Evolutionary Pressures Behind the Translocation of Hematopoiesis to the Bone Marrow Cavity in Terrestrial Vertebrates

Nearly 400 million years ago, vertebrate life began to transition from a purely aquatic existence to the terrestrial environment. Concurrently, exposure to ionizing radiation from cosmic and geologic sources increased substantially. Around the same time, vertebrate hematopoietic stem cells (HSCs) migrated from the liver and peri-nephric parts of the abdomen into the interior of bones. Interestingly, among today's vertebrates, only fish lack bone marrow. All other extant vertebrates maintain their HSCs in the bone marrow cavity. We propose protection from sub-lethal DNA damage to these long-lived radiation-sensitive cells because of exposure to ionizing radiation is why HSCs are sequestered with the bone marrow cavity. Our calculations support this hypothesis. Residence in the bone marrow cavity reduced exposure to penetrating background radiation and the concomitant DNA damage by at least 20%. This reduction was even more significant radio-biologically when considering the relatively hypoxic conditions within the bone marrow cavity and oxygen's role in enhancing radiogenic DNA damage. This may be particularly relevant considering the oxygen-rich atmosphere in existence at the time of transitioning to a terrestrial habitat. Given the exquisite sensitivity of HSCs and proliferating blood cells to radiation, we propose this translocation provided a selective advantage and that protection from sub-lethal radiogenic DNA damage at least partially explains translocation of hematopoietic cells to the bone marrow cavity in terrestrial vertebrates.