Hematopoiesis as a Competitive Exclusion Process

Female Safari cats are offspring of domestic and Geoffroy parents, and are balanced helcer,oz,rgc,tes with equal numbers of blood cells containing domestic as Geoffroy-type glucose 6-phosphate dehydrogenase (G6PD), an X-chromosome derived enzyme. In previous studies, however, we observed increasing percentages of blood cells with Geoffroy G6PD over 4-12 years. Similarly, ratios of parental X-chromosome phenotypes greater than three to one are common in women over age 60, while women under 40 typically exhibit one to one ratios. Using a two-compartment hidden-Markov model to represent the first two stages of hematopoiesis, the process of blood cell production, we show through simulation and mathematical calculation that small differences in the kinetics of hematopoietic stem cells (HSC), less than might be detected by in vitro assays, can explain the "clonal dominance" observed with aging in cats, and by extension, human females. Conceptually, hematopoiesis in females can be viewed as a competitive exclusion process in which two populations of HSC (defined by parental X-chromosome phenotype) compete for environmental resources. As in many ecological examples, dominance may occur only after long periods of time.