Article | Volume 22, ISSUE 10 , P2742-2755, March 06, 2018

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    Highlights

    • Accelerated evolution in terrestrial, aerial, marine, and subterranean mammals
    • Accelerated regions (ARs) uncover diverse putative functional elements
    • Elephant ARs reveal candidate mechanisms to decrease mutations and cancer risk
    • Human AR homologs indicate concordance between clinical and species’ phenotypes
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    Summary

    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.

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    References

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