a model-based bayesian estimation of the rate of evolution of vntr loci in mycobacterium tuberculosis基于模型的贝叶斯估计的速度进化的vntr基因座在结核分枝杆菌.pdfVIP

A Model-Based Bayesian Estimation of the Rate of Evolution of VNTR Loci in Mycobacterium tuberculosis 1,2 3 1 2 R. Zachariah Aandahl , Josephine F. Reyes , Scott A. Sisson , Mark M. Tanaka * 1 School of Mathematics and Statistics, University of New South Wales, Sydney, New South Wales, Australia, 2 Evolution Ecology Research Centre and School of Biotechnology Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia, 3 The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia Abstract Variable numbers of tandem repeats (VNTR) typing is widely used for studying the bacterial cause of tuberculosis. Knowledge of the rate of mutation of VNTR loci facilitates the study of the evolution and epidemiology of Mycobacterium tuberculosis. Previous studies have applied population genetic models to estimate the mutation rate, leading to estimates varying widely from around 10{5 to 10{2 per locus per year. Resolving this issue using more detailed models and statistical methods would lead to improved inference in the molecular epidemiology of tuberculosis. Here, we use a model-based approach that incorporates two alternative forms of a stepwise mutation process for VNTR evolution within an epidemiological model of disease transmission. Using this model in a Bayesian framework we estimate the mutation rate of VNTR in M. tuberculosis from four published data sets of VNTR profiles from Albania, Iran, Morocco and Venezuela. In the first variant, the mutation rate increases linearly with respect to repeat numbers (linear model); in the second, the mutation rate is constant across repeat numbers (cons