Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2consumption,
V̇O2max, during acute cold exposure) in high-altitude deer mice ( Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2transport pathway to examine the links between cardiorespiratory traits and V̇O2max. Results
Physiological experiments revealed that increases in Hb-O2affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in
V̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2affinity on V̇O2max in hypoxia was contingent on the capacity for O2diffusion in active tissues. Conclusions
These results suggest that increases in Hb-O2affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2affinity is contingent on the capacity to extract O2from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.