Evolution of termination codons of proteins and the TAG-TGA paradox

Author:

Trexler Mária,Bányai László,Kerekes Krisztina,Patthy LászlóORCID

Abstract

AbstractIn most eukaryotes and prokaryotes TGA is used at a significantly higher frequency than TAG as termination codon of protein-coding genes. Although this phenomenon has been recognized several years ago, there is no generally accepted explanation for the TAG-TGA paradox. Our analyses of human mutation data revealed that out of the eighteen sense codons that can give rise to a nonsense codon by single base substitution, the CGA codon is exceptional: it gives rise to the TGA stop codon at an order of magnitude higher rate than the other codons. Here we propose that the TAG-TGA paradox is due to methylation and hypermutabilty of CpG dinucleotides. In harmony with this explanation, we show that the coding genomes of organisms with strong CpG methylation have a significant bias for TGA whereas those from organisms that lack CpG methylation use TGA and TAG termination codons with similar probability.

Funder

Nemzeti Kutatási Fejlesztési és Innovációs Hivatal

ELKH Research Centre for Natural Sciences

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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