Biochemical and physiological correlates of deer mouse alpha-chain hemoglobin polymorphisms.

The alpha-hemoglobin chains in adult deer mice are usually encoded by two tightly linked loci. Because of strong linkage disequilibrium, almost all alpha-globin haplotypes fall into just two classes. The a0c0 class predominates in high-altitude populations, whereas the a1c1 class is generally fixed in low-altitude populations. Here we show that the alpha-globin genotype has effects at both the biochemical level [on blood oxygen affinity (P50)]and at the level of whole-animal physiology [on maximum rate of oxygen consumption (VO2max) during both exercise and cold exposure]. The a1c1/a1c1 genotype mice have the highest P50 values and show the highest Vo2max values at low altitude (340 m) but the lowest VO2max values at high altitude (3800 m). The a0c0/a0c0 mice have the lowest P50, and show the highest VO2max at high altitude but usually have the lowest VO2max at low altitude. The a0c0/a1c1 heterozygotes have an intermediate P50 and are generally intermediate in VO2max at both altitudes. Since high VO2max is advantageous for aerobic exercise and thermogenesis, the physiological data provide a potential explanation for the correlation of haplotype frequencies with altitude.