Lai Alvina G, Pouchkina-Stantcheva Natalia, Di Donfrancesco Alessia, Kildisiute Gerda, Sahu Sounak, Aboobaker A Aziz
Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK.
BMC Evol Biol. 2017 Apr 26;17(1):107. doi: 10.1186/s12862-017-0949-4.
Most animals employ telomerase, which consists of a catalytic subunit known as the telomerase reverse transcriptase (TERT) and an RNA template, to maintain telomere ends. Given the importance of TERT and telomere biology in core metazoan life history traits, like ageing and the control of somatic cell proliferation, we hypothesised that TERT would have patterns of sequence and regulatory evolution reflecting the diverse life histories across the Animal Kingdom.
We performed a complete investigation of the evolutionary history of TERT across animals. We show that although TERT is almost ubiquitous across Metazoa, it has undergone substantial sequence evolution within canonical motifs. Beyond the known canonical motifs, we also identify and compare regions that are highly variable between lineages, but show conservation within phyla. Recent data have highlighted the importance of alternative splice forms of TERT in non-canonical functions and although animals may share some conserved introns, we find that the selection of exons for alternative splicing appears to be highly variable, and regulation by alternative splicing appears to be a very dynamic feature of TERT evolution. We show that even within a closely related group of triclad flatworms, where alternative splicing of TERT was previously correlated with reproductive strategy, we observe highly diverse splicing patterns.
Our work establishes that the evolutionary history and structural evolution of TERT involves previously unappreciated levels of change and the emergence of lineage specific motifs. The sequence conservation we describe within phyla suggests that these new motifs likely serve essential biological functions of TERT, which along with changes in splicing, underpin diverse functions of TERT important for animal life histories.
大多数动物利用端粒酶来维持染色体末端,端粒酶由一个称为端粒酶逆转录酶(TERT)的催化亚基和一个RNA模板组成。鉴于TERT和端粒生物学在核心后生动物生活史特征(如衰老和体细胞增殖控制)中的重要性,我们推测TERT会有反映动物界不同生活史的序列和调控进化模式。
我们对动物界TERT的进化历史进行了全面研究。我们发现,尽管TERT在后生动物中几乎无处不在,但它在经典基序内经历了大量的序列进化。除了已知的经典基序,我们还识别并比较了不同谱系间高度可变但在门内保守的区域。最近的数据突出了TERT的可变剪接形式在非经典功能中的重要性,尽管动物可能共享一些保守内含子,但我们发现用于可变剪接的外显子选择似乎高度可变,并且可变剪接调控似乎是TERT进化的一个非常动态的特征。我们表明,即使在一组密切相关的三肠扁形虫中,此前TERT的可变剪接与生殖策略相关,我们也观察到了高度多样的剪接模式。
我们的研究确定,TERT的进化历史和结构进化涉及此前未被认识到的变化程度以及谱系特异性基序的出现。我们在门内描述的序列保守性表明,这些新基序可能发挥TERT的重要生物学功能,这些功能连同剪接变化,支撑了TERT对动物生活史重要的多种功能。