Biology subjects

Crona, K.

Publications and source records attributed to Crona, K..

3 recordsLinked to original sources

bioRxiv2026

The lack of simplicity in sequence-fitness relationships

AO_SCPLOWBSTRACTC_SCPLOWGene interactions play an important role in the development of antimicrobial drug resistance and other evolutionary processes of medical importance. Empirical studies have revealed multiple peaks, inaccessible trajectories, and constraints on mutation order. Higher order epistasis is associated with obstacles in fitness landscapes. However, its significance has been debated in recent years, sometimes through reinterpretations of data from previous publications. We suggest that local higher order interactions may help reconcile these seemingly contradictory findings. Rank order based methods can be informative when other methods fail to detect consequential interactions. In addition to conventional rank order methods, including sign epistasis, we introduce signed bipyramids. A bipyramid interaction compares extreme genotypes against their intermediates, for example a triple mutant and the wild-type against the corresponding single mutants. In general, interactions are signed if they are implied by the rank order alone.

evolutionary biology↗

bioRxiv2025

Recombination peaks and fast evolution

AO_SCPLOWBSTRACTC_SCPLOWGenetic recombination can speed up or slow down evolution toward the global optimum. For analyzing mutational trajectories to the optimum it is conventional to study peaks in the fitness landscapes. However, such mutational peaks cannot provide a complete picture of the interplay between mutations, recombination and selection. Here we use recombination peaks as an additional tool. Informally, a recombination peak is a set of genotypes such that no allele shuffling among members can improve average fitness. If conventional peaks are optimal with respect to mutations, then recombination peaks are optimal with respect to recombination. The approach applies to general fitness landscapes with an arbitrary number of alleles and loci, and our experiments involve up to five alleles. One of the most frequently observed patterns of epistasis in nature is diminishing returns epistasis, i.e., the combined effect of beneficial mutations is smaller than a multiplicative expectation would predict. Recombination tends to speed up adaptation toward a peak whenever there is a systematic pattern of diminishing returns epistasis near the peak. The opposite is true for increasing returns epistasis. Mixed curvature is more challenging to analyze. Recombination peaks provide a language for describing effects of recombination, and threshold results are discussed accordingly. The experiments suggest that recombination is more likely to speed up adaptation for larger fitness landscapes.

evolutionary biology↗

bioRxiv2017

Inferring Genetic Interactions From Comparative Fitness Data

AO_SCPLOWBSTRACTC_SCPLOWDarwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax, the fungus Aspergillus niger, and the TEM-family of {beta}-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

evolutionary biology↗