Abstract

BackgroundMost 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.ResultsWe 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.ConclusionsOur 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.

Highlights

  • 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

  • While TERT proteins perform core functions across eukaryotes, not much is known about how conserved or not TERT protein structure is between different metazoan lineages

  • In order to address this, we set out to define the structure of TERT in the metazoan ancestor and use this as a basis for comparison amongst animals

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Summary

Introduction

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. Telomeres function as protective nucleoprotein structures that guard chromosome ends against the action of nucleases, DNA damage signalling and nucleolytic degradation [1,2,3]. Cells in culture have a finite replicative lifespan limiting the number of times a cell can divide, and eventually senesce [6]. This has since been shown to be a key mechanism in protecting against cancer and may contribute to causing a decline in physiological functions and organismal ageing [7,8,9,10,11,12]. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

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