Insights into the evolution of mammalian telomerase: Platypus TERT shares similarities with genes of birds and other reptiles and localizes on sex chromosomes

Radmila Hrdličková,Henry R Bose,Jiří Nehyba,Frank Grützner,Shu Ly Lim

doi:10.1186/1471-2164-13-216

Radmila Hrdličková, Henry R Bose + Show 3 more

Open Access

https://doi.org/10.1186/1471-2164-13-216

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Abstract

BackgroundThe TERT gene encodes the catalytic subunit of the telomerase complex and is responsible for maintaining telomere length. Vertebrate telomerase has been studied in eutherian mammals, fish, and the chicken, but less attention has been paid to other vertebrates. The platypus occupies an important evolutionary position, providing unique insight into the evolution of mammalian genes. We report the cloning of a platypus TERT (OanTERT) ortholog, and provide a comparison with genes of other vertebrates.ResultsThe OanTERT encodes a protein with a high sequence similarity to marsupial TERT and avian TERT. Like the TERT of sauropsids and marsupials, as well as that of sharks and echinoderms, OanTERT contains extended variable linkers in the N-terminal region suggesting that they were present already in basal vertebrates and lost independently in ray-finned fish and eutherian mammals. Several alternatively spliced OanTERT variants structurally similar to avian TERT variants were identified. Telomerase activity is expressed in all platypus tissues like that of cold-blooded animals and murine rodents. OanTERT was localized on pseudoautosomal regions of sex chromosomes X3/Y2, expanding the homology between human chromosome 5 and platypus sex chromosomes. Synteny analysis suggests that TERT co-localized with sex-linked genes in the last common mammalian ancestor. Interestingly, female platypuses express higher levels of telomerase in heart and liver tissues than do males.ConclusionsOanTERT shares many features with TERT of the reptilian outgroup, suggesting that OanTERT represents the ancestral mammalian TERT. Features specific to TERT of eutherian mammals have, therefore, evolved more recently after the divergence of monotremes.

Highlights

The TERT gene encodes the catalytic subunit of the telomerase complex and is responsible for maintaining telomere length
The platypus occupies an important position in the evolution of the synapsid branch of amniotes providing unique insight into the evolution of mammalian genes
In this work we report the cloning of a platypus TERT ortholog, and provide an evolutionary comparison with TERT proteins of other vertebrates

Summary

Introduction

The TERT gene encodes the catalytic subunit of the telomerase complex and is responsible for maintaining telomere length. We report the cloning of a platypus TERT (OanTERT) ortholog, and provide a comparison with genes of other vertebrates. As a result of the inability of DNA polymerases to replicate chromosomal ends, telomeres shorten with each subsequent cell division. Telomerase plays a critical role in aging and cancer in vertebrates [8,9]. Most human cancer cells express elevated levels of telomerase which is critical for tumor development [11]. The expression and activity of telomerase is tightly regulated principally at the level of TERT transcription (for review see [12]). With the exception of the human AS TERT variant α, which is proposed to be a dominant-negative inhibitor of telomerase activity, the function of the TERT AS variants remains to be determined [18,19]

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