Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance

Elliott Ferris, Lisa M. Abegglen, Joshua D. Schiffman, Christopher Gregg

Research output: Contribution to journalArticle

  • 3 Citations

Abstract

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. Ferris et al. report an analysis of accelerated evolution in the elephant, little brown bat, big brown bat, orca, dolphin, naked mole rate, and thirteen-lined ground squirrel that reveals candidate functional genomic elements for shaping somatic mutation rate, cancer risk, digit development, immunity, glaucoma, pigmentation, and other clinical phenotypes.

LanguageEnglish (US)
Pages2601-2614
Number of pages14
JournalCell Reports
Volume22
Issue number10
DOIs
StatePublished - Mar 6 2018

Fingerprint

Genes
Mutation
Dolphins
Phenotype
Sciuridae
Neoplasms
Mammals
Ubiquitin-Protein Ligases
DNA
Mole Rats
Rats
Genome
Repair
Fanconi Anemia
Pigmentation
Mutation Rate
DNA Repair
Glaucoma
DNA Damage
Immunity

Keywords

  • accelerated evolution
  • cancer
  • elephant
  • enhancer
  • epigenetics
  • naked mole rat
  • Peto's paradox
  • phylogenomics
  • regulatory element
  • somatic mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance. / Ferris, Elliott; Abegglen, Lisa M.; Schiffman, Joshua D.; Gregg, Christopher.

In: Cell Reports, Vol. 22, No. 10, 06.03.2018, p. 2601-2614.

Research output: Contribution to journalArticle

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