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基于主体的核染色体集合建模确定了减数分裂过程中同源配对的决定因素。

Agent-based modeling of nuclear chromosome ensemble identifies determinants of homolog pairing during meiosis.

作者信息

Chriss Ariana, Börner G Valentin, Ryan Shawn D

机构信息

Department of Mathematics and Statistics, Cleveland State University, Cleveland, OH 44115.

Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115.

出版信息

bioRxiv. 2024 Jan 13:2023.08.09.552574. doi: 10.1101/2023.08.09.552574.

Abstract

During meiosis, pairing of homologous chromosomes (homologs) ensures the formation of haploid gametes from diploid precursor cells, a prerequisite for sexual reproduction. Pairing during meiotic prophase I facilitates crossover recombination and homolog segregation during the ensuing reductional cell division. Mechanisms that ensure stable homolog alignment in the presence of an excess of non-homologous chromosomes have remained elusive, but rapid chromosome movements during prophase I appear to play a role in the process. Apart from homolog attraction, provided by early intermediates of homologous recombination, dissociation of non-homologous associations also appears to contribute to homolog pairing, as suggested by the detection of stable non-homologous chromosome associations in pairing-defective mutants. Here, we have developed an agent-based model for homolog pairing derived from the dynamics of a naturally occurring chromosome ensemble. The model simulates unidirectional chromosome movements, as well as collision dynamics determined by attractive and repulsive forces arising from close-range physical interactions. In addition to homolog attraction, chromosome number and size as well as movement velocity and repulsive forces are identified as key factors in the kinetics and efficiency of homologous pairing. Dissociation of interactions between non-homologous chromosomes may contribute to pairing by crowding homologs into a limited nuclear area thus creating preconditions for close-range homolog attraction. Predictions from the model are readily compared to experimental data from budding yeast, parameters can be adjusted to other cellular systems and predictions from the model can be tested via experimental manipulation of the relevant chromosomal features.

摘要

在减数分裂过程中,同源染色体(同源物)的配对确保了从二倍体前体细胞形成单倍体配子,这是有性生殖的一个先决条件。减数第一次分裂前期的配对促进了随后减数分裂细胞分裂过程中的交叉重组和同源物分离。在存在过量非同源染色体的情况下确保同源物稳定排列的机制仍然难以捉摸,但前期I期间的快速染色体运动似乎在这一过程中发挥作用。除了由同源重组的早期中间体提供的同源物吸引外,非同源关联的解离似乎也有助于同源物配对,这一点从配对缺陷突变体中稳定的非同源染色体关联的检测中可以看出。在这里,我们基于自然发生的染色体集合的动力学开发了一种基于主体的同源物配对模型。该模型模拟了单向染色体运动,以及由近距离物理相互作用产生的吸引力和排斥力决定的碰撞动力学。除了同源物吸引外,染色体数量和大小以及运动速度和排斥力被确定为同源配对动力学和效率的关键因素。非同源染色体之间相互作用的解离可能通过将同源物挤入有限的核区域来促进配对,从而为近距离同源物吸引创造前提条件。该模型的预测很容易与芽殖酵母的实验数据进行比较,参数可以调整到其他细胞系统,并且该模型的预测可以通过对相关染色体特征的实验操作来进行测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9837/10802385/f8612f24a30d/nihpp-2023.08.09.552574v2-f0001.jpg

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