ON THE 3 METHODS FOR ESTIMATING DELETERIOUS GENOMIC MUTATION PARAMETERS

Due to the tremendous cost of the traditional mutation-accumulation ap proach (the Bateman-Mukai technique), data are rare for deleterious mu tation parameters such as genomic mutation rate, selection and dominan ce coefficients. Two alternative approaches have been developed (the M orton-Charlesworth and Deng-Lynch techniques). Except for the Deng-Lyn ch method, the statistical properties (bias and sampling variance) of these techniques are poorly understood; therefore we investigated them using computer simulation. With constant fitness effects of mutations , the Bateman-Mukai (assuming additive effects) and Deng-Lynch (assumi ng multiplicative effects) techniques are unbiased; the Morton-Charles worth technique (assuming multiplicative effects) is very biased if fi tness is used in the regression to estimate h, but slightly biased if the logarithm of fitness is used. With variable fitness effects, all t echniques are biased. The Deng-Lynch technique is statistically better than the others except when fitness is used to estimate the average d egree of dominance in selfing populations with the Morton-Charlesworth technique. If fitness effects are multiplicative but additivity is as sumed, the Bateman-Mukai technique is biased under constant fitness ef fects, and less biased under variable fitness effects relative to when fitness effects are additive (as assumed by the technique). Our study not only quantifies the degree of bias under the biologically plausib le situations investigated, thus forming a basis for correct inference of the true parameters by using these techniques, but also provides i nsights into the relative efficiencies of these techniques when the sa me number of genotypes are handled experimentally.