Biology subjects

Tiedemann, R.

Publications and source records attributed to Tiedemann, R..

7 recordsLinked to original sources

bioRxiv2024

Mitochondrial genomes of three Melampus species (Ellobiidae; Gastropoda) and a proposed mitochondrial control region for Euthyneura

Melampus bidentatus was recently divided into three genetically divergent cryptic species: M. bidentatus, M. jaumei and M. gundlachi. We have assembled and annotated a mitochondrial genome for each of these species. Comparisons with other taxa showed that these three species possess a gene order that is distinct from the conserved gene order found in the six (out of nine available) Ellobiid genera. Among the species with a derived gene order, mean nucleotide divergence over all genes was on average 1.57x higher than among mitogenomes with the conserved gene order. This suggests varying evolutionary rates of mitochondrial genes in this family. We also use comparisons among 130 mitochondrial genomes within Euthyneura to support the presence of a control region preceding the Isoleucin-tRNA, including in the novel genomes presented here.

genomics↗

bioRxiv2024

UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation

The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. Nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). Here, we profile contributions of UHRF1 and DNMT1 to genome-wide DNA methylation inheritance and dissect specific roles for ubiquitin signaling in this process. We reveal DNA methylation maintenance at low-density CpGs is vulnerable to disruption of UHRF1 ubiquitin ligase activity and DNMT1 ubiquitin reading activity through UIM1. Hypomethylation of low-density CpGs in this manner induces formation of partially methylated domains (PMD), a methylation signature observed across human cancers. Furthermore, disrupting DNMT1 UIM2 function abolishes DNA methylation maintenance. Collectively, we show DNMT1-dependent DNA methylation inheritance is a ubiquitin-regulated process and suggest a disrupted UHRF1-DNMT1 ubiquitin signaling axis contributes to the development of PMDs in human cancers.

genomics↗

bioRxiv2023

Gene and allele specific expression underlying the electric signal divergence in African weakly electric fish

In the African weakly electric fish genus Campylomormyrus, electric organ discharge (EOD) signals are strikingly different in shape and duration among closely related species, contribute to pre-zygotic isolation and may have triggered an adaptive radiation. We performed mRNA sequencing on electric organs (EOs) and skeletal muscles (SMs; from which the EOs derive) from three species with short (0.4 ms), medium (5 ms), and long (40 ms) EODs and two different cross-species hybrids. We identified 1,444 up-regulated genes in EO shared by all five species/hybrids cohorts, rendering them candidate genes for EO-specific properties in Campylomormyrus. We further identified several candidate genes, including KCNJ2 and KLF5, their up-regulation may contribute to increased EOD duration. Hybrids between a short (C. compressirostris) and a long (C. rhynchophorus) discharging species exhibit EODs of intermediate duration and showed imbalanced expression of KCNJ2 alleles, pointing towards a cis-regulatory difference at this locus, relative to EOD duration. KLF5 is a transcription factor potentially balancing potassium channel gene expression, a crucial process for the formation of an EOD. Unraveling the genetic basis of the species-specific modulation of the EOD in Campylomormyrus is crucial for understanding the adaptive radiation of this emerging model taxon of ecological (perhaps even sympatric) speciation.

evolutionary biology↗

bioRxiv2023

Select EZH2 inhibitors enhance the viral mimicry effects of DNMT inhibition through a mechanism involving calcium-calcineurin-NFAT signaling

DNA methyltransferase (DNMT) inhibitors are FDA-approved for various hematological malignancies but have limited efficacy in solid tumors. DNA hypomethylation with these drugs is associated with elevated lysine 27 tri-methylation on histone H3 (H3K27me3). We hypothesized that this EZH2-dependent repressive mark limits the full potential of DNMT inhibition. Here, we show in cell line and tumoroid models of colorectal cancer, that low-dose DNMT inhibition sensitizes cells to selective EZH2 inhibitors that have limited single agent toxicity, and that EZH2 inhibition enhances DNMT inhibitor-driven molecular and therapeutic effects. Through integrative epigenomic analyses, we reveal that DNMT inhibition induces H3K27me3 accumulation at genomic regions poised with EZH2. Unexpectedly, combined treatment alters the epigenome landscape to promote transcriptional upregulation of the calcium-calcineurin-NFAT signaling pathway. Blocking this pathway limits the transcriptional activating effects of the drug combination, including expression of transposable elements and innate immune response genes within a viral defense pathway. Consistently, we demonstrate positive correlations between DNMT inhibitor- and innate immune response-associated transcription profiles and calcium signal activation in primary human colon cancer specimens. Collectively, our study demonstrates that compensatory EZH2 activity following DNA hypomethylation presents a barrier to the therapeutic action of DNMT inhibition in colon cancer, reveals a new application of EZH2 inhibitors beyond cancers associated with PRC2 hyperactivity, and links calcium-calcineurin-NFAT signaling to epigenetic therapy-induced viral mimicry. HighlightsO_LISelect EZH2 inhibitors enhance the transcriptional activating and antiproliferative effects of DNA hypomethylating agents in colon cancer cells. C_LIO_LIThe mechanism involves blockade of H3K27me3 accumulation in regions of the genome poised for PRC2 activity. C_LIO_LIDNMT inhibitor + EZH2 inhibitor treatment transcriptionally upregulates calcium-calcineurin- NFAT signaling, and this pathway is necessary for complete induction of viral mimicry and innate immune response pathways. C_LIO_LIThe therapeutic utility of EZH2 inhibitors may be extended beyond cancers with PRC2 hyperactivity in combination regimens with DNMT inhibitors. C_LI

cancer biology↗

bioRxiv2019

Introgression of Austrian fire-bellied toads (Bombina bombina) into northern German populations confirmed by complete mitochondrial genomes and transcriptome-wide Single Nucleotide Polymorphisms (SNPs)

The fire-bellied toad (Bombina bombina) is a small amphibian species inhabiting the lowlands of Central and Eastern Europe. Continual population fragmentation has caused a decrease in genetic diversity and gene flow in margin populations in Northern Germany. Previous research using mitochondrial control region data uncovered a translocation of allochthonous toads from Austria into a single northern German population, Hogsdorf. Microsatellite and MHC data also confirmed this introgression, but were limited in revealing the true extent of this translocation for all investigated populations. Here, we utilize complete mitochondrial genomes and nuclear data, in the form of transcriptomes, to unravel the full extent of admixture from this translocation. The increased number of loci enabled us to uncover signs of introgression in four out of the five northern populations investigated. Moreover, as hybrids between B. bombina and its sister species, B. variegata, have been reported in Austria, we also investigated whether B. variegata alleles were translocated into the northern gene pool. We found evidence for hybridization between Austrian B. bombina and B. variegata, as well as traces of B. variegata alleles in one of the five German populations included in this study. These findings present the first reported case of introgressed relict B. variegata alleles from the Southern lineage being detected in Northern Germany.

evolutionary biology↗

bioRxiv2018

High quality whole genome sequence of an abundant Holarctic odontocete, the harbour porpoise (Phocoena phocoena)

The harbour porpoise (Phocoena phocoena) is a highly mobile cetacean found in waters across the Northern hemisphere. It occurs in coastal water and inhabits water basins that vary broadly in salinity, temperature, and food availability. These diverse habitats could drive differentiation among populations. Here we report the first harbour porpoise genome, assembled de novo from a Swedish Kattegat individual. The genome is one of the most complete cetacean genomes currently available, with a total size of 2.7 Gb and 50% of the total length found in just 34 scaffolds. Using the largest 122 scaffolds, we were able to validate a high level of homology to the chromosome-level genome assembly of the closest related species for which such resource was available, the domestic cattle (Bos taurus). The draft annotation comprises 22,154 predicted gene models, which we further annotated through matches to the NCBI nucleotide database, GO categorization, and motif prediction. To infer the adaptive abilities of this species, as well as their population history, we performed a Bayesian skyline analysis, and produced results that are concordant with the demographic history of this species, including expansion and fragmentation events. Overall, this genome assembly, together with the draft annotation, represents a crucial addition to the limited genetic markers currently available for the study of porpoises and Phocoenidae conservation, phylogeny, and evolution.

genomics↗

bioRxiv2018

Spotlight on islands: on the origin and diversification of a new lineage of the Italian wall lizard Podarcis siculus in the western Pontine Islands

Groups of proximate continental islands may conceal more tangled phylogeographic patterns than oceanic archipelagos as a consequence of repeated sea level changes, which allow populations to experience gene flow during periods of low sea level stands and isolation by vicariant mechanisms during periods of high sea level stands. Here, we describe for the first time an ancient and diverging lineage of the Italian wall lizard Podarcis siculus from the western Pontine Islands. We used nuclear and mitochondrial DNA sequences of 156 individuals with the aim of unraveling their phylogenetic position, while microsatellite loci were used to compare several a priori insular biogeographic models of migration with empirical data. Our results suggest that the western Pontine populations colonized the islands early during their Pliocene volcanic formation, while populations from the eastern Pontine Islands seem to have been introduced recently. The inter-island genetic makeup indicates an important role of historical migration, probably due to glacial land bridges connecting islands followed by a recent vicariant mechanism of isolation. Moreover, the most supported migration model predicted higher gene flow among islands sharing a longitudinal arrangement. Considering the threatened status of small insular endemic populations, we suggest this new evolutionarily independent unit be given priority in conservation efforts.

evolutionary biology↗