Mammalian Alternative Translation Initiation Is Mostly Nonadaptive.

Molecular Biology and Evolution
Chuan Xu, Jianzhi Zhang

Abstract

Alternative translation initiation (ATLI) refers to the existence of multiple translation initiation sites per gene and is a widespread phenomenon in eukaryotes. ATLI is commonly assumed to be advantageous through creating proteome diversity or regulating protein synthesis. We here propose an alternative hypothesis that ATLI arises primarily from nonadaptive initiation errors presumably due to the limited ability of ribosomes to distinguish sequence motifs truly signaling translation initiation from similar sequences. Our hypothesis, but not the adaptive hypothesis, predicts a series of global patterns of ATLI, all of which are confirmed at the genomic scale by quantitative translation initiation sequencing in multiple human and mouse cell lines and tissues. Similarly, although many codons differing from AUG by one nucleotide can serve as start codons, our analysis suggests that using non-AUG start codons is mostly disadvantageous. These and other findings strongly suggest that ATLI predominantly results from molecular error, requiring a major revision of our understanding of the precision and regulation of translation initiation.

References

Nov 14, 2000·Molecular and Cellular Biology·D R Morris, A P Geballe
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·T V PestovaC U Hellen
Feb 4, 2005·Molecular Biology and Evolution·Michael LynchXin Hong
Mar 22, 2005·Gene·Michele IaconoGraziano Pesole
Jun 17, 2005·Molecular Genetics and Genomics : MGG·Alex V KochetovNikolay A Kolchanov
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Sep 28, 2005·Nucleic Acids Research·Alexander ChurbanovEugene V Koonin
May 12, 2007·Molecular Biology and Evolution·Daniel E Neafsey, James E Galagan
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael Lynch
Jun 7, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alex V Kochetov
Apr 8, 2009·Trends in Genetics : TIG·Christian R LandryStephen W Michnick
Apr 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sarah E CalvoVamsi K Mootha
Nov 26, 2009·Nucleic Acids Research·Yi-Jiun ChenSheng-Chung Lee
Dec 19, 2009·The Journal of Biological Chemistry·Maxim V GerashchenkoVadim N Gladyshev
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Sep 25, 2010·Nucleic Acids Research·Georgii A Bazykin, Alex V Kochetov
Mar 1, 2011·Molecular Biology and Evolution·Chungoo Park, Jianzhi Zhang
Nov 19, 2011·Nature Reviews. Genetics·Tobias Warnecke, Laurence D Hurst
Apr 27, 2012·Comparative and Functional Genomics·Encarnación Martínez-SalasNoemí Fernández
Jun 6, 2012·Nature Structural & Molecular Biology·Colin Echeverría Aitken, Jon R Lorsch
Aug 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sooncheol LeeShu-Bing Qian
Jul 23, 2013·PLoS Computational Biology·Hadas Zur, Tamir Tuller
Oct 29, 2013·Nucleic Acids Research·Klaus WethmarAchim Leutz
Nov 10, 2013·Nucleic Acids Research·Ji Wan, Shu-Bing Qian
Jan 29, 2014·Nature Reviews. Genetics·Nicholas T Ingolia
Feb 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Guixia Xu, Jianzhi Zhang
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Aug 30, 2014·Molecular Systems Biology·William L NodererClifford L Wang
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michael LynchShelley Sazer
Dec 9, 2014·Nature Methods·Xiangwei GaoShu-Bing Qian
Feb 5, 2015·Trends in Genetics : TIG·Eleonora de Klerk, Peter A C 't Hoen
Jun 10, 2015·Nature Reviews. Genetics·Jianzhi Zhang, Jian-Rong Yang
Oct 4, 2015·Nature·Peter H SudmantJan O Korbel

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Citations

Jul 29, 2021·Cell Reports·Chuan Xu, Jianzhi Zhang

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