Biology subjects

Nowak, S.

Publications and source records attributed to Nowak, S..

9 recordsLinked to original sources

bioRxiv2026

Wolf microevolution in the melting pot: range expansion, population sympatry, dynamic mosaic admixture zone and asymmetric gene flow

Here we describe substantial range shifts of historically differentiated wolf populations and formation of novel sympatric zones during the recent decade in Central Europe. This region provides a natural laboratory for testing alternative scenarios of population interactions from continued isolation or restricted gene flow to progressive population fusion, while prompting a reassessment of their geographic ranges. Based on sampling across the Czech Republic and Slovakia obtained from large-scale monitoring programmes over five wolf years (2020/21_2024/25), complemented by comparative material from neighbouring regions, we analysed mitochondrial haplotypes, autosomal microsatellite genotypes and sex-linked loci. The Central European population with Baltic ancestry predominated across large parts of Central Europe including the Bohemian Massif with enclaves in the Western Carpathians. The Carpathian population was predominant in Slovakia, with a smaller satellite occurrence in the northern part of the Bohemian Massif. Alpine population was centred in the Alps but extended into southern parts of Bohemian Massif and Central German Uplands. Following the sporadic occurrence of admixed individuals, broad mosaic and dynamic sympatric zones have formed in the Czech Republic and Slovakia in the last decade. These scenarios could be facilitated by the presence of intermediate habitats and isolation of the Bohemian Massif structural basin, framed by a massive ring fault system. Recent-immigration estimates are asymmetric, with the largest mean contributions from the Alpine to the Central European population and from the Central European to the Carpathian population, with the second case potentially linked to source-sink dynamics driven by the hunting pressure within the Carpathian population (whereas the others are protected year-round). Whether increasing admixture will enhance viability of populations (that currently have small effective sizes) through genetic rescue or carry risks of outbreeding depression remains uncertain, highlighting the need for continued transboundary monitoring within conservation biology framework.

genetics↗

bioRxiv2026

Environmental drivers of heritable trait variation and lag of adaptation to climate in Hordeum murinum

1. Most plant species are genetically differentiated among populations, often reflected by phenotypic trait variation that corresponds to local adaptation. Yet the strength of local adaptation and heritable contribution to phenotypic traits vary across traits, species, and environments. Additionally, climate change is rapidly altering environmental conditions, and the climate may shift faster than populations can adapt or track the change via dispersal, resulting in adaptive lags. However, it remains unclear how widespread such adaptive lags are across plant species. 2. We focused on Hordeum murinum, an annual ruderal grass widespread in Europe. We combined continental-scale in situ measurements of 2070 plants across 207 populations with common garden experiments across two contrasting climates and two soil types to disentangle heritable variation from phenotypic plasticity and assess potential adaptive lags under climate change. 3. We found that heritable variation was pronounced in developmental traits, particularly flowering time and plant height, while seed weight, reproductive investment and SLA showed intermediate heritable contribution, and flag leaf area and total biomass were primarily plastic. Heritable trait variation was strongly associated with temperature at the populations origin, and trait clines were consistent with in situ patterns, suggesting that temperature is the main driver of genetic differentiation in H. murinum. However, we detected that fitness peaked in populations originating from warmer climates, indicating that evolutionary responses may not keep pace with rapid environmental shifts. 4. Synthesis: Our results highlight that H. murinum harbors substantial heritable variation, shaped primarily by temperature. However, the pace of evolutionary change may be insufficient to track ongoing climate change, leaving populations potentially vulnerable to future environmental conditions.

ecology↗

bioRxiv2026

Climate-driven in-situ trait variation in an annual ruderal grass across Europe

O_LIPlant functional traits link environmental conditions to plant performance and adaptation. Growing evidence shows that in-situ intraspecific trait variation can be as important as differences between species, yet large intraspecific datasets measured in situ are rare. While most studies focused on plant morphological traits, contents of elemental nutrients in the seeds received much less attention so far. C_LIO_LIWe conducted a large-scale in-situ study of the widespread ruderal grass Hordeum murinum. We sampled 2070 individuals from 207 populations from a large part of the native range in Europe and Northern Africa. In-situ, we measured seed ripening phenology and morphological traits, and analyzed the content of elemental nutrients in the seeds. C_LIO_LIWe found that Hordeum murinum grew larger, produced seeds later, and had heavier seeds in colder and wetter areas. Plants in denser vegetation were taller with heavier seeds but formed fewer spikes. Seed nutrient content generally declined with seed weight and was mainly driven by climate. Soil conditions had only minor effects on plant traits and seed nutrients. Population identity explained much of the variation, indicating a possible genetic component. C_LIO_LISynthesis: Our findings provide a comprehensive view of Hordeum murinum responding to environmental gradients across its European distribution. Climatic variables, especially temperature, are key drivers for reproductive success and seed nutrient content, while local environments, such as biotic pressures, are more critical for growth-related traits. These patterns indicate that H. murinum modulates its growth and reproductive investment along environmental gradients, balancing phenology, stress tolerance, and limited competitive capacity. C_LI

ecology↗

bioRxiv2022

Genomes of the extinct Sicilian wolf reveal a complex history of isolation and admixture with ancient dogs

The Sicilian wolf represented the only population of wolves living on a Mediterranean island until the first half of the twentieth century (1930s-1960s) 1-7. Previous studies hypothesised that they remained isolated from mainland wolves from the end of the Last Glacial Maximum (LGM) 8,9, until human persecutions led them to extinction 1-7. There are only seven known Sicilian wolf specimens from the 19th and 20th century preserved in museums in Italy and recent morphometric analyses assigned them to the new subspecies Canis lupus cristaldii 10. To better understand the origins of the Sicilian wolf, and its relationship to other wolf populations, we sequenced four whole genomes (3.8x-11.6x) and five mitogenomes. We investigated the relationship between Sicilian wolves and other modern breeds to identify potential admixture. Furthermore, considering that the last land-bridge between Sicily and Italy disappeared after the LGM 11, around 17 kya, we explored the possibility that the Sicilian wolf retained ancestry from ancient wolf and dog lineages. Additionally, we explored whether the long-term isolation might have affected the genomic diversity, inbreeding levels and genetic load of the Sicilian wolf. Our findings show that the Sicilian wolves shared most ancestry with the modern Italian wolf population but are better modelled as admixed with European dog breeds, and shared traces of Eneolithic and Bronze age European dogs. We also find signatures of severe inbreeding and low genomic diversity at population and individual levels due to long-term isolation and drift, suggesting also low effective population size.

genomics↗

bioRxiv2020

Estimating the effect-size of gene dosage on cognitive ability across the coding genome

Genomic Copy Number Variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect-size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect-sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs >50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect-size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of IQ when duplicated or deleted, respectively. Effect-sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect-sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect-size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect-sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways.

genetics↗

bioRxiv2020

Cell-free synthesis of natural compounds from genomic DNA of biosynthetic gene clusters

A variety of chemicals can be produced in a living host cell via optimized and engineered biosynthetic pathways. Despite the successes, pathway engineering remains demanding and partly impossible owing to the lack of specific functions or substrates in the host cell, its sensitivity in vital physiological processes to the heterologous components, or constrained mass transfer across the membrane. In this study, we demonstrate that cell-free systems can be useful in driving the characterization and engineering of biosynthetic pathways. We show that complex multidomain proteins involved in natural compound biosynthesis can be produced from encoding DNA in vitro in a minimal complex PURE system to directly run multistep reactions. We prove the concept of this approach on the direct synthesis of indigoidine and rhabdopeptides with the in vitro produced multidomain megasynthases BpsA and KJ12ABC. The in vitro produced proteins are analyzed in detail, i.e., in yield, quality, post-translational modification and specific activity, and compared to recombinantly produced proteins. Our study highlights cell-free PURE systems as suitable setting for the rapid engineering of biosynthetic pathways.

bioengineering↗

bioRxiv2020

Effects-sizes of deletions and duplications on autism risk across the genome

ObjectiveDeleterious copy number variants (CNVs) are identified in up to 20% of individuals with autism. However, only 13 genomic loci have been formally associated with autism because the majority of CNVs are too rare to perform individual association studies. To investigate the implication of undocumented CNVs in neurodevelopmental disorders, we recently developed a new framework to estimate their effect-size on intelligence quotient (IQ) and sought to extend this approach to autism susceptibility and multiple cognitive domains. MethodsWe identified CNVs in two autism samples (Simons Simplex Collection and MSSNG) and two unselected populations (IMAGEN and Saguenay Youth Study). Statistical models integrating scores of genes encompassed in CNVs were used to explain their effect on autism susceptibility and multiple cognitive domains. ResultsAmong 9 scores of genes, the "probability-of-being loss-of-function intolerant" (pLI) best explains the effect of CNVs on IQ and autism risk. Deletions decrease IQ by a mean of 2.6 points per point of pLI. The effect of duplications on IQ is three-fold smaller. The odd ratios for autism increases when deleting or duplicating any point of pLI. This increased autism risk is similar in subgroups of individuals below or above median IQ. Once CNV effects on IQ are accounted for, autism susceptibility remains mostly unchanged for duplications but decreases for deletions. Model estimates for autism risk overlap with previously published observations. Deletions and duplications differentially affect social communication, behaviour, and phonological memory, whereas both equally affect motor skills. ConclusionsAutism risk conferred by duplications is less influenced by IQ compared to deletions. CNVs increase autism risk similarly in individuals with high and low IQ. Our model, trained on CNVs encompassing >4,500 genes, suggests highly polygenic properties of gene dosage with respect to autism risk. These models will help interpreting CNVs identified in the clinic.

genetics↗

bioRxiv2018

Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains

Many important natural products are produced by non-ribosomal peptide synthetases (NRPSs) 1.These giant enzyme machines activate amino acids in an assembly line fashion in which a set of catalytically active domains is responsible for the section, activation, covalent binding and connection of a specific amino acid to the growing peptide chain 1,2. Since NRPS are not restricted to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would give access to a diverse range of peptides available biotechnologically. Here we describe a new fusion point inside condensation (C) domains of NRPSs that enables the efficient production of peptides, even containing non-natural amino acids, in yields higher than 280 mg/L. The technology called eXchange Unit 2.0 (XU2.0) also allows the generation of targeted peptide libraries and therefore might be suitable for the future identification of bioactive peptide derivatives for pharmaceutical and other applications.

synthetic biology↗

bioRxiv2017

Superposition of survival curves as a tool for epistasis analysis of longevity interventions

A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard epistasis analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate superposition principles that predict the survival curve resulting from a combination of two interventions based on the survival curves of the individual treatments, and quantify epistasis as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of 4 different longevity interventions in Caenorhabditis elegans. We find that epistasis is generally weak even when the standard analysis indicates otherwise.

genetics↗