RT Journal Article
SR Electronic
T1 A model of functionally buffered deleterious mutations can lead to signatures of positive selection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.14.480440
DO 10.1101/2022.02.14.480440
A1 Runxi Shen
A1 Miwa Wenzel
A1 Philipp W Messer
A1 Charles F. Aquadro
YR 2022
UL http://biorxiv.org/content/early/2022/06/29/2022.02.14.480440.abstract
AB Selective pressures on DNA sequences often result in signatures of 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 the experimentalists. Amino acid fixations driven by natural selection in protein coding genes are often associated with genetic conflict or changing biological purposes, leading to proteins with new functionality. Here, we propose that amino acid changes can also be correlated with a return to the original function after a period of relaxed selective constraint. Dynamic environments and changing population sizes offer opportunities for fluctuations in selective constraints on genes. We suggest that an evolutionary process in which a period of relaxed selective constraint can allow for slightly deleterious mutations to fix in a population by drift, and increased selective constraint can result in positive selection for residues that bring the gene back to its optimal functional state. We designed a model to investigate this possibility using the functionally critical bag of marbles (bam) gene in D. melanogaster.Bam, along with other germline genes, may experience variation in selective constraint due to the presence or absence of the endosymbiont bacteria Wolbachia, which infects many arthropod species episodically. We use simulations to implement this model and find that signatures of positive selection for the amino acid changes resembling the original states after the loss of Wolbachia can be detected by the MK test. However, the proportion of adaptive amino acids and the power of the test are both significantly lower than seen in parallel simulations of a change-in-function model that favors proteins with diversified amino acids to escape Wolbachia’s manipulation of reproduction.Competing Interest StatementThe authors have declared no competing interest.