Submitted May 9, 2007
Accepted August 22, 2007
Acquired hematopoietic stem cell disorders and mammalian size
Joao V. Lopes, Jorge M Pacheco, and David Dingli*
Centro de Fisica Teorica e Computacional, & Departamento de Fisica da Faculdade de Ciencias, Universidade Lisboa, Lisboa, Portugal
Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, United States
Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, United States
* Corresponding author; email: dingli.david{at}mayo.edu.
Hematopoietic stem cells (HSC) can both self-renew and differentiate into precursors of all types of blood cells. HSC are divided into an active pool and a quiescent reserve. Cells selected for the active pool contribute to hematopoiesis for many years. Mutations in HSC can lead to neoplasms such as chronic myeloid leukemia although the risk of neoplastic HSC disorders varies across mammals. We use allometric scaling relations combined with mutation-selection evolutionary dynamics to determine which mammalian species is most resistant to HSC disorders. We find that the advantage of large mammals at escaping the selective pressure of cancer cells is insufficient to overcome the increased risk of acquiring mutations. Hence mutation dominates, which favors smaller stem cell pools and, consequently smaller mammals, since these minimize the development of mutations in the active stem cell pool. Consequently, the smaller the active stem cell pools the better.
