Biology subjects

Nickel, J.

Publications and source records attributed to Nickel, J..

4 recordsLinked to original sources

bioRxiv2026

β-Ketoacyl Synthase II Homologs from a Ladderane-Producing Organism Form a Ketosynthase/Chain Length Factor-like functional heterodimer

Ladderanes are extraordinary, highly strained chemical structures consisting of linearly concatenated cyclobutane rings. Ladderane-containing fatty acids are found in the lipids of anaerobic ammonium oxidizing (anammox) bacteria, reducing the proton permeability of their membranes to support their unique metabolism. Almost nothing is known about the biosynthesis of ladderanes, but a gene cluster unique to ladderane-producing bacteria is likely to be involved. This cluster encodes radical SAM enzymes as well as homologs of enzymes known from fatty acid biosynthesis. Amongst these are two homologs of FabF, the enzyme performing chain elongation in canonical fatty acid synthesis. The presence of two chain-elongating enzymes is unexpected; a single one would be expected to suffice, and the fact that one of the two homologs has a mutated, nonfunctional catalytic triad deepens the mystery. Here we present an in-depth characterization of the FabF homologs from anammox organisms, using biochemistry, enzymology, structural biology and computational biology. We show that the two homologs form a heterodimer analogous to the ketosynthase/chain length factor complexes known from polyketide synthases. This heterodimer is capable of performing the decarboxylation of malonate-loaded acyl carrier protein, thus initiating fatty acid biosynthesis. The crystal structure of the heterodimer explains how homodimer formation is avoided, and shows the details of the substrate binding tunnel. Mechanism-based crosslinking studies of wild-type and mutant heterodimers show the influence of residues on both subunits on substrate preference (which differs from canonical FabFs), and, together with computational studies, the crystal structure of the heterodimer in complex with substrate-loaded ACP helps explain its preference for ladderane-specific ACP. The results clearly refute an early proposal for a ladderane biosynthetic mechanism and greatly expand our current knowledge on how anammox bacteria produce their extraordinary lipids.

biochemistry↗

bioRxiv2025

Complex patterns of hitchhiking mutation load among stickleback populations

Positive selection causes beneficial alleles to rapidly rise to high frequency in a population. This can cause linked genetic variation to "hitchhike", and thereby also rise in frequency. This linked variation may include deleterious recessive alleles, previously neutrally harbored at low frequency in heterozygous genotypes. Modeling studies have shown that local effective population size and reduced recombination rate should contribute to the probability of deleterious mutations being swept to high frequency by being linked to beneficial alleles in selective sweeps or inversions. Marine sticklebacks have repeatedly adapted to thousands of freshwater habitats that became available after the last ice age, resulting in the formation of distinct marine and freshwater ecotypes. Selection acts on ancient standing genetic variation present in marine populations, causing freshwater-adaptive alleles to increase rapidly over tens of generations. These genomic regions play a key role in the repeated freshwater adaptation of morphological, physiological, and behavioral traits, and evolve under strong selection. Thus, threespine stickleback are an ideal system for investigating the impact of hitchhiking mutation load. We estimate the mutation load in regions of low recombination, including inversions, and the Eda haplotype. We find little evidence for the accumulation of deleterious alleles among genomic regions and populations. Inversions deviated from Hardy-Weinberg equilibrium in several populations, exhibiting an excess of homozygotes. These observations are consistent with purging facilitated by recombination in inversion karyotypes. We conclude that adaptation in threespine stickleback is not limited by hitchhiking deleterious mutations. Significance statementHitchhiking is a ubiquitous force in population genetics, shaping genetic diversity across the genome. Threespine stickleback are a model system for studying parallel adaptation to ecological variation, with low recombination genomic regions known to drive ecological adaptation. A key question is whether a deleterious mutation load is associated with adaptation in this system. We find that hitchhiking mutation load patterns are complex and do not conform to simple model predictions, despite some widespread patterns shared among populations. Our findings suggest that purging in homozygous karyotypes may be critical in reducing deleterious mutation load.

evolutionary biology↗

bioRxiv2020

Spontaneous rate of clonal mutations in Daphnia galeata

Mutations are the ultimate source of heritable variation and therefore the fuel for evolution, but direct estimates exist only for few species. We estimated the spontaneous nucleotide mutation rate among clonal generations in the waterflea Daphnia galeata with a short term mutation accumulation approach. Individuals from eighteen mutation accumulation lines over five generations were deep genome sequenced to count de novo mutations that were not present in a pool of F1 individuals, representing the parental genotype. We identified 12 new nucleotide mutations in 90 clonal generational passages. This resulted in an estimated haploid mutation rate of 0.745 x 10-9 (95% c.f. 0.39 x 10-9 - 1.26 x 10-9), which is slightly lower than recent estimates for other Daphnia species. We discuss the implications for the population genetics of Cladocerans.

evolutionary biology↗

bioRxiv2018

Reproduction associated gene expression under predation risk in Daphnia - a comparative transcriptomic approach

Phenotypic plastic responses allow organisms to rapidly adjust when facing environmental challenges - these responses comprise morphological, behavioral but also life-history changes. Alteration of life-history traits when exposed to predation risk have been reported often in the ecological and genomic model organism Daphnia. However, the molecular basis of this response is not well understood, especially in the context of fish predation. Here, we characterized the transcriptional profiles of two Daphnia galeata clonal lines with opposed life histories when exposed to fish kairomones. First, we conducted a differential gene expression, identifying a total of 125 candidate transcripts involved in the predator-induced response, uncovering substantial intra-specific variation. Second, we applied a gene co-expression network analysis to find clusters of tightly linked transcripts revealing the functional relations of transcripts underlying the predator-induced response. Our results showed that transcripts involved in remodeling of the cuticle, growth and digestion correlated with the response to environmental change in D. galeata. Furthermore, we used an orthology-based approach to gain functional information for transcripts lacking gene ontology (GO) information, as well as insights into the evolutionary conservation of transcripts. We could show that our candidate transcripts have orthologs in other Daphnia species but almost none in other arthropods. The unique combination of methods allowed us to identify candidate transcripts, their putative functions and evolutionary history associated with predator-induced responses in Daphnia. Our study opens up to the question as to whether the same molecular signature is associated fish kairomones-mediated life-history changes in other Daphnia species.

zoology↗