Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance
A partir d'échantillons sanguins prélevés sur des éléphants, puis à l'aide de base de données génomiques portant sur un ensemble d'espèces animales, cette étude identifie des régions génomiques caractéristiques d'une évolution accélérée, suggère leur implication dans des mécanismes conférant un faible risque de cancer, puis évalue l'association entre les séquences homologues dans l'ADN humain et des phénotypes spécifiques
The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ?33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.
Cell Reports , article en libre accès, 2017