Reduced purine biosynthesis in humans after their divergence from neandertals

Vita Stepanova, Kaja Ewa Moczulska, Guido N. Vacano, Ilia Kurochkin, Xiangchun Ju, Stephan Riesenberg, Dominik Macak, Tomislav Maricic, Linda Dombrowski, Maria Schörnig, Konstantinos Anastassiadis, Oliver Baker, Ronald Naumann, Ekaterina Khrameeva, Anna Vanushkina, Elena Stekolshchikova, Alina Egorova, Anna Tkachev, Randall Mazzarino, Nathan DuvalDmitri Zubkov, Patrick Giavalisco, Terry G. Wilkinson, David Patterson, Philipp Khaitovich, Svante Pääbo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere58741
JournaleLife
Volume10
DOIs
Publication statusPublished - May 2021
Externally publishedYes

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