Gains, losses and changes of function after gene duplication: study of the metallothionein family.

Metallothioneins (MT) are small proteins involved in heavy metal detoxification and protection against oxidative stress and cancer. The mammalian MT family originated through a series of duplication events which generated four major genes (MT1 to MT4). MT1 and MT2 encode for ubiquitous proteins, whi...

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Autores principales:	Ana Moleirinho, João Carneiro, Rune Matthiesen, Raquel M Silva, António Amorim, Luísa Azevedo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9472db12e1e4d6e860b83f96873e728
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spelling	oai:doaj.org-article:d9472db12e1e4d6e860b83f96873e7282021-11-18T06:55:17ZGains, losses and changes of function after gene duplication: study of the metallothionein family.1932-620310.1371/journal.pone.0018487https://doaj.org/article/d9472db12e1e4d6e860b83f96873e7282011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21541013/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Metallothioneins (MT) are small proteins involved in heavy metal detoxification and protection against oxidative stress and cancer. The mammalian MT family originated through a series of duplication events which generated four major genes (MT1 to MT4). MT1 and MT2 encode for ubiquitous proteins, while MT3 and MT4 evolved to accomplish specific roles in brain and epithelium, respectively. Herein, phylogenetic, transcriptional and polymorphic analyses are carried out to expose gains, losses and diversification of functions that characterize the evolutionary history of the MT family. The phylogenetic analyses show that all four major genes originated through a single duplication event prior to the radiation of mammals. Further expansion of the MT1 gene has occurred in the primate lineage reaching in humans a total of 13 paralogs, five of which are pseudogenes. In humans, the reading frame of all five MT1 pseudogenes is reconstructed by sequence homology with a functional duplicate revealing that loss of invariant cysteines is the most frequent event accounting for pseudogeneisation. Expression analyses based on EST counts and RT-PCR experiments show that, as for MT1 and MT2, human MT3 is also ubiquitously expressed while MT4 transcripts are present in brain, testes, esophagus and mainly in thymus. Polymorphic variation reveals two deleterious mutations (Cys30Tyr and Arg31Trp) in MT4 with frequencies reaching about 30% in African and Asian populations suggesting the gene is inactive in some individuals and physiological compensation for its loss must arise from a functional equivalent. Altogether our findings provide novel data on the evolution and diversification of MT gene duplicates, a valuable resource for understanding the vast set of biological processes in which these proteins are involved.Ana MoleirinhoJoão CarneiroRune MatthiesenRaquel M SilvaAntónio AmorimLuísa AzevedoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18487 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Moleirinho João Carneiro Rune Matthiesen Raquel M Silva António Amorim Luísa Azevedo Gains, losses and changes of function after gene duplication: study of the metallothionein family.
description	Metallothioneins (MT) are small proteins involved in heavy metal detoxification and protection against oxidative stress and cancer. The mammalian MT family originated through a series of duplication events which generated four major genes (MT1 to MT4). MT1 and MT2 encode for ubiquitous proteins, while MT3 and MT4 evolved to accomplish specific roles in brain and epithelium, respectively. Herein, phylogenetic, transcriptional and polymorphic analyses are carried out to expose gains, losses and diversification of functions that characterize the evolutionary history of the MT family. The phylogenetic analyses show that all four major genes originated through a single duplication event prior to the radiation of mammals. Further expansion of the MT1 gene has occurred in the primate lineage reaching in humans a total of 13 paralogs, five of which are pseudogenes. In humans, the reading frame of all five MT1 pseudogenes is reconstructed by sequence homology with a functional duplicate revealing that loss of invariant cysteines is the most frequent event accounting for pseudogeneisation. Expression analyses based on EST counts and RT-PCR experiments show that, as for MT1 and MT2, human MT3 is also ubiquitously expressed while MT4 transcripts are present in brain, testes, esophagus and mainly in thymus. Polymorphic variation reveals two deleterious mutations (Cys30Tyr and Arg31Trp) in MT4 with frequencies reaching about 30% in African and Asian populations suggesting the gene is inactive in some individuals and physiological compensation for its loss must arise from a functional equivalent. Altogether our findings provide novel data on the evolution and diversification of MT gene duplicates, a valuable resource for understanding the vast set of biological processes in which these proteins are involved.
format	article
author	Ana Moleirinho João Carneiro Rune Matthiesen Raquel M Silva António Amorim Luísa Azevedo
author_facet	Ana Moleirinho João Carneiro Rune Matthiesen Raquel M Silva António Amorim Luísa Azevedo
author_sort	Ana Moleirinho
title	Gains, losses and changes of function after gene duplication: study of the metallothionein family.
title_short	Gains, losses and changes of function after gene duplication: study of the metallothionein family.
title_full	Gains, losses and changes of function after gene duplication: study of the metallothionein family.
title_fullStr	Gains, losses and changes of function after gene duplication: study of the metallothionein family.
title_full_unstemmed	Gains, losses and changes of function after gene duplication: study of the metallothionein family.
title_sort	gains, losses and changes of function after gene duplication: study of the metallothionein family.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d9472db12e1e4d6e860b83f96873e728
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Gains, losses and changes of function after gene duplication: study of the metallothionein family.

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