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 Duval, Dmitri Zubkov, Patrick Giavalisco, Terry G Wilkinson, David Patterson, Philipp Khaitovich, Svante Pääbo
Skolkovo Institute for Science and Technology, Russian Federation; Institute for Information Transmission Problems, Russian Academy of Sciences, Russian Federation; Max Planck Institute for Evolutionary Anthropology, Germany; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, United States; Okinawa Institute of Science and Technology, Japan; Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technical University Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Germany; Max Planck Institute for Biology of Ageing, Germany
Research Article May 4, 2021 Cite as: eLife 2021;10:e58741 DOI: 10.7554/eLife.58741
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.
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