Ancient and recent adaptive evolution of primate non-homologous end joining genes.

In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of th...

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Autores principales:	Ann Demogines, Alysia M East, Ji-Hoon Lee, Sharon R Grossman, Pardis C Sabeti, Tanya T Paull, Sara L Sawyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8f7c3f34c7be4c1a8a2d235dc7ea4ebf
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spelling	oai:doaj.org-article:8f7c3f34c7be4c1a8a2d235dc7ea4ebf2021-11-18T06:17:57ZAncient and recent adaptive evolution of primate non-homologous end joining genes.1553-73901553-740410.1371/journal.pgen.1001169https://doaj.org/article/8f7c3f34c7be4c1a8a2d235dc7ea4ebf2010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20975951/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes.Ann DemoginesAlysia M EastJi-Hoon LeeSharon R GrossmanPardis C SabetiTanya T PaullSara L SawyerPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 6, Iss 10, p e1001169 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Ann Demogines Alysia M East Ji-Hoon Lee Sharon R Grossman Pardis C Sabeti Tanya T Paull Sara L Sawyer Ancient and recent adaptive evolution of primate non-homologous end joining genes.
description	In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes.
format	article
author	Ann Demogines Alysia M East Ji-Hoon Lee Sharon R Grossman Pardis C Sabeti Tanya T Paull Sara L Sawyer
author_facet	Ann Demogines Alysia M East Ji-Hoon Lee Sharon R Grossman Pardis C Sabeti Tanya T Paull Sara L Sawyer
author_sort	Ann Demogines
title	Ancient and recent adaptive evolution of primate non-homologous end joining genes.
title_short	Ancient and recent adaptive evolution of primate non-homologous end joining genes.
title_full	Ancient and recent adaptive evolution of primate non-homologous end joining genes.
title_fullStr	Ancient and recent adaptive evolution of primate non-homologous end joining genes.
title_full_unstemmed	Ancient and recent adaptive evolution of primate non-homologous end joining genes.
title_sort	ancient and recent adaptive evolution of primate non-homologous end joining genes.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/8f7c3f34c7be4c1a8a2d235dc7ea4ebf
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Ancient and recent adaptive evolution of primate non-homologous end joining genes.

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