Barker Juliet, Murray Andrew, Bell Stephen P
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
G3 (Bethesda). 2025 Feb 5;15(2). doi: 10.1093/g3journal/jkae286.
Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms and can serve adaptive functions to specialized somatic cells in multicellular organisms. However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation. To understand the physiological challenges that suddenly increased chromosome content imposes on cells, we used S. cerevisiae to ask how much chromosomal DNA cells may contain and what determines this limit. We generated polyploid cells using 2 distinct methods causing cells to undergo endoreplication and identified the maximum ploidy of these cells, 32-64C. We found that physical determinants that alleviate or exacerbate cell surface stress increase and decrease the limit to ploidy, respectively. We also used these cells to investigate gene expression changes associated with increased ploidy and identified the repression of genes involved in ergosterol biosynthesis. We propose that ploidy is inherently limited by the impacts of growth in size, which accompany whole-genome duplication, to cell surface integrity.
有证据表明，多倍体增加在生物体的进化史上频繁发生，并且对多细胞生物体中的特化体细胞具有适应性功能。然而，所有染色体含量的突然倍增可能给发生这种情况的细胞带来生理挑战。实验研究已将多倍体增加与细胞存活和增殖减少联系起来。为了理解染色体含量突然增加给细胞带来的生理挑战，我们利用酿酒酵母来探究细胞可能容纳多少染色体DNA以及是什么决定了这个限度。我们使用两种不同方法生成多倍体细胞，使细胞进行核内复制，并确定了这些细胞的最大多倍体，即32 - 64C。我们发现，减轻或加剧细胞表面应激的物理决定因素分别增加和降低了多倍体限度。我们还利用这些细胞研究与多倍体增加相关的基因表达变化，并确定了参与麦角固醇生物合成的基因受到抑制。我们提出，多倍体本质上受到伴随全基因组复制的细胞大小增长对细胞表面完整性影响的限制。
