On the rate of aneuploidy reversion in a wild yeast model.

IF 3.3 3区 生物学 Q2 GENETICS & HEREDITY
Genetics Pub Date : 2024-11-25 DOI:10.1093/genetics/iyae196
James Hose, Qi Zhang, Nathaniel P Sharp, Audrey P Gasch
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Abstract

Aneuploidy, arising from gain or loss of chromosomes due to nondisjunction, is a special class of mutation. It can create significant phenotypic changes by altering abundance of hundreds of genes in a single event, providing material for adaptive evolution. But it can also incur large fitness costs relative to other types of mutations. Understanding mutational dynamics of aneuploidy is important for modeling its impact in nature, but aneuploidy rates are difficult to measure accurately. One challenge is that aneuploid karyotypes may revert back to euploidy, biasing forward mutation rate estimates - yet the rate of aneuploidy reversion is largely uncharacterized. Furthermore, current rate estimates are confounded because fitness differences between euploids and aneuploids are typically not accounted for in rate calculations. We developed a unique fluctuation assay in a wild-yeast model to measure the rate of extra-chromosome loss across three aneuploid chromosomes, while accounting for fitness differences between aneuploid and euploid cells. We show that incorporating fitness effects is essential to obtain accurate estimates of aneuploidy rates. Furthermore, the rate of extra-chromosome loss, separate from karyotype fitness differences, varies across chromosomes. We also measured rates in a strain lacking RNA-binding protein Ssd1, important for aneuploidy tolerance and implicated in chromosome segregation. We found no role for Ssd1 in the loss of native aneuploid chromosomes, although it did impact an engineered chromosome XV with a perturbed centromeric sequence. We discuss the impacts and challenges of modeling aneuploidy dynamics in real world situations.

野生酵母模型中的非整倍体逆转率
非整倍体是一种特殊的突变,它是由于染色体的非连接而导致的染色体增殖或缺失。它可以在一次事件中改变数百个基因的丰度,从而产生重大的表型变化,为适应性进化提供素材。但与其他类型的突变相比,它也会产生巨大的适应成本。了解非整倍体的突变动态对于模拟其在自然界中的影响非常重要,但非整倍体率很难准确测量。其中一个挑战是,非整倍体核型可能会恢复到整倍体,从而使前瞻性突变率估计值出现偏差--然而非整倍体恢复率在很大程度上还没有定性。此外,由于在计算突变率时通常不考虑优倍体和非整倍体之间的适应性差异,因此目前的突变率估算结果受到了干扰。我们在野生酵母模型中开发了一种独特的波动测定法,用于测量三条非整倍体染色体的染色体外丢失率,同时考虑到非整倍体细胞和优倍体细胞之间的体质差异。我们的研究表明,要获得非整倍体率的准确估算值,就必须考虑适合度效应。此外,染色体外损失率与核型适性差异无关,在不同染色体上也有差异。我们还测量了缺乏 RNA 结合蛋白 Ssd1 的菌株的非整倍体率。我们没有发现 Ssd1 在原生非整倍体染色体的丢失中起任何作用,但它确实影响了具有中心粒序列紊乱的工程染色体 XV。我们讨论了在真实世界中建立非整倍体动态模型的影响和挑战。
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来源期刊
Genetics
Genetics GENETICS & HEREDITY-
CiteScore
6.90
自引率
6.10%
发文量
177
审稿时长
1.5 months
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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