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Cohort-HMM marker recruitment with per-OG orthology QC for phylogenomic supermatrices

OrthoFinder's all-vs-all DIAMOND step systematically misses single-copy orthogroups (SC OGs) at deep taxonomic divergence: a marker recovered cleanly within a tightly defined cohort is dropped when the same marker is searched against phylum-broad metagenome-assembled genome (MAG) sets, because pairwise sequence similarity falls below DIAMOND's detection threshold even when the underlying ortholog is present. The result is biased dropout - supermatrices that retain genomes near the cohort but...

bioRxiv 10d ago

GCK-4 regulates apical actin organization and lumen formation in the C. elegans intestine

Epithelial tubes are an essential component of many organ systems. The formation of their lumens depends on the close coordination of epithelial polarity, the apical actin cytoskeleton, and apical junctions, yet the mechanisms that organize the apical cytoskeleton and junctions downstream of polarity remain poorly understood. Here, we identify the Ste20 family kinase GCK-4, the single C. elegans ortholog of the mammalian kinases LOK and SLK, as a critical regulator of intestinal lumen formation.

bioRxiv 2d ago

In vivo functional classification of PTEN variants reveals context-dependent oncogenicity and interindividual variability

Gene variants, secondary mutations, and stochastic individual variability complicate cancer diagnosis, prognosis, and treatments. Here, we systematically assess the functional impact of PTEN cancer-related missense mutations in mammalian cell lines, yeast, and Caenorhabditis elegans. While cell-based assays revealed alterations in lipid phosphatase activity, CRISPR-based engineering of orthologous mutations in C. elegans enabled classification of variants based on organismal phenotypes and...

bioRxiv 2d ago

Molecular Basis of Histone H3 Reading and Writing by Legionella pneumophila SET Domain Lysine Methyltransferases

RomA and its highly conserved strain ortholog LegAS4 are SET and ankyrin domain-containing effector proteins of the intracellular bacterial pathogen Legionella pneumophila. These enzymes are secreted into host cells, where they translocate to the nucleus and methylate Lys14 in histone H3 (H3K14), a novel post-translation modification (PTM) that reprograms gene expression and promotes bacterial replication. To elucidate their H3K14 substrate specificity, we determined the crystal structures...

bioRxiv 11d ago

Using protein language models for pangenome construction

Current pangenome construction methods rely largely on nucleotide or protein sequence alignment, limiting their ability to detect remote orthologs and semantic relations. We introduce a novel method that leverages protein language model embeddings to capture functional and semantic relationships beyond sequence similarity. Our approach employs approximate nearest-neighbor search coupled with a clustering step utilizing HDBSCAN, DBSCAN, or weighted single-linkage clustering with multiple...

bioRxiv 4d ago

Gene ancestries reveal diverse microbial associations during eukaryogenesis

Abstract The origin of eukaryotes remains a central enigma in biology1. Continuing debates agree on the pivotal role of a symbiosis between an alphaproteobacterium and an Asgard archaeon2,3. However, the nature, timing and contributions of other potential bacterial partners4,5,6 and the role of interactions with viruses7,8,9 remain contentious.

Nature 18h ago

Whole-genome duplication shaped cell-type evolution in the vertebrate brain

Abstract The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show...

Nature 18h ago

Segmentation gene expression and function in Vanessa cardui, an emerging model for Lepidoptera

Although all insects are segmented, the genes that control this process vary across species. Many of the pair-rule (PR) genes that direct segment formation in Drosophila are similarly utilized in other holometabolous insects, but more distantly related species use different genes for PR-patterning. Previously, we showed that Lepidoptera lack a highly conserved PR-gene, paired.

bioRxiv 7d ago

Longitudinal RNA Seq analyses reveal the prominent role of Vagococcus in broiler meat spoilage microbiome

Background Raw broiler meat products are highly perishable, and microbial activity is the main factor limiting their shelf lives. The spoilage microbiomes of broiler meat products have been studied mainly using traditional culturing methods and 16S rRNA gene amplicon sequencing, neither of which can show the activity of whole microbiome. Previous metatranscriptomic research of broiler spoilage has also remained limited to specific spoilage organisms rather than entire microbiomes.

bioRxiv 5d ago

Divergent evolution of the PRPS enzymes across the tree of life

The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme plays a central role in core biochemical pathways across all life, reflecting its deep evolutionary significance. Here, we present a pan-domain analysis of more than 35,000 non-redundant protein sequences that defines the fundamental features of PRPS at the roots of both domains of life and at critical branchpoints in the tree of life, including during early eukaryogenesis. Combining protein language modeling with maximum likelihood...

bioRxiv 7d ago