Phylogeny and Evolution of Erythrocytes in Mammals

In the past century, several authors investigated the allometry of hematological parameters in mammals. Since hematocrit and hemoglobin concentration are almost constant within the Mammalia (although with notable exceptions), differences in other hematological parameters are mainly reducible to red blood cell size (MCV). Past studies testing for correlation between MCV and body mass have given contradictory results. Using phylogenetically-informed regressions, here is demonstrated that correlation between MCV and body mass is indirect, and is in reality due to correlation between MCV and basal metabolic rates. This could be explained by the fact that small erythrocytes allow a fast release of oxygen in tissues with high metabolic demand. Nonetheless, hypoxia-adapted species show MCV greater than those predicted by their metabolic rates, while Ruminantia show the inverse. Interestingly, these species show the highest and lowest, respectively, hemoglobin affinity for oxygen. In the present paper, it is suggested that hemoglobin affinity, acting as a biological constrain for oxygen exchange, determines the size of red blood cells. Hemoglobin intrinsic affinity showed little variations during evolution and modifying the levels of allosteric factors can be viewed as an adaption to adjust hemoglobin affinity to metabolic demands (the same happens also during ontogeny). Nonetheless, in some lineages, mutations raising hemoglobin affinity allowed some species to colonize hypoxic environments; in Ruminantia, instead, there was a drastic decrease, which cannot be adaptively explained.