The McDonald and Kreitman test (MKT) is one of the most powerful and widely used methods to detect and quantify recurrent natural selection using DNA sequence data. Here we present iMKT (acronym for integrative McDonald and Kreitman test), a novel web-based service performing four distinct MKT types. It allows the detection and estimation of four different selection regimes -adaptive, neutral, strongly deleterious and weakly deleterious- acting on any genomic sequence. iMKT can analyze both user's own population genomic data and pre-loaded Drosophila melanogaster and human sequences of protein-coding genes obtained from the largest population genomic datasets to date. Advanced options in the website allow testing complex hypotheses such as the application example showed here: do genes located in high recombination regions undergo higher rates of adaptation? We aim that iMKT will become a reference site tool for the study of evolutionary adaptation in massive population genomics datasets, especially in Drosophila and humans. iMKT is a free resource online at https://imkt.uab.cat.
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http://dx.doi.org/10.1093/nar/gkz372 | DOI Listing |
G3 (Bethesda)
April 2024
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85719, USA.
Inferring the effects of positive selection on genomes remains a critical step in characterizing the ultimate and proximate causes of adaptation across species, and quantifying positive selection remains a challenge due to the confounding effects of many other evolutionary processes. Robust and efficient approaches for adaptation inference could help characterize the rate and strength of adaptation in nonmodel species for which demographic history, mutational processes, and recombination patterns are not currently well-described. Here, we introduce an efficient and user-friendly extension of the McDonald-Kreitman test (ABC-MK) for quantifying long-term protein adaptation in specific lineages of interest.
View Article and Find Full Text PDFBiol Rev Camb Philos Soc
February 2024
Senckenberg Biodiversity and Climate Research Institute (SBiK-F), Georg-Voigt-Strasse 14-16, Frankfurt am Main, 60325, Germany.
Half a century after its foundation, the neutral theory of molecular evolution continues to attract controversy. The debate has been hampered by the coexistence of different interpretations of the core proposition of the neutral theory, the 'neutral mutation-random drift' hypothesis. In this review, we trace the origins of these ambiguities and suggest potential solutions.
View Article and Find Full Text PDFEvolution
October 2023
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States.
Selective pressures on DNA sequences often result in departures from neutral evolution that can be captured by the McDonald-Kreitman (MK) test. However, the nature of such selective forces often remains unknown to experimentalists. Amino acid fixations driven by natural selection in protein-coding genes are commonly associated with a genetic arms race or changing biological purposes, leading to proteins with new functionality.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2023
Université de Lyon, Université Lyon 1, CNRS, VetAgro Sup, Laboratoire de Biométrie et Biologie Evolutive, UMR5558, 69100 Villeurbanne, France.
Adaptation in protein-coding sequences can be detected from multiple sequence alignments across species or alternatively by leveraging polymorphism data within a population. Across species, quantification of the adaptive rate relies on phylogenetic codon models, classically formulated in terms of the ratio of nonsynonymous over synonymous substitution rates. Evidence of an accelerated nonsynonymous substitution rate is considered a signature of pervasive adaptation.
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