Biology subjects

Ruzicka, F.

Publications and source records attributed to Ruzicka, F..

8 recordsLinked to original sources

bioRxiv2026

The evolution of context-specific dominance during selective sweeps

Dominance is a widespread feature of genetic variants which affects life-history traits and fitness. Although dominance is generally thought to be an intrinsic property of genetic variants, it can sometimes evolve, as in the classic case of melanism in the peppered moth. The broader question of how likely dominance is to evolve is, however, controversial, because conditions favouring dominance evolution are often restrictive. Here, we revisit Haldanes classic hypothesis that dominance might evolve during the spread of beneficial mutations to fixation (i.e., during selective sweeps). We first confirm results of earlier models that sweeps of unconditionally beneficial mutations generate little potential for dominance to evolve, even in cases where modifier alleles segregate prior to selective sweeps. However, when sweeping beneficial alleles trade off between different environments -- which we explore with the illustrative case of sexually antagonistic selection -- the scope for dominance evolution expands. This occurs because modifier alleles can alter dominance separately in each environment, increasing the mean fitness of heterozygotes, prolonging the sojourn time of the sweep, and generating more heterozygosity upon which the modifier can act. In extreme cases, beneficial mutations that were initially destined for fixation can undergo a "dominance reversal" as a result of dominance evolution, converting them to balanced polymorphisms. We quantify how regularly dominance reversals of sweeping sexually antagonistic alleles can be expected to evolve. Overall, our results highlight conditions that allow the dominance of beneficial mutations to evolve, which we discuss in light of data on the frequency of selective sweeps, standing genetic variation for modifiers, and plasticity of modifier effects.

evolutionary biology↗

bioRxiv2026

Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory

A widespread observation in molecular evolution is that X-linked genes evolve faster--and often adapt faster--than autosomal genes. Three main ideas have been put forward to explain "faster-X" adaptation. The first is that new beneficial mutations are typically partially recessive with respect to fitness, leading to more efficient selection in hemizygous males. The second is that sex differences in recombination, or sex differences in variance in reproductive success, enhance the effective population size on the X chromosome relative to autosomes. Both ideas have limitations: the first conflicts with theories of dominance, in which beneficial mutations are proposed to be partially dominant, while the second only applies to some taxa. Here we tested a third, newly-proposed theory, in which mutations with large "scaled phenotypic effects" (i.e., large effects relative to the distance to a phenotypic optimum) experience more positive selection on the X. Specifically, we used three proxies for scaled phenotypic effects--amino-acid dissimilarity, sequence conservation, and gene age--and estimated X and autosomal rates of adaptation of nonsynonymous mutations across effect-size classes. We did this in three lineages with a well-documented faster-X: Drosophila melanogaster, Mus musculus, and Homo sapiens. As expected, we found that large-effect mutations were more likely to be under purifying selection and less likely to be under positive selection than small-effect mutations. However, contrary to the new theory, faster-X adaptation was not enriched among large-effect mutations. Overall, our results highlight an unresolved gap between patterns of sex chromosome evolution and theories of dominance, and the need for more direct empirical data on the dominance of new beneficial mutations. Significance statementIn many species, genes on the X chromosome undergo more adaptation than autosomal genes, but it is not clear why this pattern of "faster-X" occurs. One possibility is that recessive beneficial mutations drive the effect, but theories of dominance propose instead that beneficial mutations should be dominant. Meanwhile, alternative explanations (e.g., sex differences in recombination or sex differences in variance in reproductive success) can only apply to some taxa. Here we tested a new idea, which proposes that the effect is driven by mutations with large effects. However, data from fruit flies, humans and mice did not provide support for the new theory. Our work highlights an unresolved gap between patterns of sex chromosome evolution and theories of dominance.

evolutionary biology↗

bioRxiv2025

A century of theories of balancing selection

Traits that affect organismal fitness are often very genetically variable. This genetic variation is vital for populations to adapt to their environments, but it is also surprising given that nature (after all) "selects" the best genotypes at the expense of those that fall short. Explaining the extensive genetic variation of fitness-related traits is thus a longstanding puzzle in evolutionary biology, with cascading implications for ecology, conservation, and human health. Balancing selection--an umbrella term for scenarios of natural selection that maintain genetic variation-- is a century-old explanation to resolve this paradox that has gained recent momentum from genome-scale methods for detecting it. Yet evaluating whether balancing selection can, in fact, resolve the paradox is challenging, given the logistical constraints of distinguishing balancing selection from alternative hypotheses and the daunting collection of theoretical models that formally underpin this debate. Here, we track the development of balancing selection theory over the last century and provide an accessible review of this rich collection of models. We first outline the range of biological scenarios that can generate balancing selection. We then examine how fundamental features of genetic systems--including non-random mating between individuals, differences in ploidy, genetic drift, and different genetic architectures of traits-- have been progressively incorporated into the theory. We end by linking these theoretical predictions to ongoing empirical efforts to understand the evolutionary processes that explain genetic variation.

evolutionary biology↗

bioRxiv2022

Improving fMRI in Parkinson's Disease by Accounting for Brain Region-Specific Activity Patterns

In functional magnetic imaging (fMRI) in Parkinsons disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structures temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loops structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n=31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

neuroscience↗

bioRxiv2021

Polygenic signals of sexually antagonistic selection in contemporary human genomes

Sex differences in the fitness effects of genetic variants can influence the rate of adaptation and the maintenance of genetic variation. For example, "sexually antagonistic" (SA) variants, which are beneficial for one sex and harmful for the other, can both constrain adaptation and increase genetic variability for fitness components such as survival, fertility, and disease susceptibility. However, detecting variants with sex-differential fitness effects is difficult, requiring genome sequences and fitness measurements from large numbers of individuals. Here, we develop new theory for studying sex-differential selection across a complete life cycle, and test our models with genotypic and reproductive success data from ~250,000 UK Biobank individuals. We uncover polygenic signals of sex-differential selection affecting survival, reproductive success and overall fitness, with signals of sex-differential reproductive selection reflecting a combination of SA polymorphisms and sexually concordant polymorphisms in which the strength of selection differs between the sexes. Moreover, these signals hold up to rigorous controls that minimise the contributions of potential confounders, including sequence mapping errors, population structure, and ascertainment bias. Functional analyses reveal that sex-differentiated sites are enriched in phenotype-altering genomic regions, including coding regions and loci affecting a range of quantitative traits. Population genetic analyses show that sex-differentiated sites exhibit evolutionary histories dominated by genetic drift and/or transient balancing selection, but not long-term balancing selection, which is consistent with theoretical predictions of effectively weak SA balancing selection in historically small populations. Overall, our results are consistent with polygenic sex-differential--including SA--selection in humans. Evidence for sex-differential selection is particularly strong for variants affecting reproductive success, in which the potential contributions of non-random sampling to statistical signals of sex-differentiation can be excluded.

evolutionary biology↗

bioRxiv2020

A non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster exhibits antagonistically pleiotropic fitness effects

The amount of genetic variation for fitness within populations tends to exceed that expected under mutation-selection-drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here we identify a non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster and measure survival and reproductive components of fitness in males and females of replicate lines carrying one or the other allele. Expressing the fruitless region in a hemizygous state we observe a pattern of AP, with one allele resulting in greater reproductive fitness while the other confers greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, suggesting widespread epistatic effects. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as fruitless, may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.

evolutionary biology↗

bioRxiv2020

The search for sexually antagonistic genes: Practical insights from studies of local adaptation and statistical genomics

Sexually antagonistic (SA) genetic variation--in which genotypes favoured in one sex are disfavoured in the other--is predicted to be common and has been documented in several animal and plant populations, yet we currently know little about its pervasiveness among species or its population genetic basis. Recent applications of genomics in studies of SA genetic variation have highlighted considerable methodological challenges to the identification and characterisation of SA genes, raising questions about the feasibility of genomic approaches for inferring SA selection. The related fields of local adaptation and statistical genomics have previously dealt with similar challenges, and lessons from these disciplines can therefore help overcome current difficulties in applying genomics to study SA genetic variation. Here, we integrate theoretical and analytical concepts from local adaptation and statistical genomics research--including FST and FIS statistics, genome-wide association studies (GWAS), pedigree analyses, reciprocal transplant studies, and evolve-and-resequence (E&R) experiments--to evaluate methods for identifying SA genes and genome-wide signals of SA genetic variation. We begin by developing theoretical models for between-sex FST and FIS, including explicit null distributions for each statistic, and using them to critically evaluate putative signals of sex-specific selection in previously published datasets. We then highlight new statistics that address some of the limitations of FST and FIS, along with applications of more direct approaches for characterising SA genetic variation, which incorporate explicit fitness measurements. We finish by presenting practical guidelines for the validation and evolutionary analysis of candidate SA genes and discussing promising empirical systems for future work. Impact SummaryGenome sequences carry a record of the evolutionary and demographic histories of natural populations. Research over the last two decades has dramatically improved our ability to detect genomic signals of adaptation by natural selection, including several widely-used methods for identifying genes underlying local adaptation and quantitative trait variation. Yet the application of these methods to identify sexually antagonistic (SA) genes--wherein variants that are adaptive for one sex are maladaptive for the other--remains under-explored, despite the potential importance of SA selection as a mechanism for maintaining genetic variation. Indeed, several lines of evidence suggest that SA genetic variation is common within animal and plant populations, underscoring the need for analytical methods that can reliably identify SA genes and genomic signals of SA genetic variation. Here, we integrate statistics and experimental designs that were originally developed within the fields of local adaptation and statistical genomics and apply them to the context of sex-specific adaptation and SA genetic variation. First, we evaluate and extend statistical methods for identifying signals of SA variation from genome sequence data alone. We then apply these methods to re-analyse previously published datasets on allele frequency differences between sexes--a putative signal of SA selection. Second, we highlight more direct approaches for identifying SA genetic variation, which utilise experimental evolution and statistical associations between individual genetic variants and fitness. Third, we provide guidelines for the biological validation, evolutionary analysis, and interpretation of candidate SA polymorphisms. By building upon the strong methodological foundations of local adaptation and statistical genomics research, we provide a roadmap for rigorous analyses of genetic data in the context of sex-specific adaptation, thereby facilitating insights into the role and pervasiveness of SA variation in adaptive evolution.

evolutionary biology↗

bioRxiv2017

Sexual antagonism exerts evolutionarily persistent genomic constraints on sexual differentiation in Drosophila melanogaster

The evolution of sexual dimorphism is constrained by a shared genome, leading to sexual antagonism where different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal D. melanogaster fly lines to perform a genome-wide association study of sexual antagonism. We identify ~230 chromosomal clusters of candidate antagonistic SNPs. In contradiction to classic theory, we find no clear evidence that the X chromosome is a hotspot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range, indicating widespread and evolutionarily persistent (>10,000 years) genomic constraints. Based on our results, we propose that antagonistic variation accumulates due to constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.

evolutionary biology↗