Brain region size generally scales allometrically with brain size, but mosaic shifts in brain region size independent of brain size have been found in several lineages and may be related to the evolution of behavioral novelty. African weakly electric fishes (Mormyroidea) evolved a mosaically enlarged cerebellum and hindbrain, yet the relationship to their behaviorally novel electrosensory system remains unclear. We addressed this by studying South American weakly electric fishes (Gymnotiformes) and weakly electric catfishes (Synodontis spp.), which evolved varying aspects of electrosensory systems, independent of mormyroids. If the mormyroid mosaic increases are related to evolving an electrosensory system, we should find similar mosaic shifts in gymnotiforms and Synodontis. Using micro-computed tomography scans, we quantified brain region scaling for multiple electrogenic, electroreceptive, and non-electrosensing species. We found mosaic increases in cerebellum in all three electrogenic lineages relative to non-electric lineages and mosaic increases in torus semicircularis and hindbrain associated with the evolution of electrogenesis and electroreceptor type. These results show that evolving novel electrosensory systems is repeatedly and independently associated with changes in the sizes of individual major brain regions independent of brain size, suggesting that selection can impact structural brain composition to favor specific regions involved in novel behaviors.
Brain measurement data is located in Supplementary File 1. Brain mass data is located in Supplementary File 2. All analysis code and phylogenetic trees are available in Dryad. The raw micro-computed tomography scans are too large to post (multiple TBs), but are available upon request. To request raw otophysan and/or osteoglossiform scans, contact the corresponding author. We ask that those who want access to the scan data send us an external hard drive, which we will upload all the data to and then return.
Data from: Convergent mosaic brain evolution is associated with the evolution of novel electrosensory systems in teleost fishesDryad Digital Repository, doi:10.5061/dryad.7d7wm37w5.
Data from: Brain mass and body mass datasets and phylogenies linked to brain-body allometry and the encephalization of birds and mammals.Figshare, doi:10.6084/m9.figshare.6803276.v1.
Data from: Exceptionally Steep Brain-Body Evolutionary Allometry Underlies the Unique Encephalization of OsteoglossiformesBrain Behav Evol, Supplementary Material, doi:10.1159/000519067.
Data from: Extreme Enlargement of the Cerebellum in a Clade of Teleost Fishes that Evolved a Novel Active Sensory SystemCurr Biol, doi:10.1016/j.cub.2018.10.038.
- Bruce A Carlson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: The methods in this study are consistent with euthanasia guidelines by the American Veterinary Medical Association and have been approved by the Animal Care and Use Committee at Washington University in St. Louis (Protocol ID 19-0974).
- Catherine Emily Carr, University of Maryland, United States
- Received: September 23, 2021
- Accepted: June 16, 2022
- Accepted Manuscript published: June 17, 2022 (version 1)
© 2022, Schumacher & Carlson
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.
Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene duplication ultimately acquire new interaction specificities to establish insulated paralogous signaling pathways. Here, we used ancestral sequence reconstruction to resurrect and characterize a bacterial two-component signaling system that duplicated in α-proteobacteria. We determined the interaction specificities of the signaling proteins that existed before and immediately after this duplication event and then identified key mutations responsible for establishing specificity in the two systems. Just three mutations, in only two of the four interacting proteins, were sufficient to establish specificity of the extant systems. Some of these mutations weakened interactions between paralogous systems to limit crosstalk. However, others strengthened interactions within a system, indicating that the ancestral interaction, although functional, had the potential to be strengthened. Our work suggests that protein-protein interactions with such latent potential may be highly amenable to duplication and divergence.
With the continual evolution of new strains of SARS-CoV-2 that are more virulent, transmissible, and able to evade current vaccines, there is an urgent need for effective anti-viral drugs SARS-CoV-2 main protease (Mpro) is a leading target for drug design due to its conserved and indispensable role in the viral life cycle. Drugs targeting Mpro appear promising but will elicit selection pressure for resistance. To understand resistance potential in Mpro, we performed a comprehensive mutational scan of the protease that analyzed the function of all possible single amino acid changes. We developed three separate high-throughput assays of Mpro function in yeast, based on either the ability of Mpro variants to cleave at a defined cut-site or on the toxicity of their expression to yeast. We used deep sequencing to quantify the functional effects of each variant in each screen. The protein fitness landscapes from all three screens were strongly correlated, indicating that they captured the biophysical properties critical to Mpro function. The fitness landscapes revealed a non-active site location on the surface that is extremely sensitive to mutation making it a favorable location to target with inhibitors. In addition, we found a network of critical amino acids that physically bridge the two active sites of the Mpro dimer. The clinical variants of Mpro were predominantly functional in our screens, indicating that Mpro is under strong selection pressure in the human population. Our results provide predictions of mutations that will be readily accessible to Mpro evolution and that are likely to contribute to drug resistance. This complete mutational guide of Mpro can be used in the design of inhibitors with reduced potential of evolving viral resistance.