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结局好一切都好:为什么大型物种的端粒较短。

All's well that ends well: why large species have short telomeres.

机构信息

Department of Pathology, University of Washington, Seattle, WA 98195, USA

Department of Pathology, University of Washington, Seattle, WA 98195, USA.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2018 Mar 5;373(1741). doi: 10.1098/rstb.2016.0448.

Abstract

Among mammal species, almost all life-history traits are strongly size dependent. This size dependence even occurs at a molecular level. For example, both telomere length and telomerase expression show a size-dependent threshold. With some exceptions, species smaller than approximately 2 kg express telomerase, while species larger than that do not. Among species greater than approximately 5 kg, telomeres tend to be short-less than 25 kb-while among smaller species, some species have short and some have long telomeres. Here, we present a model to explore the role of body size-dependent trade-offs in shaping this threshold. We assume that selection favours short telomeres as a mechanism to protect against cancer. At the same time, selection favours long telomeres as a protective mechanism against DNA damage and replicative senescence. The relative importance of these two selective forces will depend on underlying intrinsic mortality and risk of cancer, both of which are size-dependent. Results from this model suggest that a cost-benefit model for the evolution of telomere length could explain phylogenetic patterns observed within the Class Mammalia. In addition, the model suggests a general conceptual framework to think about the role that body size plays in the evolution of tumour suppressor mechanisms.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

摘要

在哺乳动物物种中,几乎所有的生活史特征都强烈依赖于体型。这种体型依赖性甚至在分子水平上也存在。例如,端粒长度和端粒酶表达都显示出依赖于体型的阈值。除了一些例外,体重小于约 2 公斤的物种表达端粒酶,而大于该体重的物种则不表达。在大于约 5 公斤的物种中,端粒往往较短——小于 25 kb——而在较小的物种中,有些物种的端粒短,有些则长。在这里,我们提出了一个模型来探讨体型依赖性权衡在形成这种阈值中的作用。我们假设,选择有利于短端粒作为一种预防癌症的机制。同时,选择有利于长端粒作为一种防止 DNA 损伤和复制性衰老的保护机制。这两种选择力量的相对重要性将取决于潜在的内在死亡率和癌症风险,这两者都依赖于体型。该模型的结果表明,端粒长度进化的成本效益模型可以解释在哺乳动物类中观察到的系统发育模式。此外,该模型还提出了一个一般的概念框架,用于思考体型在肿瘤抑制机制进化中的作用。本文是主题为“理解端粒动力学多样性”的一部分。

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