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B."],"published-print":{"date-parts":[[2018,9,12]]},"abstract":"<jats:p>Compared to other primates, humans are exceptional long-distance runners, a feature that emerged in genus<jats:italic>Homo<\/jats:italic>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 (<jats:italic>CMAH<\/jats:italic>) gene also became fixed in our ancestral lineage.<jats:italic>Cmah<\/jats:italic>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<jats:italic>Cmah<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>mice and observed an increased performance during forced treadmill testing and after 15 days of voluntary wheel running.<jats:italic>Cmah<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>hindlimb muscle exhibited more capillaries and a greater fatigue resistance<jats:italic>in situ<\/jats:italic>. Maximal coupled respiration was also higher in<jats:italic>Cmah<\/jats:italic>null mice<jats:italic>ex vivo<\/jats:italic>and relevant differences in metabolic pathways were also noted. Taken together, these data suggest that<jats:italic>CMAH<\/jats:italic>loss contributes to an improved skeletal muscle capacity for oxygen use. If translatable to humans,<jats:italic>CMAH<\/jats:italic>loss could have provided a selective advantage for ancestral<jats:italic>Homo<\/jats:italic>during the transition from forest dwelling to increased resource exploration and hunter\/gatherer behaviour in the open savannah.<\/jats:p>","DOI":"10.1098\/rspb.2018.1656","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T08:06:23Z","timestamp":1536739583000},"page":"20181656","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Human-like Cmah inactivation in mice increases running endurance and decreases muscle fatigability: implications for human evolution"],"prefix":"10.1098","volume":"285","author":[{"given":"Jonathan","family":"Okerblom","sequence":"first","affiliation":[{"name":"Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Glycobiology Research and Training Center (GRTC), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Fletes","sequence":"additional","affiliation":[{"name":"Glycobiology Research and Training Center (GRTC), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Initiative for Maximizing Student Development (IMSD) Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemal H.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Schenk","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-975X","authenticated-orcid":false,"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Glycobiology Research and Training Center (GRTC), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen C.","family":"Breen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2018,9,12]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190683"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/366261a0"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/385333a0"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03052"},{"key":"e_1_3_7_6_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/j.2040-4603.2015.tb00602.x","article-title":"Human locomotion and heat loss: an evolutionary perspective","volume":"5","author":"Lieberman DE","year":"2015","journal-title":"Compr. 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