Phylogeny and evolution of erythrocytes in mammals

In the past century, several authors have investigated the allometry of haematological parameters in mammals. As haematocrit and haemoglobin (Hb) concentration are almost constant within the Mammalia (although with notable exceptions), differences in other haematological parameters are mainly reducible to red blood cell size (mean corpuscular volume, MCV). Past studies testing for correlation between MCV and body mass have given contradictory results. Using phylogenetically informed regressions, here I demonstrate that the correlation between MCV and body mass is indirect, and is in reality due to the correlation between MCV and basal metabolic rate. 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 that predicted by their metabolic rate, while Ruminantia show the inverse. Interestingly, these species show the highest and lowest, respectively, Hb affinity for oxygen. In the present paper, I suggest that Hb-oxygen affinity, acting as a biological constraint for oxygen exchange, determines the size of red blood cells. Hb intrinsic affinity for oxygen shows little variation during evolution and modifying the levels of allosteric factors can be viewed as an adaption to adjust Hb-oxygen affinity to metabolic demands (the same also happens during ontogeny). Nonetheless, in some lineages, mutations raising Hb-oxygen affinity allowed some species to colonize hypoxic environments; in Ruminantia, instead, there was a drastic decrease, which cannot be adaptively explained.