Article open access publication

Functional roles of Aves class-specific cis-regulatory elements on macroevolution of bird-specific features

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 8, 1, 2017

DOI:10.1038/ncomms14229, Dimensions: pub.1083686069, PMC: PMC5473641, PMID: 28165450,


Seki, Ryohei (1) (2)
Li, Cai (3) (4) (5)
Fang, Qi (4) (5)
Hu, Jiang (4)
Pan, Hailin (4) (5)
Liu, Yang (4)
Zhou, Qi (8)
Xu, Xing (9)
Irie, Naoki * (10)
Tamura, Koji * (2)
Zhang, Guo-Jie * (3) (4) (5)

* Corresponding author



  1. (1) National Institute of Genetics, grid.288127.6
  2. (2) Tohoku University, grid.69566.3a
  3. (3) University of Copenhagen, grid.5254.6, KU
  4. (4) Kunming Institute of Zoology, grid.419010.d
  5. (5) Beijing Genomics Institute, grid.21155.32
  6. (6) University of Minnesota, grid.17635.36
  7. (7) Norwegian University of Science and Technology, grid.5947.f
  8. (8) University of California, Berkeley, grid.47840.3f
  9. (9) Institute of Vertebrate Paleontology and Paleoanthropology, grid.458456.e
  10. (10) University of Tokyo, grid.26999.3d


Unlike microevolutionary processes, little is known about the genetic basis of macroevolutionary processes. One of these magnificent examples is the transition from non-avian dinosaurs to birds that has created numerous evolutionary innovations such as self-powered flight and its associated wings with flight feathers. By analysing 48 bird genomes, we identified millions of avian-specific highly conserved elements (ASHCEs) that predominantly (>99%) reside in non-coding regions. Many ASHCEs show differential histone modifications that may participate in regulation of limb development. Comparative embryonic gene expression analyses across tetrapod species suggest ASHCE-associated genes have unique roles in developing avian limbs. In particular, we demonstrate how the ASHCE driven avian-specific expression of gene Sim1 driven by ASHCE may be associated with the evolution and development of flight feathers. Together, these findings demonstrate regulatory roles of ASHCEs in the creation of avian-specific traits, and further highlight the importance of cis-regulatory rewiring during macroevolutionary changes.


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