title: Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.
abstract: Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bozek
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China; Graduate School of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Wei
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China; Graduate School of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jieyi
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Raik
authors.initials: R
authors.lastname: Pieszek
authors.affiliation: Department of Anthropology, The George Washington University, Washington DC, United States of America.
authors.forename: Chet C
authors.initials: CC
authors.lastname: Sherwood
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States of America.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: Alamogordo Primate Facility, Holloman AFB, Alamogordo, New Mexico, United States of America.
authors.forename: John J
authors.initials: JJ
authors.lastname: Ely
authors.affiliation: Max Planck Institute for Molecular Plant Physiology, Potsdam, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinhauser
authors.affiliation: Max Planck Institute for Molecular Plant Physiology, Potsdam, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Willmitzer
authors.affiliation: Department of Exercise and Sport Sciences, Section of Human Physiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Bangsbo
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, Malmö, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Hansson
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Josep
authors.initials: J
authors.lastname: Call
authors.affiliation: Max Planck Institute for Molecular Plant Physiology, Potsdam, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Giavalisco
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003071:Cognition / Q000502:physiology; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008251:Macaca / Q000378:metabolism* / Q000523:psychology; D008297:Male; D055442:Metabolome; D051379:Mice; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D002679:Pan troglodytes / Q000378:metabolism* / Q000523:psychology; D017397:Prefrontal Cortex / Q000378:metabolism*; D013045:Species Specificity