The adaptive benefit of evolved increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice

Jonathan P Velotta,Natalia Gutiérrez-Pinto,Chandrasekhar Natarajan,Oliver H Wearing,Catherine M Ivy,Shane C Campbell-Staton,Zachary A Cheviron,Jay F Storz,Graham R Scott

doi:10.1186/s12915-021-01059-4

Abstract

BackgroundComplex 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 O2 consumption, V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2 inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2 affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2 transport pathway to examine the links between cardiorespiratory traits and V̇O2max.ResultsPhysiological experiments revealed that increases in Hb-O2 affinity 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-O2 affinity on V̇O2max in hypoxia was contingent on the capacity for O2 diffusion in active tissues.ConclusionsThese results suggest that increases in Hb-O2 affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2 diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2 affinity is contingent on the capacity to extract O2 from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.

Highlights

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 measured thermogenic V O2max, arterial O2 saturation, and other cardiorespiratory traits in vivo during acute exposure to cold heliox in normoxia (21% O2) and hypoxia (12% O2) in male and female F2 hybrid mice that possessed a diverse array of different α- and β-globin genotypes
We describe the effects of Hb genotype on thermogenic V O2max and hematological traits in mice acclimated to normoxia, and we describe how Hb genotype affects acclimation responses to chronic hypoxia

Summary

Introduction

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 O2 consumption, VO2max, during acute cold exposure) in highaltitude deer mice (Peromyscus maniculatus). The capacity for aerobic thermogenesis in small mammals at high altitude is a complex performance trait that is well suited to experimental studies of how patterns of phenotypic integration affect the process of adaptation. Aerobic thermogenesis (quantified as maximal O2 consumption, V O2max, during acute cold exposure) in hypoxia is under strong directional selection in some small mammals at high altitude [4], which have evolved higher thermogenic V O2max [5,6,7,8,9]. Studies of thermogenic V O2max in highaltitude natives are ideal for understanding the mechanisms underlying the adaptive evolution of complex traits

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