Biology subjects

Draghi, J. A.

Publications and source records attributed to Draghi, J. A..

3 recordsLinked to original sources

bioRxiv2025

Epigenetic variation can promote adaptation by smoothing rugged fitness landscapes

Heritable non-genetic phenotypic variation--broadly, epigenetics--can potentially influence evolutionary outcomes as direct targets of selection or through interactions with genetic variation. While their evolutionary benefits in generating phenotypic diversity in changing environments is well-characterized, there has been relatively little consideration of how the joint influence of epigenetic changes and mutations would affect traversal of multi-peak adaptive landscapes. Here, we discover general principles for how epigenetics, by generating an epigenetic quasispecies (clusters of semi-stable phenotypes mapped to a single genotype), tends to improve adaptive outcomes of an asexual population on rugged fitness landscapes even without environmental change. In particular, rapid epigenetic changes can sometimes smooth out suboptimal fitness peaks through incorporating fitness contributions of epimutations, allowing access to better adaptive outcomes. Remarkably, the average impact of epigenetics is more strongly influenced by an approximate balance between switching rates rather than the absolute rate at which those switches occur. These findings demonstrate that epigenetic changes can be influential even without having strong heritability and have a striking, yet generally invisible, beneficial role in shaping a populations adaptive trajectory. Significance StatementSelection can act upon individuals with epigenetic differences, but it is unclear how much long-term effect this can have on evolutionary trajectories if the epigenetic changes only last a limited number of generations. When the environment changes or more than one functionality is needed simultaneously, it is apparent how bet hedging or division of labour can be advantageous, but what about in a single, constant environment? Here, we find that epigenetics, by allowing individuals rapid yet heritable access to multiple alternate phenotypes, can change the outcome of genetic evolution and has the tendency to remove local fitness peaks and allow adaptation to find higher optima. As such, epigenetics, despite being transient, can profoundly affect adaptive trajectories.

evolutionary biology↗

bioRxiv2024

Relaxed selection can speed the evolution of complex adaptations

Natural selection drives adaptive evolution and removes deleterious mutations; these effects are countervailing when a complex adaptation requires mutations that are initially deleterious when they arise, but beneficial in combination. While many models of this dynamic consider how genetic drift or other influences can aid valley crossing by weakening selection, we lack a general, analytical treatment of when relaxed selection might speed this type of adaptation. Here we use simulation and analysis to show that relaxed selection is generally favorable for valley-crossing when adaptive pathways require more than a single deleterious step. We also demonstrate that spatial heterogeneity in selection pressures could, by relaxing selection, allow populations to cross valleys much more rapidly than expected. These results relate to several applications of evolutionary theory to complex systems ranging from host-pathogen evolution to search algorithms in computer science.

evolutionary biology↗

bioRxiv2020

Epistatic interactions shape the interplay between beneficial alleles and gain or loss of pathways in the evolution of novel metabolism

Fitness landscapes are often invoked to interpret the effects of allele substitutions and their interactions; however, evolution also includes larger changes like gene loss and acquisition. Previous work with the methylotrophic bacterium Methylorubrum extorquens AM1 identified strongly beneficial mutations in a strain evolved to utilize a novel, Foreign pathway in place of its native central metabolic pathway for growth on methanol. These mutations were consistently beneficial, regardless of the order in which they arose. Here we extend this analysis to consider loss or acquisition of metabolic pathways by examining strains relying upon either the Native pathway, or both ( Dual) pathways present. Unlike in the Foreign pathway context in which they evolved, these alleles were often deleterious in these alternative genetic backgrounds, following patterns that were strongly contingent on the specific pathways and other evolved alleles present. Landscapes for these alternative pathway backgrounds altered which genotypes correspond to local fitness peaks and would restrict the set of accessible evolutionary trajectories. These epistatic interactions negatively impact the probability of maintaining multiple degenerate pathways, making it more difficult for these pathways to coevolve. Together, our results highlight the uncertainty of retaining novel functions acquired via horizontal gene transfer (HGT), and that the potential for cells to either adopt novel functions or to maintain degenerate pathways together in a genome is heavily dependent upon the underlying epistatic interactions between them. Author SummaryThe evolution of physiology in microbes has important impacts ranging from global cycling of elements to the emergence and spread of pathogens and their resistance to antibiotics. While genetic interactions between mutations in evolving lineages of microbes have been investigated, these have not included the acquisition of novel genes on elements like plasmids, and thus how these elements interact with existing alleles. The dynamics of novel gene retention are of interest from both positive (e.g., biotechnology) and negative (e.g., antimicrobial resistance) practical impacts. We find that the patterns of interactions between evolved alleles appear substantially different, and generally much less positive, when moved into novel genetic backgrounds. Additionally, these preexisting alleles were found to have strong impacts on the ability of genotypes to maintain - and in rare cases coevolve with - novel genes and pathways. These results show that even though they evolved separately, the particular alleles in a genetic background, and importantly the physiological impacts they confer, weigh heavily on whether genes for novel metabolic processes are maintained.

evolutionary biology↗