Resumen: A human mitochondrial DNA (mtDNA) transition, m.1555A>G, in the 12S rRNA gene causes non-syndromic hearing loss. However, this pathological mutation is the wild-type allele in orangutan mtDNA. Here we rule out different genetic factors as the reason for its fixation in orangutans and show that aminoglycosides negatively affect the oxidative phosphorylation function by decreasing the synthesis of mtDNA-encoded proteins and the amount and activity of respiratory complex IV. These drugs also diminish the growth rate of orangutan cells. The m.1555G nucleotide is also the wild-type allele in other mammal species and they might be at risk of suffering a mitochondrial disorder if treated with aminoglycosides. Therefore, pharmacogenomic approaches should be used to confirm this possibility. These observations are important for human health. Due to the fact that old age and high frequency are criteria widely used in mitochondrial medicine to rule out a genetic change as being a pathological mutation, our results prevent against simplistic genetic approaches that do not consider the potential effect of environmental conditions. Hence, these results suggest that some ancient and highly frequent human population polymorphisms, such as those defining mtDNA haplogroups, in mitochondrial rRNA genes can be deleterious in association with new environmental conditions. Therefore, as the discovery of ribosomal antibiotics has allowed to fight infectious diseases and this breakthrough can be considered an important scientific advance or ‘progress’, our results suggest that ‘progress’ can also have a negative counterpart and render detrimental many of these mtDNA genotypes. Idioma: Inglés DOI: 10.1093/hmg/ddr350 Año: 2011 Publicado en: HUMAN MOLECULAR GENETICS 20, 21 (2011) ISSN: 0964-6906 Factor impacto JCR: 7.636 (2011) Categ. JCR: GENETICS & HEREDITY rank: 13 / 156 = 0.083 (2011) - Q1 - T1 Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 31 / 287 = 0.108 (2011) - Q1 - T1 Tipo y forma: Article (Published version) Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.) Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)