Author, as appears in the article.: Farre, X; Molina, R; Barteri, F; Timmers, PRHJ; Joshi, PK; Oliva, B; Acosta, S; Esteve-Altava, B; Navarro, A; Muntane, G
Department: Medicina i Cirurgia
URV's Author/s: Muntané Medina, Gerard
Keywords: Aging Brain size Comparative genomics Convergent evolution Evolution Genetics Gwas Heritability Human longevity Maximum lifespan Model Molecular signatures Protein R package Reveals insights Wide association
Abstract: The enormous mammal's lifespan variation is the result of each species' adaptations to their own biological trade-offs and ecological conditions. Comparative genomics have demonstrated that genomic factors underlying both, species lifespans and longevity of individuals, are in part shared across the tree of life. Here, we compared protein-coding regions across the mammalian phylogeny to detect individual amino acid (AA) changes shared by the most long-lived mammals and genes whose rates of protein evolution correlate with longevity. We discovered a total of 2,737 AA in 2,004 genes that distinguish long- and short-lived mammals, significantly more than expected by chance (P = 0.003). These genes belong to pathways involved in regulating lifespan, such as inflammatory response and hemostasis. Among them, a total 1,157 AA showed a significant association with maximum lifespan in a phylogenetic test. Interestingly, most of the detected AA positions do not vary in extant human populations (81.2%) or have allele frequencies below 1% (99.78%). Consequently, almost none of these putatively important variants could have been detected by genome-wide association studies. Additionally, we identified four more genes whose rate of protein evolution correlated with longevity in mammals. Crucially, SNPs located in the detected genes explain a larger fraction of human lifespan heritability than expected, successfully demonstrating for the first time that comparative genomics can be used to enhance interpretation of human genome-wide association studies. Finally, we show that the human longevity-associated proteins are significantly more stable than the orthologous proteins from short-lived mammals, strongly suggesting that general protein stability is linked to increased lifespan.
Thematic Areas: Biochemistry & molecular biology Biodiversidade Biology, miscellaneous Biotecnología Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Ecology, evolution, behavior and systematics Evolutionary biology General medicine Genetics Genetics & heredity Interdisciplinar Medicina i Medicina ii Molecular biology Química
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: gerard.muntane@urv.cat
Record's date: 2024-01-13
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://academic.oup.com/mbe/article/38/11/4948/6326808?login=false
Papper original source: Molecular Biology And Evolution. 38 (11): 4948-4961
APA: Farre, X; Molina, R; Barteri, F; Timmers, PRHJ; Joshi, PK; Oliva, B; Acosta, S; Esteve-Altava, B; Navarro, A; Muntane, G (2021). Comparative Analysis of Mammal Genomes Unveils Key Genomic Variability for Human Life Span. Molecular Biology And Evolution, 38(11), 4948-4961. DOI: 10.1093/molbev/msab219
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1093/molbev/msab219
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV