Highly complete long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity.
Highly complete long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity.
复制标题
DOI：
10.1101/gr.277515.122
复制
发表时间：
2023-05
期刊：
影响因子：
7
通讯作者：
Sadhu, Meru J.
中科院分区：
文献类型：
--
作者：
Weller, Cory A.;Andreev, Ilya;Chambers, Michael J.;Park, Morgan;Bloom, Joshua S.;Sadhu, Meru J.
了解性状变异的遗传原因是遗传学研究的主要目标。个体遗传差异的一种方式是通过可变的泛体基因：即只存在于种群中某些个体的基因。完整基因的存在或缺失可能会对性状变异产生很大影响。然而，由于依赖于将短读测序与参考基因组进行比对，在标准的基因分型工作流程中可能会遗漏可变的泛基因组基因。研究性状变异的遗传基础的一种流行方法是连锁作图，它识别数量性状基因座(QTL)，即基因组中含有致病遗传变异的区域。在发芽酵母的大规模连锁图谱中发现了数千个影响无数酵母表型的QTL。为了能够解析由可变的泛基因组基因引起的QTL，我们使用长读测序的方法来产生16个不同酵母分离物的高度完整的从头开始基因组组合。利用这些组件，我们将麦芽糖、蔗糖、棉子糖和氧化应激上的生长QTL解析到特定的基因，这些基因在参考基因组中缺失，但在更广泛的酵母种群中以相当高的频率存在。基因的拷贝也复制到参考基因组中不存在的染色体上，我们发现这些拷贝产生了额外的QTL，其分辨率需要pangenome特征。我们的发现表明，需要高度完整的基因组组合来确定性状变异的遗传基础。
Understanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through variable pangenomic genes: genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation. However, variable pangenomic genes can be missed in standard genotyping workflows, owing to reliance on aligning short-read sequencing to reference genomes. A popular method for studying the genetic basis of trait variation is linkage mapping, which identifies quantitative trait loci (QTLs), regions of the genome that harbor causative genetic variants. Large-scale linkage mapping in the budding yeast Saccharomyces cerevisiae has found thousands of QTLs affecting myriad yeast phenotypes. To enable the resolution of QTLs caused by variable pangenomic genes, we used long-read sequencing to generate highly complete de novo genome assemblies of 16 diverse yeast isolates. With these assemblies, we resolved QTLs for growth on maltose, sucrose, raffinose, and oxidative stress to specific genes that are absent from the reference genome but present in the broader yeast population at appreciable frequency. Copies of genes also duplicate onto chromosomes where they are absent in the reference genome, and we found that these copies generate additional QTLs whose resolution requires pangenome characterization. Our findings show the need for highly complete genome assemblies to identify the genetic basis of trait variation.
登录
查看更多内容
影响因子：
4.9
作者：
Bozdag GO;Greig D
通讯作者：
Greig D
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
64.8
作者：
D'Angiolo, Melania;De Chiara, Matteo;Liti, Gianni
通讯作者：
Liti, Gianni
影响因子：
4.5
作者：
通讯作者：
--