Biology subjects

Ivankovic, M.

Publications and source records attributed to Ivankovic, M..

5 recordsLinked to original sources

bioRxiv2023

A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence

The planarian Schmidtea mediterranea can regenerate its entire body from small tissue fragments and is studied as regeneration model species. The assembly and functional analysis of planarian genomes has proven challenging due its high A/T content (70% A/T), repetitive nature, and limited transferability of routine laboratory protocols due to their divergent biochemistry. Only few and often fragmented genome assemblies are currently available, and open challenges include the provision of well-annotated chromosome-scale reference assemblies of the model species and other planarians for a comparative genome evolution perspective. Here we report a haplotype-phased, chromosome-scale genome assembly and high-quality gene annotations of the sexual S2 strain of S. mediterranea and provide putative regulatory region annotations via optimized ATAC-seq and ChIP-seq protocols. To additionally leverage sequence conservation for regulatory element annotations, we generated chromosome-scale genome assemblies and chromatin accessibility data for the three closest relatives of S. mediterranea: S. polychroa, S. nova, and S. lugubris. We find substantial divergence in protein-coding sequences and regulatory regions, yet reveal remarkable conservation in ChIP-mark bearing open chromatin regions identified as promoters and enhancers in S. mediterranea. The resulting high-confidence set of evolutionary conserved enhancers and promoters provides a valuable resource for the analysis of gene regulatory circuits and their evolution within the taxon. In addition, our four chromosome-scale genome assemblies provide a first comparative perspective on planarian genome evolution. Our analyses reveal frequent retrotransposon-associated chromosomal inversions and inter-chromosomal translocations that lead to a degradation of synteny across the genus. Interestingly, we further find independent and near-complete losses of the ancestral metazoan synteny across Schmidtea and two other flatworm groups, indicating that platyhelminth genomes largely evolve without syntenic constraints. Our work provides valuable genome resources for the planarian research community and sets a foundation for the comparative genomics of planarians. We reveal a contrast between the fast structural evolution of planarian genomes and the conservation of their regulatory elements, suggesting a unique genome evolution in flatworms where gene positioning may not be essential.

genomics↗

bioRxiv2022

Probing the evolutionary dynamics of whole-body regeneration within planarian flatworms

Why some animals can regenerate while many others cannot remains a fascinating question. Even amongst planarian flatworms, well-known for their ability to regenerate complete animals from small body fragments, species exist that have restricted regeneration abilities or are entirely regeneration incompetent. Towards the goal of probing the evolutionary dynamics of regeneration, we have assembled a diverse live collection of planarian species from around the world. The combined quantification of species-specific head regeneration abilities and comprehensive transcriptome-based phylogeny reconstructions reveals multiple independent transitions between robust whole-body regeneration and restricted regeneration in the freshwater species. Our demonstration that the RNAi-mediated inhibition of canonical Wnt signalling can nevertheless bypass all experimentally tractable head regeneration defects in the current collection indicates that the pathway may represent a hot spot in the evolution of planarian regeneration defects. Combined with our finding that Wnt signalling has multiple roles in the reproductive system of the model species S. mediterranea, this raises the possibility of a trade-off between egg-laying and asexual reproduction by fission/regeneration as a driver of regenerative trait evolution. Although initial quantitative comparisons of Wnt signalling levels, reproductive investment, and regenerative abilities across the collection confirm some of the models predictions, they also highlight the diversification of molecular mechanisms amongst the divergent planarian lineages. Overall, our study establishes a framework for the mechanistic evolution of regenerative abilities and planarians as model taxon for comparative regeneration research.

evolutionary biology↗

bioRxiv2022

Top-down structuring of freshwater bacterial communities by mixotrophic and heterotrophic protists

Mixotrophic and heterotrophic protists hold a key position in aquatic microbial food webs. They account for the bulk of bacterivory in pelagic systems. However, the potential structuring effect of heterotrophic and especially mixotrophic protists on bacterial communities is far from clear. We conducted standardized short-term grazing experiments, to test for the overall impact on bacterial community structure and possible prey preferences of protist taxa with different phagotrophic nutritional modes. The used protist taxa covered a range from more phototrophic towards heterotrophic strategies, with obligate mixotrophic taxa employing phototrophy as the dominant strategy, towards facultative mixotrophic taxa relying more on phagotrophy, with the end of this gradient being covered by a phagoheterotroph lacking phototrophic capacity. Bacterioplankton from different lake systems was enriched and used to represent semi-natural bacterial assemblages that served as prey communities. Our study showed that similarities in protistan nutritional modes were reflected in similarities in their overall impact on bacterial communities. The impact intensity increased towards clear phagotrophic strategies, with mixotrophs in the phototrophic end of the gradient rather having a stabilizing impact on bacterial communities. Obligate mixotrophs grazed diverse prey in small amounts, while towards strict heterotrophic nutrition we observed an ingestion increase and selective depletion of bacteria with potential high growth rates. Future global change scenarios supporting the domination of obligate mixotrophic bacterivores might promote higher bacterial diversity in the illuminated zone of lakes.

ecology↗

bioRxiv2022

Content-aware image restoration improves spatiotemporal resolution in luminescence microscopy.

Luminescence microscopy is a powerful tool in biomedical imaging applications due to its intrinsically high signal to noise ratio. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content-aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique.

cell biology↗

bioRxiv2021

Discovery of an unusual high number of de novo mutations in sperm of older men using duplex sequencing

De novo mutations (DNMs) are an important player in heritable diseases and evolution. Of particular interest are highly recurrent DNMs associated with congenital disorders that have been described as selfish mutations expanding in the male germline, thus becoming more frequent with age. Here, we have adapted duplex sequencing (DS), an ultra-deep sequencing method that renders sequence information on both DNA strands; thus, one mutation can be reliably called in millions of sequenced bases. With DS, we examined [~]4.5 kb of the FGFR3 coding region in sperm DNA from older and younger donors. We identified sites with variant frequencies of 10-4 to 10-5, with an overall mutation frequency of the region of [~]6x10-7. Some of the substitutions were re-current and were found at a higher variant frequency in older donors than in younger ones, or exclusively, in older donors. Also, older donors harbored more mutations associated with congenital disorders. Other mutations were present in both age groups suggesting that these might result from a different mechanism (e.g., post-zygotic mosaicism). We also observed that independent of age, the frequency and deleteriousness of the mutational spectra was more similar to COSMIC than to gnomAD variants. Our approach is an important strategy to identify mutations that could be associated with a gain-of-function of the receptor tyrosine kinase activity, with unexplored consequences in a society with delayed fatherhood.

genetics↗