Abstract
Urbanization in low-income countries represents an important inflection point in the epidemiology of disease, with rural populations experiencing high rates of chronic and recurrent infections and urban populations displaying a profile of noncommunicable diseases. To investigate if urbanization alters the expression of genes encoding mitochondrial proteins, we queried gene microarray data from rural and urban populations living in Morocco (GSE17065). The R Bioconductor packages edgeR and limma were used to identify genes with different expression. The experimental design was modeled upon location and sex. Nuclear genes encoding mitochondrial proteins were identified from the MitoCarta2.0 database. Of the 1158 genes listed in the MitoCarta2.0 database, 847 genes (73%) were available for analysis in the Moroccan dataset. The urban-rural comparison with the greatest environmental differences showed that 76.5% of the MitoCarta2.0 genes were differentially expressed, with 97% of the genes having an increased expression in the urban area. Enrichment analysis revealed 367 significantly enriched pathways (adjusted p value < 0.05), with oxidative phosphorylation, insulin secretion and glucose regulations (adj.p values = 6.93E-16) being the top three. Four significantly perturbed KEGG disease pathways were associated with urbanization—three degenerative neurological diseases (Huntington’s, Alzheimer’s, and Parkinson’s diseases) and herpes simplex infection (false discover rate corrected p value (PGFdr) < 0.2). Mitochondrial RNA metabolic processing and translational elongation were the biological processes that had the greatest enrichment (enrichment ratios 14.0 and 14.8, respectively, FDR < 0.5). Our study links urbanization in Morocco with changes in the expression of the nuclear genes encoding mitochondrial proteins.
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This study was supported by the Fogarty International Center, National Institutes of Health (NIH), grant number R25TW011216 and the University of California San Diego (UCSD), Clinical and Translational Research Institute (CTRI) grant number UL1TR001442. The authors thank Barbara Rho for her excellent editing of the manuscript.
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Table S1
Differentially expressed MitoCarta2.0 genes in the Agadir-Boutrouch (urban-rural) geographic comparison. (CSV 119 kb).
Table S2
Gene Set Enrichment Analysis (GSEA) of differentially expressed MitoCarta2.0 genes in the Agadir-Boutrouch (urban-rural) geographic comparison. (CSV 37 kb).
Table S3
Signaling Pathway Impact Analysis (SPIA) of differentially expressed MitoCarta2.0 genes in the Agadir-Boutrouch (urban-rural) geographic comparison. (CSV 12 kb).
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Bickler, S.W., Prieto, J.M., Cauvi, D.M. et al. Differential expression of nuclear genes encoding mitochondrial proteins from urban and rural populations in Morocco. Cell Stress and Chaperones 25, 847–856 (2020). https://doi.org/10.1007/s12192-020-01108-x
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DOI: https://doi.org/10.1007/s12192-020-01108-x