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Epistasis, Pleiotropy, Robustness, and Evolvability: Insights into Evolutionary Dynamics
Dalarna University, School of Information and Engineering, Microdata Analysis. Dalarna University, School of Information and Engineering, Computing.ORCID iD: 0000-0001-9523-6689
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

The study of evolutionary dynamics requires a comprehensive understanding of how genetic interactions shape adaptation, particularly through the interplay of epistasis, pleiotropy, robustness, and evolvability. Despite significant advances in evolutionary modeling, existing frameworks often oversimplify genetic architectures, assuming fixed interactions and static environments. However, epistasis and pleiotropy are not static properties; they evolve over time, continuously reshaping the adaptive landscape. This dissertation addresses these limitations by developing a computational framework that extends the classic NK fitness landscape model through indirect encoding. This key innovation decouples epistasis and pleiotropy from landscape ruggedness, allowing these fundamental properties to evolve and to be studied independently. To systematically quantify genetic interactions, this research uses an Interaction Matrix (IM) as a tool, which captures the strength and distribution of genetic dependencies. This enables a structured approach to measuring epistasis (the degree of gene-gene interaction) and pleiotropy (the extent to which a single gene influences multiple traits). Furthermore, the study integrates Gene Regulatory Networks (GRNs) to explore how these interactions change over evolutionary time, providing insights into the role of genetic sparsity in shaping adaptive potential. The key question in evolutionary biology is how epistasis and pleiotropy influence the balance between robustness and evolvability. While robustness–the ability to maintain function despite mutations–ensures stability, evolvability–the capacity to generate beneficial variation–is crucial for long-term adaptation. The interplay between these properties is complex and widely debated. To explore this interplay, I focus on the Survival of the Flattest (SoF) phenomenon, where populations in high-mutation environments favor flatter fitness peaks over higher narrower peaks. This raises fundamental questions: How can populations remain on higher fitness peaks for extended periods? What mechanisms enable successful transitions between peaks, avoiding the SoF trap? In what scenarios does evolvability provide an advantage, and when is robustness more beneficial? I use the SoF model as a framework to investigate the role of epistasis and pleiotropy in this context. This dissertation provides new insights into these evolutionary challenges, offering a refined perspective on how populations navigate rugged landscapes, escape local fitness traps, and dynamically balance stability with adaptability. To further investigate these evolutionary dynamics, a dynamic fitness landscape is developed, allowing the study of how populations respond to changing environments. Unlike static models, the experimenter sets the velocity at which the landscape changes independently from other parameters, such as the ruggedness or the mutation rate. By varying key parameters such as ruggedness (K) and environmental change rate (V), the study examines their effects on genotype-phenotype (GP) mapping. To further validate the findings, real-world datasets were incorporated, bridging the gap between theoretical models and empirical data. The findings have broad implications beyond evolutionary biology, offering valuable insights for genetic engineering, synthetic biology, and evolutionary computation, where understanding and harnessing genetic interactions can drive innovations in biotechnology and artificial life systems. By providing a refined approach to studying how genetic architectures evolve and persist over time, this work lays a foundation for future research into the fundamental principles governing adaptive complexity. All complex systems are composed of interacting components, inherently shaped by epistasis and pleiotropy. While our model is not a literal replication of any single system, it captures these fundamental properties, allowing us to probe general principles that can illuminate the behavior of complex, real-world evolutionary dynamics. 

Place, publisher, year, edition, pages
Borlänge: Dalarna University, 2025.
Series
Dalarna Doctoral Dissertations ; 45
Keywords [en]
epistasis, pleiotropy, ruggedness, evolvability, NK fitness landscape, gene regulatory networks, interaction matrix, mutational robustness, survival of the flattest, genotype-phenotype mapping, dynamic fitness landscapes
National Category
Evolutionary Biology
Identifiers
URN: urn:nbn:se:du-50615ISBN: 978-91-88679-96-3 (print)OAI: oai:DiVA.org:du-50615DiVA, id: diva2:1959071
Public defence
2025-08-29, room B301, campus Borlänge and online, 13:00 (English)
Opponent
Supervisors
Available from: 2025-06-16 Created: 2025-05-19 Last updated: 2025-10-09Bibliographically approved
List of papers
1. An extension to the NK fitness landscape model to study pleiotropy, epistasis, and ruggedness independently
Open this publication in new window or tab >>An extension to the NK fitness landscape model to study pleiotropy, epistasis, and ruggedness independently
2022 (English)In: Proceedings of the 2022 IEEE Symposium Series on Computational Intelligence, SSCI 2022, Institute of Electrical and Electronics Engineers Inc. , 2022, p. 1259-1267Conference paper, Published paper (Refereed)
Abstract [en]

The NK model is designed to study evolutionary adaptation in rugged fitness landscapes. The factor K determines the number of interacting genes, their degree of pleiotropy and epistasis, and consequently the ruggedness of the fitness landscape. However, in natural organisms, the degree of epistatic interactions and the number of functions a gene can have are to a certain degree determining the ruggedness of the landscape. Still, pleiotropy and epistasis can evolve independently from each other, and are to some degree independent of the ruggedness of the landscape. Here, we propose an extension to the standard NK model to investigate these factors independently of each other. Over the course of evolution the computational model organisms can now change how their genes interact and how they control phenotypic traits. Further, the degree of epistasis and pleiotropy is affected by the ruggedness of the landscape and becomes reduced with increasing ruggedness. While this proves that the extension of the model performs as expected, the adaptations are minor, presumably because only relatively short periods of adaptations with few mutations can be studied. © 2022 IEEE.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers Inc., 2022
Keywords
Bioinformatics, Epistasi, Evolution, Evolutionary adaptation, Fitness land-scape, Fitness landscape, Interacting genes, Landscape model, NK-models, Pleiotropy, Ruggedness, Genes, epistasis
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-45563 (URN)10.1109/SSCI51031.2022.10022166 (DOI)000971973800168 ()2-s2.0-85147794543 (Scopus ID)9781665487689 (ISBN)
Conference
2022 IEEE Symposium Series on Computational Intelligence, SSCI 2022, Singapore, 4-7 December 2022
Available from: 2023-03-03 Created: 2023-03-03 Last updated: 2025-10-09Bibliographically approved
2. Evolution of Pleiotropy and Epistasis in a Gene Regulatory Network
Open this publication in new window or tab >>Evolution of Pleiotropy and Epistasis in a Gene Regulatory Network
2023 (English)In: ALIFE 2023. Ghost in The Machine. Proceedings of the Artificial Life Conference 2023, MIT Press, 2023Conference paper, Published paper (Refereed)
Abstract [en]

The study of gene regulatory networks (GRNs) is fundamental to the understanding of evolutionary dynamics and artificial life modeling. This paper presents an integration of a GRN into the NK-fitness landscape model and explores the impact of sparsity on epistasis and pleiotropy. As sparsity augments, gene interactions diminish, expectedly leading to a reduction in both epistasis and pleiotropy. Our findings corroborate the model’s response to such perturbations, demonstrating its potential for investigating a range of GRN adaptations within the NK-fitness landscape framework.

Place, publisher, year, edition, pages
MIT Press, 2023
Keywords
epistasis, pleiotropy, gene regulatory network, evolution
National Category
Computer and Information Sciences Evolutionary Biology
Identifiers
urn:nbn:se:du-47522 (URN)10.1162/isal_a_00604 (DOI)
Conference
2023 Artificial Life Conference, July 24–28 2023, online
Available from: 2023-12-18 Created: 2023-12-18 Last updated: 2025-10-09Bibliographically approved
3. Reducing Epistasis and Pleiotropy Can Avoid the Survival of the Flattest Tragedy
Open this publication in new window or tab >>Reducing Epistasis and Pleiotropy Can Avoid the Survival of the Flattest Tragedy
2024 (English)In: Biology, E-ISSN 2079-7737, Vol. 13, no 3, article id 193Article in journal (Refereed) Published
Abstract [en]

This study investigates whether reducing epistasis and pleiotropy enhances mutational robustness in evolutionary adaptation, utilizing an indirect encoded model within the “survival of the flattest” (SoF) fitness landscape. By simulating genetic variations and their phenotypic consequences, we explore organisms’ adaptive mechanisms to maintain positions on higher, narrower evolutionary peaks amidst environmental and genetic pressures. Our results reveal that organisms can indeed sustain their advantageous positions by minimizing the complexity of genetic interactions—specifically, by reducing the levels of epistasis and pleiotropy. This finding suggests a counterintuitive strategy for evolutionary stability: simpler genetic architectures, characterized by fewer gene interactions and multifunctional genes, confer a survival advantage by enhancing mutational robustness. This study contributes to our understanding of the genetic underpinnings of adaptability and robustness, challenging traditional views that equate complexity with fitness in dynamic environments. © 2024 by the authors.

Place, publisher, year, edition, pages
MDPI, 2024
Keywords
epistasis, mutational robustness, pleiotropy, survival of the flattest
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-48311 (URN)10.3390/biology13030193 (DOI)001191567600001 ()38534462 (PubMedID)2-s2.0-85188680430 (Scopus ID)
Available from: 2024-04-02 Created: 2024-04-02 Last updated: 2025-10-09
4. The Role of Pleiotropy and Epistasis on Evolvability and Robustness in a Two-Peak Fitness Landscape
Open this publication in new window or tab >>The Role of Pleiotropy and Epistasis on Evolvability and Robustness in a Two-Peak Fitness Landscape
2024 (English)In: Biology, E-ISSN 2079-7737, Vol. 13, no 12, article id 1003Article in journal (Refereed) Published
Abstract [en]

Understanding the balance between robustness and evolvability is crucial in evolutionary dynamics. This study aims to determine how varying mutation rates and valley depths affect this interplay during adaptation. Using a two-peak fitness landscape model requiring populations to cross a fitness valley to reach a higher peak, we investigate how mutation rates and valley depths influence both evolvability—the capacity to generate beneficial mutations—and mutational robustness, which stabilizes populations at the highest peak. Our experiments reveal that at low mutation rates, populations struggle to cross fitness valleys, reducing the occurrence of pioneers. As mutation rates increase, valley crossing becomes more frequent, but organisms forming a majority at the highest peak are less common and tend to arise at intermediate mutation rates. Although pioneers reach the highest peak, they are often replaced by more mutationally robust organisms that later form a majority. This suggests that while evolvability aids in valley crossing, long-term stability at the highest peak requires greater mutational robustness. Our findings highlight that adaptations in epistasis and pleiotropy facilitate the trade-off between evolvability and robustness, providing insights into how organisms navigate complex fitness landscapes. These results can also inform the design of genetic algorithms that balance evolvability with robustness to optimize outcomes. © 2024 by the authors.

Keywords
epistasis; evolvability; pleiotropy; robustness; survival of the flattest
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-49953 (URN)10.3390/biology13121003 (DOI)39765670 (PubMedID)2-s2.0-85213267560 (Scopus ID)
Available from: 2025-01-08 Created: 2025-01-08 Last updated: 2025-10-09
5. From Valleys to Peaks: The Role of Evolvability in Fitness Landscape Navigation
Open this publication in new window or tab >>From Valleys to Peaks: The Role of Evolvability in Fitness Landscape Navigation
2025 (English)In: PNAS Nexus, E-ISSN 2752-6542, Vol. 4, no 8, article id pgaf221Article in journal (Refereed) Published
Abstract [en]

Understanding the balance between evolvability and mutational robustness is crucial for exploring adaptation in complexfitness landscapes. This study examines how heterogeneous populations adapt under varying mutation rates (μ) andfitness landscape ruggedness (K), emphasizing their distinct starting conditions in valleys, slopes (low prominence), orpeaks (high prominence). Using an extended NK model, we simulate populations capable of initiating anywhere in thelandscape. Our findings reveal that starting positions strongly influence whether robustness or evolvability is advantageous.Populations beginning in low-prominence regions (valleys and slopes) exhibited high levels of epistasis (ϵ) and pleiotropy(π), enhancing evolvability and enabling exploration of the fitness landscape. In contrast, populations starting in highprominenceregions (peaks) reduced ϵ and π, prioritizing robustness to maintain stability against mutations. This studyhighlights the role of starting conditions in shaping evolutionary trajectories, offering insights into the interplay betweenevolvability and robustness.

Keywords
epistasis, pleiotropy, fitness landscape, evolvability, robustness
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-50616 (URN)10.1093/pnasnexus/pgaf221 (DOI)001541599100001 ()40757234 (PubMedID)2-s2.0-105012378249 (Scopus ID)
Available from: 2025-05-19 Created: 2025-05-19 Last updated: 2025-10-15Bibliographically approved
6. Continuous Evolution in the NK Treadmill Model
Open this publication in new window or tab >>Continuous Evolution in the NK Treadmill Model
2025 (English)In: Artificial Life, ISSN 1064-5462, E-ISSN 1530-9185, Vol. 31, no 3, p. 256-275Article in journal (Refereed) Published
Abstract [en]

The NK fitness landscape is a well-known model with which to study evolutionary dynamics in landscapes of different ruggedness. However, the model is static, and genomes are typically small, allowing observations over only a short adaptive period. Here we introduce an extension to the model that allows the experimenter to set the velocity at which the landscape changes independently from other parameters, such as the ruggedness or the mutation rate. We find that, similar to the previously observed complexity catastrophe, where evolution comes to a halt when environments become too complex due to overly high degrees of epistasis, here the same phenomenon occurs when changes happen too rapidly. Our expanded model also preserves essential properties of the static NK landscape, allowing for proper comparisons between static and dynamic landscapes.

Keywords
Fitness landscape, dynamic landscape, epistasis, pleiotropy, ruggedness, velocity
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-50247 (URN)10.1162/artl_a_00467 (DOI)001566839600001 ()39964771 (PubMedID)2-s2.0-105015685600 (Scopus ID)
Available from: 2025-02-26 Created: 2025-02-26 Last updated: 2025-10-31Bibliographically approved
7. How the necessity to be robust or evolvable shapes the genotype-phenotype map
Open this publication in new window or tab >>How the necessity to be robust or evolvable shapes the genotype-phenotype map
2025 (English)In: Nature Communications, E-ISSN 2041-1723Article in journal (Refereed) Submitted
Abstract [en]

The genotype-phenotype map determines how genetic variation translates into traits, influencing evolutionary adaptability. While previous models often assume a static relationship, genetic architectures evolve dynamically in response to selective pressures. In this study, we investigate how epistasis and pleiotropy adapt under varying fitness landscape ruggedness (K) and environmental variability (V ) together, shaping genetic robustness and evolvability. Using the NK treadmill model, we systematically explore the independent effects of K and V on genetic complexity. Our findings reveal that increased ruggedness (K) reduces genetic interdependencies, favoring modular architectures that enhance mutational robustness. Conversely, higher environmental variability (V ) promotes interconnected genetic networks, increasing evolvability. Empirical validation using bacterial genomes supports these results, showing strong correlations between genetic complexity measures and mutational robustness, reinforcing the role of environmental pressures in shaping genetic architectures.

Keywords
robustness, evolvability, genotype-phenotype map, epistasis, pleiotropy, changing fitness landscape, ruggedness, velocity
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:du-50617 (URN)
Available from: 2025-05-19 Created: 2025-05-19 Last updated: 2025-10-09Bibliographically approved

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Mehra, Priyanka

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