A Genome Scan for Positive Selection in Thoroughbred Horses

Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1) deviations from expected heterozygosity (Ewens-Watterson test) in Thoroughbred (n = 112) and (2) global differentiation among four geographically diverse horse populations (FST). We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01), insulin receptor signalling (5.0-fold enrichment; P<0.01) and lipid transport (2.2-fold enrichment; P<0.05) genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05) and focal adhesion pathway (1.9-fold enrichment; P<0.01) genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1), ACTA1 (actin, alpha 1, skeletal muscle), ACTN2 (actinin, alpha 2), ADHFE1 (alcohol dehydrogenase, iron containing, 1), MTFR1 (mitochondrial fission regulator 1), PDK4 (pyruvate dehydrogenase kinase, isozyme 4) and TNC (tenascin C). Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes within the complex molecular networks underlying obesity and its consequential pathologies, such as type 2 diabetes. Therefore, we propose Thoroughbred as a novel in vivo large animal model for understanding molecular protection against metabolic disease

Oxygen transport during exercise in large mammals. II. Oxygen uptake by the pulmonary gas exchanger

Because the maximal rate of O2 consumption (VO2max) of the horse is 2.6 times larger than that of steers of equal size, we wondered whether their pulmonary gas exchanger is proportionately larger. Three Standardbred racehorses [body mass (Mb) = 447 kg] and three domestic steers (Mb = 474 kg) whose cardiovascular function at VO2max had been thoroughly studied (Jones et al. J. Appl. Physiol. 67: 862–870, 1989) were used to study their lungs by morphometry. The basic morphometric parameters were similar in both species. The nearly 2 times larger lung volumes of the horses caused the gas exchange surfaces and capillary blood volume to be 1.6 to 1.8 times larger. Morphometric pulmonary diffusing capacity was 2 times larger in the horse than in the steer; the 2.6-fold greater rate of O2 uptake thus required the alveolar-capillary PO2 difference to be 1.3 times larger in the horse than in the steer. Combining physiological and morphometric data, we calculated capillary transit time at VO2max to be 0.4–0.5 s. Bohr integration showed capillary blood to be equilibrated with alveolar air after 75 and 58% of transit time in horses and steers, respectively; horses maintain a smaller degree of redundancy in their pulmonary gas exchanger.</p

Smaller is better—but not too small: A physical scale for the design of the mammalian pulmonary acinus

The transfer of oxygen from air to blood in the lung involves three processes: ventilation through the airways, diffusion of oxygen in the air phase to the alveolar surface, and finally diffusion through tissue into the capillary blood. The latter two steps occur in the acinus, where the alveolar gas-exchange surface is arranged along the last few generations of airway branching. For the acinus to work efficiently, oxygen must reach the last branches of acinar airways, even though some of it is absorbed along the way. This “screening effect” is governed by the relative values of physical factors like diffusivity and permeability as well as size and design of the acinus. Physics predicts that efficient acini should be space-filling surfaces and should not be too large. It is shown that the mammalian acini fulfill these requirements, small mammals being more efficient than large ones both at rest and in exercise