@article {317245, title = {Human-like Cmah Inactivation in Mice Increases Running Endurance and Decreases Muscle Fatigability: Implications for Human Evolution}, journal = {Proceedings of the Royal Society (Biological Sciences)}, volume = {285}, year = {2018}, month = {09/2018}, 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\ Homoduring the transition from forest dwelling to increased resource exploration and hunter/gatherer behaviour in the open savannah.

}, doi = {10.1098/rspb.2018.1656}, url = {http://rspb.royalsocietypublishing.org/content/285/1886/20181656}, author = {Okerblom, JJ and Fletes, W and Patel, HH and Schenk, S and Ajit Varki and Breen, EC} }