Telomeres ensure chromosome length homeostasis and protection from catastrophic end-to-end chromosome fusions. All eukaryotes require this essential, strictly conserved telomere-dependent genome preservation. However, recent evolutionary analyses of mammals, plants, and flies report pervasive rapid evolution of telomere proteins. The causes of this paradoxical observation – that unconserved machinery underlies an essential, conserved function – remain enigmatic. Indeed, these fast-evolving telomere proteins bind, extend, and protect telomeric DNA, which itself evolves slowly in most systems. We hypothesize that the universally fast-evolving subtelomere – the telomere-adjacent, repetitive sequence – is a primary driver of the ‘telomere paradox’. Under this model, radical sequence changes in the subtelomere perturb subtelomere-dependent, telomere functions. Compromised telomere function then spurs adaptation of telomere proteins to maintain telomere length homeostasis and protection. We propose an experimental framework that leverages both protein divergence and subtelomeric sequence divergence to test the hypothesis that subtelomere sequence evolution shapes recurrent innovation of telomere machinery.

端粒可确保染色体长度的稳态，并防止灾难性的端到端染色体融合。所有真核生物都需要这种基本的，严格保守的端粒依赖性基因组保存方法。然而，最近对哺乳动物，植物和果蝇的进化分析报告了端粒蛋白的普遍快速进化。这种自相矛盾的观察的原因-不保守的机械是基本的，保守的功能的基础-仍然是个谜。实际上，这些快速发展的端粒蛋白结合，延伸和保护端粒DNA，端粒DNA本身在大多数系统中进化缓慢。我们假设普遍快速发展的亚端粒-端粒相邻的重复序列-是“端粒悖论”的主要驱动力。在此模型下，自由基序列会在依赖于亚端粒的亚端粒扰动下发生变化，端粒功能。然后，端粒功能受损会刺激端粒蛋白的适应性，以维持端粒长度的稳态和保护作用。我们提出了一个实验框架，该框架利用蛋白质差异和亚端粒序列差异来测试以下假设：亚端粒序列进化塑造了端粒机制的反复创新。