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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081807/ https://www.ncbi.nlm.nih.gov/pubmed/21541013 http://dx.doi.org/10.1371/journal.pone.0018487 |
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author | Moleirinho, Ana Carneiro, João Matthiesen, Rune Silva, Raquel M. Amorim, António Azevedo, Luísa |
author_facet | Moleirinho, Ana Carneiro, João Matthiesen, Rune Silva, Raquel M. Amorim, António Azevedo, Luísa |
author_sort | Moleirinho, Ana |
collection | PubMed |
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 | Text |
id | pubmed-3081807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30818072011-05-03 Gains, Losses and Changes of Function after Gene Duplication: Study of the Metallothionein Family Moleirinho, Ana Carneiro, João Matthiesen, Rune Silva, Raquel M. Amorim, António Azevedo, Luísa PLoS One Research Article 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. Public Library of Science 2011-04-25 /pmc/articles/PMC3081807/ /pubmed/21541013 http://dx.doi.org/10.1371/journal.pone.0018487 Text en Moleirinho et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Moleirinho, Ana Carneiro, João Matthiesen, Rune Silva, Raquel M. Amorim, António Azevedo, Luísa Gains, Losses and Changes of Function after Gene Duplication: Study of the Metallothionein Family |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081807/ https://www.ncbi.nlm.nih.gov/pubmed/21541013 http://dx.doi.org/10.1371/journal.pone.0018487 |
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