Biological processes modulating longevity across primates : A phylogenetic genome-phenome analysis
Muntané, Gerard (Universitat Pompeu Fabra)
Farré Ramon, Xavier (Universitat Pompeu Fabra)
Rodriguez, Juan Antonio (Centre de Regulació Genòmica)
Pegueroles Queralt, Maria Cinta (Universitat Pompeu Fabra)
Hughes, David A. (University of Bristol)
de Magalhaes, Joao Pedro (University of Liverpool)
Gabaldón, Toni (Centre de Regulació Genòmica)
Navarro, Arcadi 1969- (Universitat Pompeu Fabra)

Fecha:	2018
Resumen:	Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino-acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.
Ayudas:	Agencia Estatal de Investigación BFU2012-38236 Ministerio de Economía y Competitividad BFU2015-68649-P Generalitat de Catalunya 2014/SGR-1311 Generalitat de Catalunya 2014/SGR-866 Generalitat de Catalunya 2014/BP-B00157 Ministerio de Economía y Competitividad PT13/0001/0026 Ministerio de Economía y Competitividad MDM-2014-0370
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Aging ; Evolution ; Genotype-phenotype ; Longevity ; Primates
Publicado en:	Molecular biology and evolution, Vol. 35, Num. 8 (August 2018) , p. 1990-2004, ISSN 1537-1719

DOI: 10.1093/molbev/msy105
PMID: 29788292

15 p, 1.4 MB

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