Please use this identifier to cite or link to this item: http://hdl.handle.net/10216/109251
Author(s): Pereira, L
Soares, P
Triska, P
Rito, T
Waerden, Avd
Li, B
Radivojac, P
Samuels, DC
Title: Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential
Publisher: Nature Publishing Group
Issue Date: 2014
Abstract: Mitochondrial proteins are coded by nuclear (nDNA) and mitochondrial (mtDNA) genes, implying a complex cross-talk between the two genomes. Here we investigated the diversity displayed in 104 nuclear-coded mitochondrial proteins from 1,092 individuals from the 1000 Genomes dataset, in order to evaluate if these genes are under the effects of purifying selection and how that selection compares with their mitochondrial encoded counterparts. Only the very rare variants (frequency < 0.1%) in these nDNA genes are indistinguishable from a random set from all possible variants in terms of predicted pathogenicity score, but more frequent variants display distinct signs of purifying selection. Comparisons of selection strength indicate stronger selection in the mtDNA genes compared to this set of nDNA genes, accounted for by the high hydrophobicity of the proteins coded by the mtDNA. Most of the predicted pathogenic variants in the nDNA genes were restricted to a single continental population. The proportion of individuals having at least one potential pathogenic mutation in this gene set was significantly lower in Europeans than in Africans and Asians. This difference may reflect demographic asymmetries, since African and Asian populations experienced main expansions in middle Holocene, while in Europeans the main expansions occurred earlier in the post-glacial period.
Subject: African Continental Ancestry Group/genetics
Asian Continental Ancestry Group/genetics
Cell Nucleus/genetics
DNA/genetics
DNA/metabolism
DNA Mitochondrial/genetics
DNA Mitochondrial/metabolism
Databases Genetic
European Continental Ancestry Group/genetics
Genetic Variation
Humans
Hydrophobic and Hydrophilic Interactions
Mitochondrial Proteins/chemistry
Mitochondrial Proteins/immunology
Mitochondrial Proteins/metabolism
Polymorphism Genetic
URI: http://hdl.handle.net/10216/109251
Source: Scientific Reports, vol. 4:7155
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/113832/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: http://creativecommons.org/licenses/by-nc-nd/4.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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