ArticlePLoS biology2019
Genotype network intersections promote evolutionary innovation.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- The adaptive landscapes of three globaleLife · 2026Article
- Inference of fitness landscapes with heterogeneous patterns of epistasis across sites.bioRxiv : the preprint server for biology · 2026Article
- A simple model captures key characteristics of biological non-deterministic genotype-phenotype maps.PLoS computational biology · 2026Article
- Hierarchical genotype networks and incipient ecological speciation in Q[Formula: see text] phage quasispecies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional bottlenecks can emerge from non-epistatic underlying traits.PLoS computational biology · 2026Article
- Inference and Visualization of Complex Genotype-Phenotype Maps.Molecular biology and evolution · 2026Article
- Inference and visualization of complex genotype-phenotype maps withbioRxiv : the preprint server for biology · 2025Article
- Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole to triphosphate activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Genotype sampling for deep-learning assisted experimental mapping of a combinatorially complete fitness landscape.Bioinformatics (Oxford, England) · 2024Article
- An extension of the Walsh-Hadamard transform to calculate and model epistasis in genetic landscapes of arbitrary shape and complexity.PLoS computational biology · 2024Article
- Engineering is evolution: a perspective on design processes to engineer biology.Nature communications · 2024Article
- Frustration can Limit the Adaptation of Promiscuous Enzymes Through Gene Duplication and Specialisation.Journal of molecular evolution · 2024Article
- Open-endedness in synthetic biology: A route to continual innovation for biological design.Science advances · 2024Review
- Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein.Nature communications · 2023Article
- Robustness and innovation in synthetic genotype networks.Nature communications · 2023Article
- Article
- Experimental exploration of a ribozyme neutral network using evolutionary algorithm and deep learning.Nature communications · 2022Article
- A Family of Fitness Landscapes Modeled through Gene Regulatory Networks.Entropy (Basel, Switzerland) · 2022Article
- Dynamic RNA Fitness Landscapes of a Group I Ribozyme during Changes to the Experimental Environment.Molecular biology and evolution · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms of innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks-the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. However, the experimental characterization of genotype networks has been hindered by the vast number of genetic variants that need to be functionally analyzed. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions, and we use these data as a proxy for a genotype to fitness map where two functions come in close proximity. We find extensive functional overlap, and numerous genotypes can catalyze both functions. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. However, the rate of adaptation of the new function depends upon the local ruggedness around the starting location in the genotype network. As a consequence, one direction of adaptation is more rapid than the other. We find that periods of neutral evolution increase rates of adaptation to the new function by allowing populations to spread out in their genotype network. Our study reveals the properties of a fitness landscape where genotype networks intersect and the consequences for evolutionary innovations. Our results suggest that historic innovations in natural systems may have been facilitated by overlapping genotype networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.