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A model of functionally buffered deleterious mutations can lead to signatures of positive selection

View ORCID ProfileRunxi Shen, View ORCID ProfileMiwa Wenzel, View ORCID ProfilePhilipp W Messer, View ORCID ProfileCharles F. Aquadro
doi: https://doi.org/10.1101/2022.02.14.480440
Runxi Shen
1Cornell University
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Miwa Wenzel
1Cornell University
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Philipp W Messer
1Cornell University
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Charles F. Aquadro
1Cornell University
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  • For correspondence: cfa1@cornell.edu
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Abstract

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. Here, we evaluate the expectations of a buffering mechanism driving selective amino acids to fixation, which is motivated by an observed phenotypic rescue of otherwise deleterious nonsynonymous substitutions at bag of marbles (bam) and Sex lethal (Sxl). These two important genes in Drosophila melanogaster were shown to experience strong episodic bursts of natural selection potentially due to infections of the endosymbiotic bacteria Wolbachia observed among multiple Drosophila species. Using simulations to implement and evaluate the evolutionary dynamics of a Wolbachia buffering model, we demonstrate that selectively fixed amino acid replacements will occur, but that proportion of adaptive amino acid fixations and the statistical power of the MK test to detect the departure from an equilibrium neutral model are both significantly lower than seen for an arms race/change-in-function model that favors proteins with diversified amino acids.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Additional simulations and analyses have been performed and the presentation of the story has been reframed and streamlined for ease of reading.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 31, 2023.
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A model of functionally buffered deleterious mutations can lead to signatures of positive selection
Runxi Shen, Miwa Wenzel, Philipp W Messer, Charles F. Aquadro
bioRxiv 2022.02.14.480440; doi: https://doi.org/10.1101/2022.02.14.480440
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A model of functionally buffered deleterious mutations can lead to signatures of positive selection
Runxi Shen, Miwa Wenzel, Philipp W Messer, Charles F. Aquadro
bioRxiv 2022.02.14.480440; doi: https://doi.org/10.1101/2022.02.14.480440

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