Adaptive evolution of tight junction protein claudin-14 in echolocating whales

Gene. 2013 Nov 10;530(2):208-14. doi: 10.1016/j.gene.2013.08.034. Epub 2013 Aug 18.


Toothed whales and bats have independently evolved specialized ultrasonic hearing for echolocation. Recent findings have suggested that several genes including Prestin, Tmc1, Pjvk and KCNQ4 appear to have undergone molecular adaptations associated with the evolution of this ultrasonic hearing in mammals. Here we studied the hearing gene Cldn14, which encodes the claudin-14 protein and is a member of tight junction proteins that functions in the organ of Corti in the inner ear to maintain a cationic gradient between endolymph and perilymph. Particular mutations in human claudin-14 give rise to non-syndromic deafness, suggesting an essential role in hearing. Our results uncovered two bursts of positive selection, one in the ancestral branch of all toothed whales and a second in the branch leading to the delphinid, phocoenid and ziphiid whales. These two branches are the same as those previously reported to show positive selection in the Prestin gene. Furthermore, as with Prestin, the estimated hearing frequencies of whales significantly correlate with numbers of branch-wise non-synonymous substitutions in Cldn14, but not with synonymous changes. However, in contrast to Prestin, we found no evidence of positive selection in bats. Our findings from Cldn14, and comparisons with Prestin, strongly implicate multiple loci in the acquisition of echolocation in cetaceans, but also highlight possible differences in the evolutionary route to echolocation taken by whales and bats.

Keywords: Bat; Cdh23; Cetacean; Cldn14; Hearing; IHC; KCNQ4; Natural selection; OHC; Otof; Pcdh15; Pjvk; Tmc1; cadherin 23 gene; claudin-14 gene; inner hair cell; otoferlin gene; outer hair cell; pejvakin gene; potassium voltage-gated channel subfamily KQT member 4 gene; protocadherin 15 gene; transmembrane cochlear-expressed gene 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological / genetics*
  • Animals
  • Bayes Theorem
  • Chiroptera / classification
  • Chiroptera / genetics*
  • Chiroptera / metabolism
  • Claudins / chemistry
  • Claudins / classification
  • Claudins / genetics*
  • Claudins / metabolism
  • Echolocation / physiology*
  • Evolution, Molecular*
  • Hearing / physiology
  • Humans
  • Organ of Corti / physiology
  • Phylogeny
  • Tight Junctions / physiology
  • Whales / classification
  • Whales / genetics*
  • Whales / metabolism


  • Claudins
  • claudin 14