酵母中携带缺失的线粒体DNA的遗传偏向性:拷贝数和细胞内选择的作用。

Inheritance bias of deletion-harbouring mtDNA in yeast: The role of copy number and intracellular selection.

作者信息

Kashko Nataliia D, Muravyov Georgii, Karavaeva Iuliia, Glagoleva Elena S, Logacheva Maria D, Garushyants Sofya K, Knorre Dmitry A

机构信息

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.

Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.

出版信息

PLoS Genet. 2025 Jun 24;21(6):e1011737. doi: 10.1371/journal.pgen.1011737. eCollection 2025 Jun.

Abstract

During sexual reproduction, fungi usually inherit mtDNA from both parents, however, the distribution of the mtDNA in the progeny can be biased toward some mtDNA variants. For example, crossing Saccharomyces cerevisiae strain carrying wild type (rho+) mtDNA with the strain carrying mutant mtDNA variant with a large deletion (rho-) can produce up to 99-100% of rho- diploid progeny. Two factors could contribute to this phenomenon. First, rho- cells may accumulate more copies of mtDNA molecules per cell than wild-type cells, making rho- mtDNA the prevalent mtDNA molecule in zygotes. This consequently leads to a high portion of rho- diploid cells in the offspring. Second, rho- mtDNA may have a competitive advantage within heteroplasmic cells, and therefore could displace rho+ mtDNA in a series of generations, regardless of their initial ratio. To assess the contribution of these factors, we investigated the genotypes and phenotypes of twenty two rho- yeast strains. We found that indeed rho- cells have a higher mtDNA copy number per cell than rho+ strains. Using an in silico modelling of mtDNA selection and random drift in heteroplasmic yeast cells, we assessed the intracellular fitness of mutant mtDNA variants. Our model indicates that both higher copy numbers and intracellular fitness advantage of the rho- mtDNA contribute to the biased inheritance of rho- mtDNA.

摘要

在有性生殖过程中,真菌通常从双亲那里继承线粒体DNA(mtDNA),然而,mtDNA在子代中的分布可能偏向于某些mtDNA变体。例如,将携带野生型(rho+)mtDNA的酿酒酵母菌株与携带大段缺失的突变型mtDNA变体(rho-)的菌株杂交,可产生高达99 - 100%的rho-二倍体子代。有两个因素可能导致这种现象。首先,rho-细胞可能比野生型细胞每个细胞积累更多拷贝的mtDNA分子,使得rho- mtDNA成为合子中占主导的mtDNA分子。这进而导致后代中rho-二倍体细胞的比例很高。其次,rho- mtDNA在异质细胞内可能具有竞争优势,因此在一系列世代中能够取代rho+ mtDNA,无论其初始比例如何。为了评估这些因素的作用,我们研究了22个rho-酵母菌株的基因型和表型。我们发现rho-细胞确实比rho+菌株每个细胞具有更高的mtDNA拷贝数。通过对异质酵母细胞中mtDNA选择和随机漂移进行计算机模拟,我们评估了突变型mtDNA变体在细胞内的适应性。我们的模型表明,rho- mtDNA的高拷贝数和细胞内适应性优势都导致了rho- mtDNA的偏向性遗传。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/876f/12186888/9484f32c2901/pgen.1011737.g001.jpg

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