Illumina and Roche/454 sequencing) yielded an 11.8 Mb genome assembly at an N50 contig length of 262 kb. Although sequencing was substantially more precise and sensitive than whole-genome tiling arrays, both NGS platforms produced a number of false positives. At a 378× average coverage, only 74 per cent of called differences to the S288c reference genome were confirmed by both techniques. The consensus W303-K6001 genome differs in 8133 positions from S288c, predicting altered amino acid sequence in 799 proteins, including factors of ageing and stress resistance. The W303-K6001 (85.4%) genome is virtually identical (less than equal to 0.5 variations per kb) to S288c, and thus originates in the same ancestor. Non-S288c regions distribute unequally over the genome, with chromosome XVI the most (99.6%) and chromosome XI the least (54.5%) S288c-like. Several of these clusters are shared with Σ1278B, another widely used S288c-related model, indicating that these strains share a second ancestor. Thus, the W303-K6001 genome pictures details of complex genetic relationships between the model strains that date back to the early days of experimental yeast genetics. Moreover, this study underlines the necessity of combining multiple NGS and genome-assembling techniques for achieving accurate variant calling in genomic studies.
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发表时间: 2003-09-02
影响因子: 11.1
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发表时间: 1995-08-01
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