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基于图谱的泛基因组揭示了……驯化过程中有害突变的模式。

Graph-Based Pan-Genome Reveals the Pattern of Deleterious Mutations during the Domestication of .

作者信息

Chen Guotao, Shi Guohui, Dai Yi, Zhao Ruilin, Wu Qi

机构信息

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

University of the Chinese Academy of Sciences, Beijing 100049, China.

出版信息

J Fungi (Basel). 2024 Aug 14;10(8):575. doi: 10.3390/jof10080575.

DOI:10.3390/jof10080575
PMID:39194902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11355510/
Abstract

The "cost of domestication" hypothesis suggests that the domestication of wild species increases the number, frequency, and/or proportion of deleterious genetic variants, potentially reducing their fitness in the wild. While extensively studied in domesticated species, this phenomenon remains understudied in fungi. Here, we used , the world's oldest domesticated fungus, as a model to investigate the genomic characteristics of deleterious variants arising from fungal domestication. Employing a graph-based pan-genome approach, we identified 1,297,761 single nucleotide polymorphisms (SNPs), 278,147 insertion/deletion events (indels; <30 bp), and 19,967 non-redundant structural variants (SVs; ≥30 bp) across 687 S. cerevisiae isolates. Comparing these variants with synonymous SNPs (sSNPs) as neutral controls, we found that the majority of the derived nonsynonymous SNPs (nSNPs), indels, and SVs were deleterious. Heterozygosity was positively correlated with the impact of deleterious SNPs, suggesting a role of genetic diversity in mitigating their effects. The domesticated isolates exhibited a higher additive burden of deleterious SNPs (dSNPs) than the wild isolates, but a lower burden of indels and SVs. Moreover, the domesticated showed reduced rates of adaptive evolution relative to the wild . In summary, deleterious variants tend to be heterozygous, which may mitigate their harmful effects, but they also constrain breeding potential. Addressing deleterious alleles and minimizing the genetic load are crucial considerations for future breeding efforts.

摘要

“驯化成本”假说表明,野生物种的驯化会增加有害遗传变异的数量、频率和/或比例,可能降低它们在野外的适应性。虽然在驯化物种中对此进行了广泛研究,但在真菌中这一现象仍研究不足。在这里,我们使用世界上最古老的驯化真菌酿酒酵母作为模型,来研究真菌驯化产生的有害变异的基因组特征。采用基于图谱的泛基因组方法,我们在687株酿酒酵母分离株中鉴定出1,297,761个单核苷酸多态性(SNP)、278,147个插入/缺失事件(indel;<30 bp)和19,967个非冗余结构变异(SV;≥30 bp)。将这些变异与作为中性对照的同义SNP(sSNP)进行比较,我们发现大多数衍生的非同义SNP(nSNP)、indel和SV是有害的。杂合性与有害SNP的影响呈正相关,表明遗传多样性在减轻其影响方面发挥了作用。驯化分离株比野生分离株表现出更高的有害SNP(dSNP)加性负担,但indel和SV的负担较低。此外,驯化菌株相对于野生菌株显示出适应性进化速率降低。总之,有害变异往往是杂合的,这可能减轻它们的有害影响,但也会限制育种潜力。解决有害等位基因并最小化遗传负荷是未来酿酒酵母育种工作的关键考虑因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/932469837d7c/jof-10-00575-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/7b9cb89ddc35/jof-10-00575-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/932469837d7c/jof-10-00575-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/7b9cb89ddc35/jof-10-00575-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/33e88ad06d0e/jof-10-00575-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/3a17762c3113/jof-10-00575-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2db/11355510/63c5aceeef05/jof-10-00575-g004.jpg
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本文引用的文献

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Telomere-to-telomere assemblies of 142 strains characterize the genome structural landscape in Saccharomyces cerevisiae.142 株酿酒酵母的端粒到端粒组装描绘了基因组结构景观。
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Graph construction method impacts variation representation and analyses in a bovine super-pangenome.
图构建方法影响牛超级泛基因组中的变异表示和分析。
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Pangenome graph construction from genome alignments with Minigraph-Cactus.基于 Minigraph-Cactus 的基因组比对构建泛基因组图谱。
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