Title: Mitochondria and male disease; somatic mosaicism; infective dose
Department of Ecology & Evolutionary Biology
Three simple processes profoundly influence the nature of disease
(1) Mitochondria typically transmit through the female line. Mutations that cause disease in males and are nearly neutral in females drift in frequency. That sex-biased selective sieve predicts a widespread association between mitochondria and male disease.
(2) A human body has about 100 trillion cells derived from the single zygote. The vast number of cell divisions introduce many mutations, causing widespread somatic mosaicism. Theory predicts great diversity in mosaicism between individuals. That mosaic diversity may explain a significant fraction of the variance in predisposition to disease.
(3) The mechanisms of initial pathogen invasion may explain variation in infective dose. Virulence factors directly injected into neighboring host cells require few initial pathogens to start an infection. Virulence factors that act distantly on host immune regulation require many initial pathogens to generate a sufficient concentration of diffusible factors. Local versus global virulence factor action may correspond to small versus large minimum infective dose.
New genomic technology provides opportunities to test these predictions. Recent empirical studies show the expanding importance of each topic.