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Scientific Reports Apr 2024The mammalian epidermis has evolved to protect the body in a dry environment. Genes of the epidermal differentiation complex (EDC), such as FLG (filaggrin), are... (Comparative Study)
Comparative Study
The mammalian epidermis has evolved to protect the body in a dry environment. Genes of the epidermal differentiation complex (EDC), such as FLG (filaggrin), are implicated in the barrier function of the epidermis. Here, we investigated the molecular evolution of the EDC in sirenians (manatees and dugong), which have adapted to fully aquatic life, in comparison to the EDC of terrestrial mammals and aquatic mammals of the clade Cetacea (whales and dolphins). We show that the main subtypes of EDC genes are conserved or even duplicated, like late cornified envelope (LCE) genes of the dugong, whereas specific EDC genes have undergone inactivating mutations in sirenians. FLG contains premature stop codons in the dugong, and the ortholog of human CASP14 (caspase-14), which proteolytically processes filaggrin, is pseudogenized in the same species. As FLG and CASP14 have also been lost in whales, these mutations represent convergent evolution of skin barrier genes in different lineages of aquatic mammals. In contrast to the dugong, the manatee has retained functional FLG and CASP14 genes. FLG2 (filaggrin 2) is truncated in both species of sirenians investigated. We conclude that the land-to-water transition of sirenians was associated with modifications of the epidermal barrier at the molecular level.
Topics: Animals; Humans; Adaptation, Physiological; Caspase 14; Epidermis; Evolution, Molecular; Filaggrin Proteins; Genomics; Phylogeny
PubMed: 38653760
DOI: 10.1038/s41598-024-60099-2 -
Frontiers in Plant Science 2024
PubMed: 38650706
DOI: 10.3389/fpls.2024.1341528 -
Communications Biology Apr 2024Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform...
Spontaneous cancers in companion dogs are robust models of human disease. Tracking tumor-specific immune responses in these models requires reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). scTCRseq and integration with scRNA data have not been demonstrated on companion dogs with cancer. Here, five healthy dogs, two dogs with T cell lymphoma and four dogs with melanoma are selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. Single-cell suspensions of PBMCs or lymph node aspirates are profiled using scRNA and dog-specific scTCRseq primers. In total, 77,809 V(D)J-expressing cells are detected, with an average of 3498 (348 - 5,971) unique clonotypes identified per sample. In total, 29/34, 40/40, 22/22 and 9/9 known functional TRAV, TRAJ, TRBV and TRBJ gene segments are observed respectively. Pseudogene or otherwise defective gene segments are also detected supporting re-annotation of several as functional. Healthy dogs exhibit highly diverse repertoires, T cell lymphomas exhibit clonal repertoires, and vaccine-treated melanoma dogs are dominated by a small number of highly abundant clonotypes. scRNA libraries define large clusters of V(D)J-expressing CD8+ and CD4 + T cells. Dominant clonotypes observed in melanoma PBMCs are predominantly CD8 + T cells, with activated phenotypes, suggesting possible anti-tumor T cell populations.
Topics: Animals; Dogs; Receptors, Antigen, T-Cell; Single-Cell Analysis; Melanoma; Dog Diseases; Lymphoma, T-Cell
PubMed: 38649520
DOI: 10.1038/s42003-024-06174-w -
Journal of Autoimmunity Jun 2024Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two...
Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed the pseudogene UHRF1P as a novel SLE biomarker. The pseudogene-encoded UHRF1P protein was overexpressed in peripheral blood T cells of SLE patients. The UHRF1P protein lacks the amino-terminus of its parental UHRF1 protein, resulting in missing the proteasome-binding ubiquitin-like (Ubl) domain of UHRF1. T-cell-specific UHRF1P transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHFR1P prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF1P transgenic mice were obliterated by MAP4K3 knockout. Collectively, UHRF1P overexpression in T cells inhibits the E3 ligase function of its parental UHRF1 and induces autoimmune diseases.
Topics: Lupus Erythematosus, Systemic; Animals; Interleukin-17; Ubiquitin-Protein Ligases; Humans; Mice; CCAAT-Enhancer-Binding Proteins; Mice, Transgenic; Protein Serine-Threonine Kinases; Ubiquitination; Mice, Knockout; Disease Models, Animal; Signal Transduction; T-Lymphocytes; Autoimmunity; Female
PubMed: 38643728
DOI: 10.1016/j.jaut.2024.103221 -
IScience Apr 2024A quarter of marine mammals are at risk of extinction, with disease and poor habitat quality contributing to population decline. Investigation of the Major...
A quarter of marine mammals are at risk of extinction, with disease and poor habitat quality contributing to population decline. Investigation of the Major Histocompatibility Complex (MHC) provides insight into species' capacity to respond to immune and environmental challenges. The eighteen available cetacean chromosome level genomes were used to annotate MHC Class I loci, and to reconstruct the phylogenetic relationship of the described loci. The highest number of loci was observed in the striped dolphin (), while the least was observed in the pygmy sperm whale () and rough toothed dolphin (). Of the species studied, Mysticetes had the most pseudogenes. Evolutionarily, MHC Class I diverged before the speciation of cetaceans. Yet, locus one was genomically and phylogenetically similar in many species, persisting over evolutionary time. This characterisation of MHC Class I in cetaceans lays the groundwork for future population genetics and MHC expression studies.
PubMed: 38632986
DOI: 10.1016/j.isci.2024.109590 -
Microbial Genomics Apr 2024(Enterobacterales: Erwiniaceae) are a group of cosmopolitan bacteria best known as the causative agents of various plant diseases. However, other species in this genus...
(Enterobacterales: Erwiniaceae) are a group of cosmopolitan bacteria best known as the causative agents of various plant diseases. However, other species in this genus have been found to play important roles as insect endosymbionts supplementing the diet of their hosts. Here, I describe Erwinia impunctatus (Erwimp) associated with the Highland midge (Diptera: Ceratopogonidae), an abundant biting pest in the Scottish Highlands. The genome of this new species was assembled using hybrid long and short read techniques, and a comparative analysis was undertaken with other members of the genus to understand its potential ecological niche and impact. Genome composition analysis revealed that Erwimp is similar to other endophytic and ectophytic species in the genus and is unlikely to be restricted to its insect host. Evidence for an additional plant host includes the presence of a carotenoid synthesis operon implicated as a virulence factor in plant-associated members in the sister genus . Unique features of Erwimp include several copies of intimin-like proteins which, along with signs of genome pseudogenization and a loss of certain metabolic pathways, suggests an element of host restriction seen elsewhere in the genus. Furthermore, a screening of individuals over two field seasons revealed the absence of the bacteria in during the second year indicating this microbe-insect interaction is likely to be transient. These data suggest that may have an important role to play beyond a biting nuisance, as an insect vector transmitting Erwimp alongside any conferred impacts to surrounding biota.
Topics: Humans; Animals; Ceratopogonidae; Erwinia; Genomics; Insect Vectors; Ecosystem
PubMed: 38630610
DOI: 10.1099/mgen.0.001242 -
PhytoKeys 2024The current article describes , a new species of diatom from Lake Van, a highly alkaline lake in Eastern Anatolia (Türkiye). The description is based on light and...
Description of sp. nov. (Naviculales, Naviculaceae), a new species of diatom from the highly alkaline Lake Van (Republic of Türkiye) with complete characterisation of its organellar genomes and multigene phylogeny.
The current article describes , a new species of diatom from Lake Van, a highly alkaline lake in Eastern Anatolia (Türkiye). The description is based on light and scanning electron microscopy performed on two monoclonal cultures. The complete nuclear rRNA clusters and plastid genomes have been sequenced for these two strains and the complete mitogenome for one of them. The plastome of both strains shows the probable loss of a functional gene. They also exhibit two IB4 group I introns in their , each encoding for a putative LAGLIDADG homing endonuclease, with the first L1917 IB4 intron reported amongst diatoms. The Maximum Likelihood phylogeny inferred from a concatenated alignment of , and distinguishes sp. nov. from the morphologically similar species and .
PubMed: 38628637
DOI: 10.3897/phytokeys.241.118903 -
RNA Biology Jan 2024Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides... (Review)
Review
Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several snoRNAs are now known to regulate diverse levels of gene expression. While these functions are carried out in by mature snoRNAs, evidence has also been emerging of regulatory roles of snoRNAs in , either within their genomic locus or as longer transcription intermediates during their maturation. Herein, we review recent findings that snoRNAs can interact in with their intron to regulate the expression of their host gene. We also explore the ever-growing diversity of longer host-derived snoRNA extensions and their functional impact across the transcriptome. Finally, we discuss the role of snoRNA duplications into forging these new layers of snoRNA-mediated regulation, as well as their involvement in the genomic imprinting of their host locus.
Topics: RNA, Small Nucleolar; RNA, Untranslated; RNA, Ribosomal; Introns
PubMed: 38626213
DOI: 10.1080/15476286.2024.2342685 -
MicroLife 2024Invasive non-typhoidal (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan...
Invasive non-typhoidal (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. serovar Typhimurium ST313 causes the majority of iNTS in Malawi. We performed an intensive comparative genomic analysis of 608 . Typhimurium ST313 isolates dating between 1996 and 2018 from Blantyre, Malawi. We discovered that following the arrival of the well-characterized . Typhimurium ST313 lineage 2 in 1999, two multidrug-resistant variants emerged in Malawi in 2006 and 2008, designated sublineages 2.2 and 2.3, respectively. The majority of . Typhimurium isolates from human bloodstream infections in Malawi now belong to sublineages 2.2 or 2.3. To understand the emergence of the prevalent ST313 sublineage 2.2, we studied two representative strains, D23580 (lineage 2) and D37712 (sublineage 2.2). The chromosome of ST313 lineage 2 and sublineage 2.2 only differed by 29 SNPs/small indels and a 3 kb deletion of a Gifsy-2 prophage region including the pseudogene. Lineage 2 and sublineage 2.2 had distinctive plasmid profiles. The transcriptome was investigated in 15 infection-relevant conditions and within macrophages. During growth in physiological conditions that do not usually trigger . Typhimurium SPI2 gene expression, the SPI2 genes of D37712 were transcriptionally active. We identified down-regulation of flagellar genes in D37712 compared with D23580. Following phenotypic confirmation of transcriptomic differences, we discovered that sublineage 2.2 had increased fitness compared with lineage 2 during mixed growth in minimal media. We speculate that this competitive advantage is contributing to the emergence of sublineage 2.2 in Malawi.
PubMed: 38623411
DOI: 10.1093/femsml/uqae005 -
BMC Genomics Apr 2024Microbial genomes are largely comprised of protein coding sequences, yet some genomes contain many pseudogenes caused by frameshifts or internal stop codons. These...
BACKGROUND
Microbial genomes are largely comprised of protein coding sequences, yet some genomes contain many pseudogenes caused by frameshifts or internal stop codons. These pseudogenes are believed to result from gene degradation during evolution but could also be technical artifacts of genome sequencing or assembly.
RESULTS
Using a combination of observational and experimental data, we show that many putative pseudogenes are attributable to errors that are incorporated into genomes during assembly. Within 126,564 publicly available genomes, we observed that nearly identical genomes often substantially differed in pseudogene counts. Causal inference implicated assembler, sequencing platform, and coverage as likely causative factors. Reassembly of genomes from raw reads confirmed that each variable affects the number of putative pseudogenes in an assembly. Furthermore, simulated sequencing reads corroborated our observations that the quality and quantity of raw data can significantly impact the number of pseudogenes in an assembler dependent fashion. The number of unexpected pseudogenes due to internal stops was highly correlated (R = 0.96) with average nucleotide identity to the ground truth genome, implying relative pseudogene counts can be used as a proxy for overall assembly correctness. Applying our method to assemblies in RefSeq resulted in rejection of 3.6% of assemblies due to significantly elevated pseudogene counts. Reassembly from real reads obtained from high coverage genomes showed considerable variability in spurious pseudogenes beyond that observed with simulated reads, reinforcing the finding that high coverage is necessary to mitigate assembly errors.
CONCLUSIONS
Collectively, these results demonstrate that many pseudogenes in microbial genome assemblies are actually genes. Our results suggest that high read coverage is required for correct assembly and indicate an inflated number of pseudogenes due to internal stops is indicative of poor overall assembly quality.
Topics: Pseudogenes; Chromosome Mapping; Genome, Bacterial; Base Sequence; Genome, Microbial; Sequence Analysis, DNA; High-Throughput Nucleotide Sequencing
PubMed: 38622536
DOI: 10.1186/s12864-024-10137-0