Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

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Katarzyna Bozek, Yuning Wei, Zheng Yan, Xiling Liu, Jieyi Xiong, Masahiro Sugimoto, Masaru Tomita, Svante Pääbo, Raik Pieszek, Chet C Sherwood, Patrick R Hof, John J Ely, Dirk Steinhauser, Lothar Willmitzer, Jens Bangsbo, Ola Hansson, Josep Call, Patrick Giavalisco, Philipp Khaitovich

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.

Original languageEnglish
Article numbere1001871
JournalP L o S Biology
Volume12
Issue number5
Number of pages14
ISSN1544-9173
DOIs
Publication statusPublished - 2014

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