Hematopoiesis as a competitive exclusion process: Estimation of a stem cell selective advantage

Female Safari cats are offspring of domestic and Geoffroy parents, and are balanced heterozygotes with equal numbers of Blood cells containing domestic and 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 in cats aged 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 of the distribution of phenotype in samples taken during the second stage of hematopoiesis (Blood cell production), we estimate, through simulation and mathematical calculation, the Geoffroy selective advantages necessary to reproduce the data obtained from female Safari cats. It is shown 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.