Progressive pseudogenization: vitamin C synthesis and its loss in bats

Mol Biol Evol. 2011 Feb;28(2):1025-31. doi: 10.1093/molbev/msq286. Epub 2010 Oct 29.


For the past 50 years, it was believed that all bats, like humans and guinea pigs, did not synthesize vitamin C (Vc) because they lacked activity of L-gulonolactone oxidase (GULO) in their livers. Humans and guinea pigs lack the activity due to pseudogenization of GULO in their genomes, but there is no genetic evidence to show whether such loss in bats is caused by pseudogenization. Unexpectedly, our successful molecular cloning in one frugivorous bat (Rousettus leschenaultii) and one insectivorous bat (Hipposideros armiger) ascertains that no pseudogenization occurs in these species. Furthermore, we find normal GULO protein expression using bat-specific anti-GULO polyclonal antibodies in bats, evaluated by Western blotting. Most surprisingly, GULO activity assays reveal that these two bat species have retained the ability to synthesize Vc, but at low levels compared with the mouse. It is known that bats in the genus Pteropus have lost GULO activity. We then found that functional constraints acting on the GULO of Pteropus vampyrus (which lost its function) are relaxed. These results imply that the ability to synthesize Vc in bats has not been lost completely in species as previously thought. We also suggest that the evolution of bat GULO genes can be a good model to study genetic processes associated with loss-of-function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ascorbic Acid / biosynthesis*
  • Chiroptera / genetics*
  • Evolution, Molecular*
  • L-Gulonolactone Oxidase / genetics
  • Liver / metabolism
  • Molecular Sequence Data
  • Pseudogenes*
  • Sequence Alignment


  • L-Gulonolactone Oxidase
  • Ascorbic Acid