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Their loss is our gain: regressive evolution in vertebrates provides genomic models for uncovering human disease loci
  1. Christopher A Emerling1,2,
  2. Andrew D Widjaja3,4,
  3. Nancy N Nguyen7,8,
  4. Mark S Springer2
  1. 1Museum of Vertebrate Zoology, University of California, Berkeley, California, USA
  2. 2Department of Biology, University of California, Riverside, California, USA
  3. 3Department of Biochemistry, University of California, Riverside, California, USA
  4. 4Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA
  5. 7Department of Bioengineering, University of California, Riverside, California, USA
  6. 8Department of Bioengineering, University of California, Los Angeles, California, USA
  1. Correspondence to Dr Christopher A Emerling, Museum of Vertebrate Zoology, University of California, Berkeley, CA 94720, USA; caemerling{at}


Throughout Earth’s history, evolution’s numerous natural ‘experiments’ have resulted in a diverse range of phenotypes. Though de novo phenotypes receive widespread attention, degeneration of traits inherited from an ancestor is a very common, yet frequently neglected, evolutionary path. The latter phenomenon, known as regressive evolution, often results in vertebrates with phenotypes that mimic inherited disease states in humans. Regressive evolution of anatomical and/or physiological traits is typically accompanied by inactivating mutations underlying these traits, which frequently occur at loci identical to those implicated in human diseases. Here we discuss the potential utility of examining the genomes of vertebrates that have experienced regressive evolution to inform human medical genetics. This approach is low cost and high throughput, giving it the potential to rapidly improve knowledge of disease genetics. We discuss two well-described examples, rod monochromacy (congenital achromatopsia) and amelogenesis imperfecta, to demonstrate the utility of this approach, and then suggest methods to equip non-experts with the ability to corroborate candidate genes and uncover new disease loci.

  • phylomedicine
  • pseudogenes
  • rod monochromacy
  • amelogenesis imperfecta
  • regressive evolution

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  • Contributors CAE and MSS conceived of the study; CAE, ADW and NNN collected and analysed the data; CAE and MSS wrote the manuscript, ADW and NNN provided comments on the manuscript. All authors approved of the final manuscript.

  • Funding This research was supported by a Lance and Maureen Loomer Endowed Award in Biology (CAE), an NSF Postdoctoral Research Fellowship in Biology (Award 1523943; CAE) and NSF grant DEB-1457735 (MSS).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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