Okerblom 2018 Proc Biol Sci

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Okerblom J, Fletes W, Patel HH, Schenk S, Varki A, Breen EC (2018) Human-like Cmah inactivation in mice increases running endurance and decreases muscle fatigability: implications for human evolution. Proc Biol Sci 285:20181656.

» PMID: 30209232

Okerblom J, Fletes W, Patel HH, Schenk S, Varki A, Breen EC (2018) Proc Biol Sci

Abstract: Compared to other primates, humans are exceptional long-distance runners, a feature that emerged in genus Homo approximately 2 Ma and is classically attributed to anatomical and physiological adaptations such as an enlarged gluteus maximus and improved heat dissipation. However, no underlying genetic changes have currently been defined. Two to three million years ago, an exon deletion in the CMP-Neu5Ac hydroxylase (CMAH) gene also became fixed in our ancestral lineage. Cmah loss in mice exacerbates disease severity in multiple mouse models for muscular dystrophy, a finding only partially attributed to differences in immune reactivity. We evaluated the exercise capacity of Cmah-/- mice and observed an increased performance during forced treadmill testing and after 15 days of voluntary wheel running. Cmah-/- hindlimb muscle exhibited more capillaries and a greater fatigue resistance in situ Maximal coupled respiration was also higher in Cmah null mice ex vivo and relevant differences in metabolic pathways were also noted. Taken together, these data suggest that CMAH loss contributes to an improved skeletal muscle capacity for oxygen use. If translatable to humans, CMAH loss could have provided a selective advantage for ancestral Homo during the transition from forest dwelling to increased resource exploration and hunter/gatherer behaviour in the open savannah.

Keywords: Evolution, Human, Hunting, Running Bioblast editor: Plangger M O2k-Network Lab: US CA San Diego Patel HH, US CA San Diego Schenk S


Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

2018-10