Reduced purine biosynthesis in humans after their divergence from Neandertals.

Autor:	Stepanova V; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation.; Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russian Federation., Moczulska KE; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Vacano GN; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States., Kurochkin I; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Ju X; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.; Okinawa Institute of Science and Technology, Onna-son, Japan., Riesenberg S; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Macak D; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Maricic T; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Dombrowski L; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Schörnig M; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany., Anastassiadis K; Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technical University Dresden, Dresden, Germany., Baker O; Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technical University Dresden, Dresden, Germany., Naumann R; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany., Khrameeva E; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Vanushkina A; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Stekolshchikova E; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Egorova A; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Tkachev A; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Mazzarino R; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States., Duval N; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States., Zubkov D; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Giavalisco P; Max Planck Institute for Biology of Ageing, Cologne, Germany., Wilkinson TG; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States., Patterson D; The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States., Khaitovich P; Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation., Pääbo S; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.; Okinawa Institute of Science and Technology, Onna-son, Japan.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 May 04; Vol. 10. Date of Electronic Publication: 2021 May 04.
DOI:	10.7554/eLife.58741
Abstrakt:	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. Competing Interests: VS, KM, GV, IK, XJ, SR, DM, TM, LD, MS, KA, OB, RN, EK, AV, ES, AE, AT, RM, ND, DZ, PG, TW, DP, PK, SP No competing interests declared (© 2021, Stepanova et al.)
Databáze:	MEDLINE
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