Who Needs Vitamin C? “Vitamin C is unique…as its essentiality as a nutrient is restricted to only a limited number of exceptional species among phylogenetically higher animals. In other words, nearly all higher animals can synthesize vitamin C…” 1991

Scurvy R.I.P. Vitamin C

A treatise of the scurvy, 1753 James Lind (1716 – 1799) “…the most sudden and visible good effects were perceived from the use of the oranges and lemons; one of those who had taken them, being at the end of six days fit for duty.” A treatise of the scurvy, 1753

Evolution is Testable Scurvy, Vitamin C, and Common Ancestry 1933: Vitamin C identified and described. 1934: Vitamin C artificially synthesized. 1913: Scurvy occurs in other primates. 1957: Scurvy due to lack of enzyme. 1907: Scurvy occurs in guinea pigs. 1907 Scurvy occurs in guinea pigs. 1913 Scurvy occurs in other primates. 1933 Vitamin C identified and described. 1934 Vitamin C artificially synthesized. 1957 Scurvy due to lack of enzyme. Guinea Pigs Chimpanzees Orangutans Monkeys Tarsiers Gibbons Gorillas

Vitamin C Production enzyme 1 enzyme 2 enzyme 3 enzyme 4 “GULO” “VITAMIN C” D-GLUCOSE D-GLUCURONIC ACID D-GLUCURONIC ACID LACTONE L-GULONO- LACTONE 2-KETO-GULONO- GAMMA-LACTONE L-ASCORBIC ACID Prediction: If the ancestors of humans, other higher primates, and guinea pigs originally had the ability to synthesize vitamin C, then each of these species should carry evidence of this lost ability in their genes.

1 2 3 4 TACCCCGTGGAGGTACGCTTCACTCGCGGGGACGACATCCTGCTGAGCCCC GULO-related sequence comparison from exon X COW GUINEA PIG MACAQUE ORANG CHIMP HUMAN TACCCCGTGGAGGTACGCTTCACTCGCGGGGACGACATCCTGCTGAGCCCC TACCCTGTGGGGGTGCGCTTCACCCGGGGGGACGACATCCTGCTGAGCCCC TAACCGGTGGGGGTGCGCTTCACCCAAGG-GATGACATCATACTGAGCCCC TACCCGGTGGGGGTGCGCTTCACCCAGAG-GATGACGTCCTACTGAGCCCC TACCTGGTGGGGCTACGCTTCACCTGGAG-GATGACATCCTACTGAGCCCC TACCTGGTGGGGGTACGCTTCACCTGGAG-GATGACATCCTACTGAGCCCC GATGACATCATACTGAGCCCC GATGACGTCCTACTGAGCCCC GATGACATCCTACTGAGCCCC premature STOP codons TGA GULO-related sequence comparison from exon III COW GUINEA PIG CACTCGCCCTCAGACATCGCCTGCACTGACGGCTTCATGATCCACATGGGC CACTCCCCCTCCGACATTGCCTGAACAGAGGGCATCATGATCCACAGGGGC premature STOP codon TGA enzyme 1 enzyme 2 enzyme 3 enzyme 4 “GULO” 2-KETO-GULONO- GAMMA-LACTONE L-ASCORBIC ACID STOP D-GLUCOSE D-GLUCURONIC ACID D-GLUCURONIC ACID LACTONE L-GULONO- LACTONE

Deactivation of GULO enzyme Human Chimpanzee Orangutan Macaque Guinea Pig Cow Deactivation of GULO enzyme