The genetics of vitamin C loss in vertebrates

Abstract

Vitamin C (ascorbic acid) plays important roles as an anti-oxidant and in collagen synthesis. These important roles, and the relatively large amounts of vitamin C required daily, likely explain why most vertebrate species are able to synthesize this compound. Surprisingly, many species, such as teleost fishes, anthropoid primates, guinea pigs, as well as some bat and Passeriformes bird species, have lost the capacity to synthesize it. Here, we review the genetic bases behind the repeated losses in the ability to synthesize vitamin C as well as their implications. In all cases so far studied, the inability to synthesize vitamin C is due to mutations in the L-gulono-γ-lactone oxidase (GLO) gene which codes for the enzyme responsible for catalyzing the last step of vitamin C biosynthesis. The bias for mutations in this particular gene is likely due to the fact that losing it only affects vitamin C production. Whereas the GLO gene mutations in fish, anthropoid primates and guinea pigs are irreversible, some of the GLO pseudogenes found in bat species have been shown to be reactivated during evolution. The same phenomenon is thought to have occurred in some Passeriformes bird species. Interestingly, these GLO gene losses and reactivations are unrelated to the diet of the species involved. This suggests that losing the ability to make vitamin C is a neutral trait.

Keywords: Ascorbic acid; GLO gene; L-gulono-gamma-lactone oxidase; biosynthesis; pseudogene; vitamin C..

Fig. (1)

Biochemical pathway of vitamin C synthesis in vertebrates. Numbers represent the following enzymes: 1. UDP-glucose pyrophosphorylase (EC 2.7.7.9), 2. UDP-glucose dehydrogenase (EC 1.1.1.22), 3. UDP-glucuronidase (EC 3.2.1.31), 4. Glucoronate reductase (EC 1.1.1.19), 5. Gluconolactonase (EC 3.1.1.17), 6. L-gulonolactone oxidase (GLO, EC 1.1.3.8), 7. L-gulonate 3-dehydrogenase (EC 1.1.1.45). This figure is based on information from references [16, 56].

Fig. (2)

Phylogenetic distribution of the ability to synthesize vitamin C in cartilaginous and bony fishes. Lineages able to synthesize vitamin C are in black, those incapable are in gray. The phylogenetic relationships are based on those in references [24, 26]. The complete species list, species names and references are given in Supplemental Table 1.

Fig. (3)

Phylogenetic distribution of the ability to synthesize vitamin C in mammals. Lineages able to synthesize vitamin C are in black, those incapable are in gray. The phylogenetic relationships are based on those in reference [63]. The complete species list, species names and references are given in Supplemental Table 2.

Fig. (4)

Schematic representations (not to scale) of the GLO gene structure in anthropoid primates and in guinea pigs. Black boxes represent exons that are still found in the genome of these species whereas white boxes with an X represent deleted exons or exon parts. Numbering refers to the exon numbers.

Fig. (5)

Phylogenetic distribution of the ability to synthesize vitamin C in bats. Lineages able to synthesize vitamin C are in black, those incapable are in gray. The phylogenetic relationships are based on those in reference [64]. The complete species list, species names and references are given in Supplemental Table 3.

Fig. (6)

Phylogenetic distribution of the ability to synthesize vitamin C in birds. Lineages able to synthesize vitamin C are in black, those incapable are in gray and empty branches represent ancestral lineages where the status of vitamin C production is not known. The phylogenetic relationships are based on those in reference [40] and the start (*) next to the Terpsiphone genus indicates that it is now known to belong to the Corvidea family. The complete species list, species names and references are given in Supplemental Table 4.