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Free keywords:
Animals
Biosynthetic Pathways/*genetics
Female
Gene Editing
Humans
Macaca/metabolism
Male
Metabolome/*genetics
Mice
Mice, Transgenic
Mutation, Missense
Neanderthals/*metabolism
Pan troglodytes/metabolism
Purines/*biosynthesis/*metabolism
*evolutionary biology
*human
*human evolution
*mouse
*neandertals
*purine biosynthesis
Abstract:
We analyze the metabolomes of humans, chimpanzees, and macaques in muscle, kidney and three different regions of the brain. Although several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution contributes to much or all of the reduction of de novo synthesis of purines in humans.
