Dataset Information

Frequent adaptation and the McDonald-Kreitman test.

ABSTRACT: Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection (?) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates of ? severely underestimate the true rate of adaptation even if all polymorphisms with population frequencies under 50% are excluded. Furthermore, already under intermediate rates of adaptation, genetic draft substantially distorts the site frequency spectra at neutral and functional sites from the expectations under mutation-selection-drift balance. MK-type approaches that first infer demography from synonymous sites and then use the inferred demography to correct the estimation of ? obtain almost the correct ? in our simulations. However, these approaches typically infer a severe past population expansion although there was no such expansion in the simulations, casting doubt on the accuracy of methods that infer demography from synonymous polymorphism data. We propose a simple asymptotic extension of the MK test that yields accurate estimates of ? in our simulations and should provide a fruitful direction for future studies.

SUBMITTER: Messer PW

PROVIDER: S-EPMC3666677 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Frequent adaptation and the McDonald-Kreitman test.

Messer Philipp W PW Petrov Dmitri A DA

Proceedings of the National Academy of Sciences of the United States of America 20130506 21

Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection (α) from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimat ...[more]

PMID: 23650353

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Project description:ObjectiveNational and international medical organizations and boards have recognized the importance of Evidence Based Medicine (EBM) and emphasized that EBM training should be included in medical education programs. Although some Turkish medical schools have developed and implemented EBM training programs, no validated Turkish language assessment tool has been available to compare the effectiveness of these training programs to national or international standards. The aim of this study is to cross-culturally adapt the Fresno Test, which is a validated English language tool utilized worldwide in the assessment of EBM training.MethodsThis study is a cross-sectional validation study, which was performed in two stages: Cross-cultural adaptation of the Fresno Test into Turkish; and evaluation of the psychometric properties, validity, reliability and responsiveness, of the Turkish version of the Fresno Test.ResultsThe content validity of the test was evaluated by experienced physicians in the field of Evidence-Based Medicine, and the content validity index was 1.00. The Cronbach α coefficient was 0.78 on the post-test results. The intraclass correlation (ICC) coefficient and the kappa analysis were calculated to evaluate inter-rater reliability. The ICC coefficients ranged from 0.66 to 0.97 for pre- and post-test results. The Kappa coefficients were 1.00 for all pre-test and post-test questions except one post-test question which was 0.89. The change score of the Fresno Test was used to evaluate responsiveness. The students' score of the Turkish Fresno Test was 49.9 ±18.2 pre-training and 118.9 ±26.3 post-training with a change of 69 points (95% CI, 63.9-74.2). The Cohen's effect size was 3.04 (95% CI, 2.6-3.5) indicating a very large change in scores.ConclusionsThe Turkish adapted Fresno Test used to evaluate students' success and program effectiveness is a valid and reliable measurement tool. It will be of great benefit for the comparison of the effectiveness of Turkish education programs nationally and cross-culturally.

Dataset Information

Frequent adaptation and the McDonald-Kreitman test.

Publications

Frequent adaptation and the McDonald-Kreitman test.

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