Recent Loss of Vitamin C Biosynthesis Ability in Bats

Abstract

The traditional assumption that bats cannot synthesize vitamin C (Vc) has been challenged recently. We have previously shown that two Old World bat species (Rousettus leschenaultii and Hipposideros armiger) have functional L-gulonolactone oxidase (GULO), an enzyme that catalyzes the last step of Vc biosynthesis de novo. Given the uncertainties surrounding when and how bats lost GULO function, exploration of gene evolutionary patterns is needed. We therefore sequenced GULO genes from 16 bat species in 5 families, aiming to establish their evolutionary histories. In five cases we identified pseudogenes for the first time, including two cases in the genus Pteropus (P. pumilus and P. conspicillatus) and three in family Hipposideridae (Coelops frithi, Hipposideros speoris, and H. bicolor). Evolutionary analysis shows that the Pteropus clade has the highest ω ratio and has been subjected to relaxed selection for less than 3 million years. Purifying selection acting on the pseudogenized GULO genes of roundleaf bats (family Hipposideridae) suggests they have lost the ability to synthesize Vc recently. Limited mutations in the reconstructed GULO sequence of the ancestor of all bats contrasts with the many mutations in the ancestral sequence of recently emerged Pteropus bats. We identified at least five mutational steps that were then related to clade origination times. Together, our results suggest that bats lost the ability to biosynthesize vitamin C recently by exhibiting stepwise mutation patterns during GULO evolution that can ultimately lead to pseudogenization.

Comparative genomics reveals insights into avian genome evolution and adaptation

“…In contrast, intact GULO was recovered from the third oscine species, American crow, and the basal passerine rifleman ( Acanthisitta chloris ) (table S43). Similar to mammals (74), this pseudogenization was caused by the loss of different exons and lethal mutations. We also found purifying selection has dominated GULO evolution, from the ancestral amniote node (d N /d S = 0.096) to ancestral birds (d N /d S = 0.133) and mammals (d N /d S = 0.355), suggesting conservation of the ability to synthesize Vc both before and after avian divergence.…”

Controlling for Phylogenetic Relatedness and Evolutionary Rates Improves the Discovery of Associations Between Species’ Phenotypic and Genomic Differences

“…Among the four nonvitamin C synthesizing lineages, the megabat ( P. vampyrus ) has lost this trait most recently, as closely related bats are able to synthesize vitamin C and the Gulo gene is intact in other species of the Pteropus genus ( Cui et al 2011a , b ). Since our simulations showed that there is lower sensitivity to detect genotype–phenotype associations for recent trait losses, we tested if excluding P. vampyrus from the list of trait-loss lineages would increase the sensitivity to detect Gulo exons.…”

A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

“…A targeted Gulo knockout in mouse abolishes the ability to synthesize vitamin C (Maeda et al, 2000). Inactivating mutations in the Gulo gene have been identified in several non-synthesizing species (Cui et al, 2011b; Nishikimi et al, 1994; Nishikimi et al, 1992; Ohta and Nishikimi, 1999). We find Gulo inactivation in additional species (Figure S2) and show that Gulo is inactivated in all and only the sequenced non-synthesizers.…”