Taylor A, Prasad A, Mueller R Lockridge
Department of Biology, Colorado State University, Fort Collins, CO 80523, USA.
Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
Integr Org Biol. 2024 Jun 19;6(1):obae021. doi: 10.1093/iob/obae021. eCollection 2024.
Evolutionary increases in genome size, cell volume, and nuclear volume have been observed across the tree of life, with positive correlations documented between all three traits. Developmental tempo slows as genomes, nuclei, and cells increase in size, yet the driving mechanisms are poorly understood. To bridge this gap, we use a mathematical model of the somitogenesis clock to link slowed developmental tempo with changes in intra-cellular gene expression kinetics induced by increasing genome size and nuclear volume. We adapt a well-known somitogenesis clock model to two model amphibian species that vary 10-fold in genome size: (3.1 Gb) and (32 Gb). Based on simulations and backed by analytical derivations, we identify parameter changes originating from increased genome and nuclear size that slow gene expression kinetics. We simulate biological scenarios for which these parameter changes mathematically recapitulate slowed gene expression in relative to , and we consider scenarios for which additional alterations in gene product stability and chromatin packing are necessary. Results suggest that slowed degradation rates as well as changes induced by increasing nuclear volume and intron length, which remain relatively unexplored, are significant drivers of slowed developmental tempo.
在整个生命之树中，人们观察到基因组大小、细胞体积和细胞核体积在进化过程中不断增加，并且这三个特征之间存在正相关关系。随着基因组、细胞核和细胞体积的增大，发育节奏会放缓，但其驱动机制仍知之甚少。为了填补这一空白，我们使用体节发生时钟的数学模型，将发育节奏的放缓与基因组大小和细胞核体积增加所诱导的细胞内基因表达动力学变化联系起来。我们将一个著名的体节发生时钟模型应用于两种基因组大小相差10倍的两栖动物模型物种：（3.1Gb）和（32Gb）。基于模拟并得到分析推导的支持，我们确定了源于基因组和细胞核大小增加的参数变化，这些变化会减缓基因表达动力学。我们模拟了一些生物学场景，在这些场景中，这些参数变化在数学上概括了相对于而言基因表达的减缓，并且我们考虑了基因产物稳定性和染色质包装需要额外改变的场景。结果表明，降解速率的减缓以及由细胞核体积和内含子长度增加所引起的变化（这些方面仍相对未被探索）是发育节奏放缓的重要驱动因素。
