Bacterial adaptation to antibiotic combinations depends on the joint inhibitory effects of the two drugs (drug interaction, DI) and how resistance to one drug impacts resistance to the other (collateral effects, CE). Here we model these evolutionary dynamics on two-dimensional phenotype spaces that leverage scaling relations between the drug-response surfaces of drug sensitive (ancestral) and drug resistant (mutant) populations. We show that evolved resistance to the component drugs-and in turn, the adaptation of growth rate-is governed by a Price equation whose covariance terms encode geometric features of both the two-drug response surface (DI) in ancestral cells and the correlations between resistance levels to those drugs (CE). Within this framework, mean evolutionary trajectories reduce to a type of weighted gradient dynamics, with the drug interaction dictating the shape of the underlying landscape and the collateral effects constraining the motion on those landscapes. We also demonstrate how constraints on available mutational pathways can be incorporated into the framework, adding a third key driver of evolution. Our results clarify the complex relationship between drug interactions and collateral effects in multi-drug environments and illustrate how specific dosage combinations can shift the weighting of these two effects, leading to different and temporally-explicit selective outcomes.
Data used in this paper was taken from a public repository:Dean, Ziah; Maltas, Jeff; Wood, Kevin (2020), Antibiotic interactions shape short-term evolution of resistance in Enterococcus faecalis, Dryad, Dataset, https://doi.org/10.5061/dryad.j3tx95x92There are no restrictions on any new results.
Data from: Antibiotic interactions shape short-term evolution of resistance in Enterococcus faecalisDryad Digital Repository, doi:10.5061/dryad.j3tx95x92.
- Kevin B Wood
- Kevin B Wood
- Erida Gjini
- Erida Gjini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- C. Brandon Ogbunugafor, Yale University, United States
© 2021, Gjini & Wood
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.
The study of color patterns in the animal integument is a fundamental question in biology, with many lepidopteran species being exemplary models in this endeavor due to their relative simplicity and elegance. While significant advances have been made in unraveling the cellular and molecular basis of lepidopteran pigmentary coloration, the morphogenesis of wing scale nanostructures involved in structural color production is not well understood. Contemporary research on this topic largely focuses on a few nymphalid model taxa (e.g., Bicyclus, Heliconius), despite an overwhelming diversity in the hierarchical nanostructural organization of lepidopteran wing scales. Here, we present a time-resolved, comparative developmental study of hierarchical scale nanostructures in Parides eurimedes and five other papilionid species. Our results uphold the putative conserved role of F-actin bundles in acting as spacers between developing ridges, as previously documented in several nymphalid species. Interestingly, while ridges are developing in P. eurimedes, plasma membrane manifests irregular mesh-like crossribs characteristic of Papilionidae, which delineate the accretion of cuticle into rows of planar disks in between ridges. Once the ridges have grown, disintegrating F-actin bundles appear to reorganize into a network that supports the invagination of plasma membrane underlying the disks, subsequently forming an extruded honeycomb lattice. Our results uncover a previously undocumented role for F-actin in the morphogenesis of complex wing scale nanostructures, likely specific to Papilionidae.
5-Methylcytosine (5mC) and DNA methyltransferases (DNMTs) are broadly conserved in eukaryotes but are also frequently lost during evolution. The mammalian SNF2 family ATPase HELLS and its plant ortholog DDM1 are critical for maintaining 5mC. Mutations in HELLS, its activator CDCA7, and the de novo DNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. We here examine the coevolution of CDCA7, HELLS and DNMTs. While DNMT3, the maintenance DNA methyltransferase DNMT1, HELLS, and CDCA7 are all highly conserved in vertebrates and green plants, they are frequently co-lost in other evolutionary clades. The presence-absence patterns of these genes are not random; almost all CDCA7 harboring eukaryote species also have HELLS and DNMT1 (or another maintenance methyltransferase, DNMT5). Coevolution of presence-absence patterns (CoPAP) analysis in Ecdysozoa further indicates coevolutionary linkages among CDCA7, HELLS, DNMT1 and its activator UHRF1. We hypothesize that CDCA7 becomes dispensable in species that lost HELLS or DNA methylation, and/or the loss of CDCA7 triggers the replacement of DNA methylation by other chromatin regulation mechanisms. Our study suggests that a unique specialized role of CDCA7 in HELLS-dependent DNA methylation maintenance is broadly inherited from the last eukaryotic common ancestor.