Determining the probability of hemiplasy in the presence of incomplete lineage sorting and introgression
Abstract
The incongruence of character states with phylogenetic relationships is often interpreted as evidence of convergent evolution. However, trait evolution along discordant gene trees can also generate these incongruences – a phenomenon known as hemiplasy. Classic comparative methods do not account for discordance, resulting in incorrect inferences about the number, timing, and direction of trait transitions. Biological sources of discordance include incomplete lineage sorting (ILS) and introgression, but only ILS has received theoretical consideration in the context of hemiplasy. Here, we present a model that shows introgression makes hemiplasy more likely, such that methods that account for ILS alone will be conservative. We also present a method and software (HeIST) for making statistical inferences about the probability of hemiplasy and homoplasy in large datasets that contain both ILS and introgression. We apply our methods to two empirical datasets, finding that hemiplasy is likely to contribute to the observed trait incongruences in both.
Data availability
Availability of the lizard genomic data and Heliconius phylogenetic network is detailed in the Acknowledgements section of the source manuscript. Source code and test cases for our software HeIST are freely available from the GitHub repository. Source data files have been provided for Figures 1, 4, 5, and 6. The Appendix details all the mutation rate parameters of our mathematical model.
-
Raw sequencing reads from ultraconserved elements of Australasian skinksNCBI Sequence Read Archive, BioProject PRJNA420910.
-
Data from: Genomic architecture and introgression shape a butterfly radiationDryad Digital Repository, doi:10.5061/dryad.b7bj832.
Article and author information
Author details
Funding
National Science Foundation (DEB-1936187)
- Matthew W Hahn
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antonis Rokas, Vanderbilt University, United States
Version history
- Received: October 6, 2020
- Accepted: December 18, 2020
- Accepted Manuscript published: December 21, 2020 (version 1)
- Version of Record published: January 11, 2021 (version 2)
- Version of Record updated: November 19, 2021 (version 3)
Copyright
© 2020, Hibbins et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,776
- Page views
-
- 166
- Downloads
-
- 12
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Evolutionary Biology
- Genetics and Genomics
In many species, meiotic recombination events tend to occur in narrow intervals of the genome, known as hotspots. In humans and mice, double strand break (DSB) hotspot locations are determined by the DNA-binding specificity of the zinc finger array of the PRDM9 protein, which is rapidly evolving at residues in contact with DNA. Previous models explained this rapid evolution in terms of the need to restore PRDM9 binding sites lost to gene conversion over time, under the assumption that more PRDM9 binding always leads to more DSBs. This assumption, however, does not align with current evidence. Recent experimental work indicates that PRDM9 binding on both homologs facilitates DSB repair, and that the absence of sufficient symmetric binding disrupts meiosis. We therefore consider an alternative hypothesis: that rapid PRDM9 evolution is driven by the need to restore symmetric binding because of its role in coupling DSB formation and efficient repair. To this end, we model the evolution of PRDM9 from first principles: from its binding dynamics to the population genetic processes that govern the evolution of the zinc finger array and its binding sites. We show that the loss of a small number of strong binding sites leads to the use of a greater number of weaker ones, resulting in a sharp reduction in symmetric binding and favoring new PRDM9 alleles that restore the use of a smaller set of strong binding sites. This decrease, in turn, drives rapid PRDM9 evolutionary turnover. Our results therefore suggest that the advantage of new PRDM9 alleles is in limiting the number of binding sites used effectively, rather than in increasing net PRDM9 binding. By extension, our model suggests that the evolutionary advantage of hotspots may have been to increase the efficiency of DSB repair and/or homolog pairing.
-
- Evolutionary Biology
- Microbiology and Infectious Disease
Drug resistance remains a major obstacle to malaria control and eradication efforts, necessitating the development of novel therapeutic strategies to treat this disease. Drug combinations based on collateral sensitivity, wherein resistance to one drug causes increased sensitivity to the partner drug, have been proposed as an evolutionary strategy to suppress the emergence of resistance in pathogen populations. In this study, we explore collateral sensitivity between compounds targeting the Plasmodium dihydroorotate dehydrogenase (DHODH). We profiled the cross-resistance and collateral sensitivity phenotypes of several DHODH mutant lines to a diverse panel of DHODH inhibitors. We focus on one compound, TCMDC-125334, which was active against all mutant lines tested, including the DHODH C276Y line, which arose in selections with the clinical candidate DSM265. In six selections with TCMDC-125334, the most common mechanism of resistance to this compound was copy number variation of the dhodh locus, although we did identify one mutation, DHODH I263S, which conferred resistance to TCMDC-125334 but not DSM265. We found that selection of the DHODH C276Y mutant with TCMDC-125334 yielded additional genetic changes in the dhodh locus. These double mutant parasites exhibited decreased sensitivity to TCMDC-125334 and were highly resistant to DSM265. Finally, we tested whether collateral sensitivity could be exploited to suppress the emergence of resistance in the context of combination treatment by exposing wildtype parasites to both DSM265 and TCMDC-125334 simultaneously. This selected for parasites with a DHODH V532A mutation which were cross-resistant to both compounds and were as fit as the wildtype parent in vitro. The emergence of these cross-resistant, evolutionarily fit parasites highlights the mutational flexibility of the DHODH enzyme.