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Martens, J.

Publications and source records attributed to Martens, J..

11 recordsLinked to original sources
bioRxiv2026

An introgressed haplotype decouples phenotype from genome-wide ancestry

Introgression redistributes genetic variation among diverging lineages, shaping evolution-ary trajectories and contributing to phenotypic evolution. Yet how localized introgressed genomic regions persist despite extensive genomic homogenization remains poorly under-stood. Here, we investigate the evolutionary history of the northeastern Iranian great tit (Parus major intermedius), a grey-plumaged member of the great tit complex occurring at the eastern range margin of the green- and yellow-plumaged major lineage, adjacent to the grey-plumaged Central Asian bokharensis lineage, and long regarded as a putative hybrid. We find that P. m. intermedius retains predominantly major-derived genomic ancestry despite its grey plumage, revealing extensive genomic homogenization across the genome. Surprisingly, a single localized introgressed haplotype on chromosome 24 retains bokharensis-derived ancestry, exhibits elevated genomic differentiation relative to the genomic background, and overlaps the carotenoid-processing gene BCO2, a strong candidate underly-ing plumage pigmentation. Our findings provide a genomic explanation for the discordance between phenotype and genome-wide ancestry, demonstrating how localized introgression can preserve genomic regions associated with phenotypic divergence despite extensive genomic homogenization. This system illustrates how individual genomic regions can retain distinct evolutionary histories long after the surrounding genome has largely homogenized.

evolutionary biology↗
bioRxiv2026

Circulating immune signatures reveal targetable inflammatory pathways in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is one of the most lethal malignancies. Immune dysregulation is believed to play an important role in ATC. Here, we aimed to characterize the systemic inflammation and the function of circulating immune cells of patients with ATC. First, we retrospectively assessed biochemical parameters of patients with ATC and observed that high systemic inflammation correlated with worse survival. Next, we prospectively investigated the inflammatory proteome, single-cell peripheral blood mononuclear cell transcriptome and epigenetic changes. Circulating concentrations of proinflammatory cytokines were increased in ATC patients. This proinflammatory profile was apparent at the level of gene transcription and chromatin accessibility, especially in monocytes. These findings were substantiated by an increased capacity of peripheral blood mononuclear cells of ATC patients to produce IL-6, IL-8 and lactate. As IL-6 is known to promote tumor cell survival, we assessed its capacity to influence ATC cell proliferation. Blocking IL-6/gp130/Jak/STAT3 pathway inhibited proliferation of ATC cell lines in vitro. In conclusion, these findings show that ATC is characterized by inappropriate systemic inflammation and epigenetic and transcriptional reprogramming of circulating monocytes. Proinflammatory cytokines released by monocytes support survival and proliferation of ATC tumor cells, suggesting a therapeutic potential of targeting this pathway in ATC patients.

cancer biology↗
bioRxiv2026

Cultural transmission and genomic co-divergence in the willow tit across the Palearctic

Cultural transmission of mating behaviour can both promote and constrain genetic divergence, yet its long-term population-genetic consequences remain unclear. In songbirds, learned song can generate behavioural isolation, but its potential to shape genome-wide differentiation at continental scales is rarely assessed. Willow tits provide a compelling system, as three culturally transmitted song types are largely allopatric across the Palearctic, while northern populations exhibit mixed repertoires. Here, we combined a chromosome-level reference genome, whole-genome resequencing of 88 willow tits (Poecile montanus) spanning all 14 subspecies, and palaeodistribution modelling to reconstruct the species evolutionary history across the Palearctic. Phylogenetic and demographic analyses indicate an origin in Asia during the Late Pliocene to Early Pleistocene, followed by expansions that yielded three deeply diverged genomic lineages in the Asian, Central European, and Northern Palearctic regions. The boundaries of these lineages coincide with major song-type divisions. Tests of historical allele sharing show that gene flow occurred preferentially among lineages that share the same or similar song types, even after accounting for geography, consistent with learned song contributing to prezygotic isolation. Peripheral, song-monotypic populations exhibit signatures of repeated bottlenecks associated with glacial isolation, whereas large northern populations retained broader song repertoires and signals of long-term connectivity. These results provide genome-wide continental evidence that culturally transmitted song mirrors and likely reinforces genomic structure through time in a widespread passerine bird.

evolutionary biology↗
bioRxiv2026

Does the mid-domain effect shape interaction networks along environmental gradients?

The mid-domain effect (MDE) predicts that geometric constraints drive unimodal species richness patterns within bounded gradients. However, the role of this effect in ecological networks is currently unexplored. Here we evaluate the role of the MDE in structuring interaction networks. We combine null-model simulations and empirical analyses of plant-pollinator and ant-plant networks along elevational gradients to assess whether the MDE can drive systematic variation in network structure. Our simulations demonstrated that the MDE alone can generate unimodal/U-shaped patterns in network metrics such as connectance, generality, and vulnerability. However, empirical networks only partially conformed to MDE predictions, with deviations indicating the likely influence of other ecological processes. MDE-based models best explained patterns in network-level specialization and nestedness, while only partially explaining patterns in connectance and generality. Because MDEs can shape interaction networks, MDE null models should be used when quantifying the influence of other ecological processes on network structure.

ecology↗
bioRxiv2024

Community context influences the conjugation efficiency of E. coli

In urinary tract infections different bacteria can live in a polymicrobial community, it is unknown how such community members affect the conjugation rate of uropathogenic Escherichia coli. We investigated the influence of the polymicrobial urinary tract infection (UTI) community context on the conjugation rate of E. coli isolates in artificial urine medium. Pairwise conjugation rate experiments were conducted between a donor E. coli strain containing pOXA-48 and six uropathogenic E. coli isolates in the presence and absence of five community members to elucidate their effect on the rate of conjugation. We found that the basal conjugation rates in the absence of community members are genotype dependent. Interestingly, bacterial interactions have an overall positive effect on E. coli conjugation rates. Particularly Gram-positive enterococcal species were found to enhance the conjugation rates of most uropathogenic E. coli isolates. We hypothesize that the nature and co-culture of the interactions is important for these increased conjugation rates in AUM.

ecology↗
bioRxiv2022

Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia

The heterogeneity and evolution of AML blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole-exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. The single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells. In summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.

cancer biology↗
bioRxiv2020

Pan-cancer landscape of homologous recombination deficiency

Homologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we developed a genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n=3,504) and primary (n=1,854) pan-cancer cohort revealed HRD was most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. Biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 was the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. While the specific genetic cause of HRD was cancer type specific, biallelic inactivation was predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).

cancer biology↗
bioRxiv2019

5-Fluorouracil treatment induces characteristic T>G mutations in human cancer

5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. It is proposed that 5-FU possesses anticancer properties via the interference with nucleotide synthesis and incorporation into DNA. As both mechanisms may have a mutational impact on both surviving tumor and healthy cells, we treated intestinal organoids with 5-FU followed by whole genome sequencing analysis and uncovered a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context. Analysis of tumor whole genome sequencing data confirmed that this signature can also be identified in vivo in colorectal and breast cancer patients that have undergone treatment with 5-FU. We also found that more 5-FU mutations are induced in TP53 null backgrounds which may be of clinical relevance. Taken together, our results demonstrate that 5-FU is mutagenic and may drive tumor evolution and increase the risk of secondary malignancies. Furthermore, the identified signature shows a strong resemblance to COSMIC signature 17, the hallmark signature of treatment-naive esophageal and gastric tumors, which indicates that distinct endogenous and exogenous triggers can converge onto highly similar mutational signatures.

cancer biology↗
bioRxiv2018

Polyomavirus T-Antigen Induces APOBEC3B Expression using a LXCXE-Dependent and TP53-Independent Mechanism

APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomaviruses and papillomaviruses use dominant oncoproteins to induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of APOBEC3B upregulation by the polyomavirus large T-antigen. First, truncated T-antigen (truncT) is sufficient for APOBEC3B upregulation and the RB interacting motif (LXCXE), but not the TP53 inhibition domain, is required. Second, upregulated APOBEC3B is strongly nuclear and partially localized to virus replication centers. Third, genetic knockdown of RB1 alone or in combination with RBL1 and/or RBL2 is insufficient to suppress truncT-mediated induction of APOBEC3B. Fourth, CDK4/6 inhibition by palbociclib is also insufficient to suppress truncT-mediated induction of APOBEC3B. Fifth, global gene expression analyses in a wide range of human cancers show significant associations between expression of APOBEC3B and other genes known to be regulated by the RB/E2F axis. These experiments combine to implicate the RB/E2F axis in promoting APOBEC3B transcription, yet they also suggest that the polyomavirus RB binding motif has in addition to RB inactivation at least one additional function for triggering APOBEC3B upregulation in virus-infected cells.\n\nIMPORTANCEThe APOBEC3B DNA cytosine deaminase is overexpresssed in many different cancers and correlated with elevated frequencies of C-to-T and C-to-G mutations in 5-TC motifs, oncogene activation, acquired drug resistance, and poor clinical outcomes. The mechanisms responsible for APOBEC3B overexpression are not fully understood. Here, we show that the polyomavirus truncated T-antigen (truncT) triggers APOBEC3B overexpression through its RB-interacting motif, LXCXE, which in turn likely enables one or more E2F family transcription factors to promote APOBEC3B expression. This work strengthens the mechanistic linkage between active cell cycling, APOBEC3B overexpression, and cancer mutagenesis. Although this mechanism damages cellular genomes, viruses may leverage it to promote evolution, immune escape, and pathogenesis. The cellular portion of the mechanism may also be relevant to non-viral cancers, where genetic mechanisms often activate the RB/E2F axis and APOBEC3B mutagenesis contributes to tumor evolution.

microbiology↗
bioRxiv2018

DNA methylation oscillation defines classes of enhancers

Understanding the regulatory landscape of human cells requires the integration of genomic and epigenomic maps, capturing combinatorial levels of cell type-specific and invariant activity states.\n\nHere, we segmented whole-genome bisulfite sequencing-derived methylomes into consecutive blocks of co-methylation (COMETs) to obtain spatial variation patterns of DNA methylation (DNAm oscillations) integrated with histone modifications and promoter-enhancer interactions derived from promoter capture Hi-C (PCHi-C) sequencing of the same purified blood cells.\n\nMapping DNAm oscillations onto regulatory genome annotation revealed that enhancers are enriched for DNAm hyper-oscillations (>30-fold), where multiple machine learning models support DNAm as predictive of enhancer location. Based on this analysis, we report overall predictive power of 99% for DNAm oscillations, 77.3% for DNaseI, 41% for CGIs, 20% for UMRs and 0% for LMRs, demonstrating the power of DNAm oscillations over other methods for enhancer prediction. Methylomes of activated and non-activated CD4+ T cells indicate that DNAm oscillations exist in both states irrespective of activation; hence they can be used to determine the location of latent enhancers.\n\nOur approach advances the identification of tissue-specific regulatory elements and outperforms previous approaches defining enhancer classes based on DNA methylation.

genomics↗