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1.  Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness 
PLoS Biology  2014;12(5):e1001871.
Accelerated evolution of the human brain and muscle metabolomes reflects our unique cognitive and physical capacities.
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.
Author Summary
Physiological processes that maintain our tissues' functionality involve the generation of multiple products and intermediates known as metabolites—small molecules with a weight of less than 1,500 Daltons. Changes in concentrations of these metabolites are thought to be closely related to changes in phenotype. Here, we assessed concentrations of more than 10,000 metabolites in three brain regions and two non-neural tissues (skeletal muscle and kidney) of humans, chimpanzees, macaque monkeys, and mice using mass spectrometry-based approaches. We found that the evolution of the metabolome largely reflects genetic divergence between species and is not greatly affected by environmental factors. In the human lineage, however, we observed an exceptional acceleration of metabolome evolution in the prefrontal cortical region of the brain and in skeletal muscle. Based on additional behavioral tests, we further show that metabolic changes in human muscle seem to be paralleled by a drastic reduction in muscle strength. The observed rapid metabolic changes in brain and muscle, together with the unique human cognitive skills and low muscle performance, might reflect parallel mechanisms in human evolution.
doi:10.1371/journal.pbio.1001871
PMCID: PMC4035273  PMID: 24866127
2.  Cetaceans Have Complex Brains for Complex Cognition 
PLoS Biology  2007;5(5):e139.
A group of eminent cetacean researchers respond to headlines charging that dolphins might be "flippin' idiots". They examine behavioural, anatomical and evolutionary data to conclude that the large brain of cetaceans evolved to support complex cognitive abilities.
doi:10.1371/journal.pbio.0050139
PMCID: PMC1868071  PMID: 17503965

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