Reduced purine biosynthesis in humans after their divergence from Neandertals

eLife

Oliver Baker¹  Konstantinos Anastassiadis¹  Patrick Giavalisco²  Dominik Macak³  Kaja Ewa Moczulska³  Linda Dombrowski³  Stephan Riesenberg³  Tomislav Maricic³  Maria Schörnig³  Xiangchun Ju⁴  Svante Pääbo⁴  Ronald Naumann⁵  Alina Egorova⁶  Anna Vanushkina⁶  Ekaterina Khrameeva⁶  Anna Tkachev⁶  Elena Stekolshchikova⁶  Philipp Khaitovich⁶  Dmitri Zubkov⁶  Ilia Kurochkin⁶  Vita Stepanova⁷  Randall Mazzarino⁸  Nathan Duval⁸  David Patterson⁸  Terry G Wilkinson⁸  Guido N Vacano⁸ 

[1] Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technical University Dresden, Dresden, Germany;Max Planck Institute for Biology of Ageing, Cologne, Germany;Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany;Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany;Okinawa Institute of Science and Technology, Onna-son, Japan;Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation;Skolkovo Institute for Science and Technology, Skolkovo, Russian Federation;Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russian Federation;The Eleanor Roosevelt Institute and Knoebel Institute for Healthy Aging, University of Denver, Denver, United States;

关键词: human evolution;    neandertals;    purine biosynthesis;    Human;    Mouse;   

DOI  :  10.7554/eLife.58741

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY