The evolution of vitamin C biosynthesis and transport in animals

Abstract

Background Vitamin C (VC) is an indispensable antioxidant and co-factor for optimal function and development of eukaryotic cells. In animals, VC can be synthesized by the organism, acquired through the diet, or both. In the single VC synthesis pathway described in animals, the penultimate step is catalysed by Regucalcin, and the last step by l-gulonolactone oxidase (GULO). The GULO gene has been implicated in VC synthesis only, while Regucalcin has been shown to have multiple functions in mammals. Results Both GULO and Regucalcin can be found in non-bilaterian, protostome and deuterostome species. Regucalcin, as here shown, is involved in multiple functions such as VC synthesis, calcium homeostasis, and the oxidative stress response in both Deuterostomes and Protostomes, and in insects in receptor-mediated uptake of hexamerin storage proteins from haemolymph. In Insecta and Nematoda, however, there is no GULO gene, and in the latter no Regucalcin gene, but species from these lineages are still able to synthesize VC, implying at least one novel synthesis pathway. In vertebrates, SVCT1, a gene that belongs to a family with up to five members, as here shown, is the only gene involved in the uptake of VC in the gut. This specificity is likely the result of a subfunctionalization event that happened at the base of the Craniata subphylum. SVCT-like genes present in non-Vertebrate animals are likely involved in both VC and nucleobase transport. It is also shown that in lineages where GULO has been lost, SVCT1 is now an essential gene, while in lineages where SVCT1 gene has been lost, GULO is now an essential gene. Conclusions The simultaneous study, for the first time, of GULO, Regucalcin and SVCTs evolution provides a clear picture of VC synthesis/acquisition and reveals very different selective pressures in different animal taxonomic groups.

Advances in Novel Animal Vitamin C Biosynthesis Pathways and the Role of Prokaryote-Based Inferences to Understand Their Origin

“…In addition, a comprehensive search for homologs of the enzymatic constituents of the plant and animal VC synthesis pathways in C. elegans was also performed, revealing that no pathway was present as a complete set [ 115 ]. The loss of the GULO and Regucalcin , is also observed in other nematode species [ 118 ]. Given the evidence, it was suggested that VC synthesis in C. elegans likely occurs through a yet undescribed metabolic pathway [ 115 ].…”

“…A direct involvement of Dca or Regucalcin in VC synthesis would imply that at least the lactonase component of the animal pathway is conserved in D. melanogaster . Using an in silico methodology, both Regucalcin and Dca were inferred to be involved in calcium homeostasis and in the oxidative stress response, but so far, no evidence was found for its involvement in VC synthesis [ 118 ]. The involvement in the calcium homeostasis and in the oxidative stress response are expected given the multiple functions of Regucalcin in vertebrates (reviewed in [ 133 ]).…”

“…The involvement in the calcium homeostasis and in the oxidative stress response are expected given the multiple functions of Regucalcin in vertebrates (reviewed in [ 133 ]). The inference of a divergent protein interaction surface at Dca in comparison with Regucalcin, along with the detection of positively selected amino acids near and within the active site region, suggests that Dca might have also acquired novel functions involving its lactonase activity and overall contribution to protein complexes [ 118 ]. The constitutive suppression, under the actin 5C driver, of either Regucalcin or Dca in D. melanogaster, did not clarify the role of these genes in VC synthesis [ 118 ].…”

“…The inference of a divergent protein interaction surface at Dca in comparison with Regucalcin, along with the detection of positively selected amino acids near and within the active site region, suggests that Dca might have also acquired novel functions involving its lactonase activity and overall contribution to protein complexes [ 118 ]. The constitutive suppression, under the actin 5C driver, of either Regucalcin or Dca in D. melanogaster, did not clarify the role of these genes in VC synthesis [ 118 ]. Indeed, both genes are required for D. melanogaster viability, since in both cases over 70% of the individuals with suppressed expression were only able to reach the pupal stage [ 118 ], and thus the biological processes in which they are involved could not be determined.…”

“…The constitutive suppression, under the actin 5C driver, of either Regucalcin or Dca in D. melanogaster, did not clarify the role of these genes in VC synthesis [ 118 ]. Indeed, both genes are required for D. melanogaster viability, since in both cases over 70% of the individuals with suppressed expression were only able to reach the pupal stage [ 118 ], and thus the biological processes in which they are involved could not be determined. The reduced viability could be attributed, for instance, to the dysregulation of calcium homeostasis/signaling, as stated in [ 118 ].…”