Biology subjects

Paces, J.

Publications and source records attributed to Paces, J..

7 recordsLinked to original sources

bioRxiv2026

Stable but turbulent: the two faces of the germline-restricted chromosome of passerine birds

Germline-restricted chromosomes (GRCs) are essential, supernumerary chromosomes that undergo programmed elimination in somatic cells and are only retained in the germline. Despite their recurrent emergence across animals, their genetic composition, function and evolution remain poorly understood. Here we present the most complete and contiguous GRC assemblies, including one nearly telomere-to-telomere GRC assembly, from four closely related passerine bird species, providing an unprecedented insight into the GRCs composition and its evolution over short evolutionary timescales. We show that the passerine GRC is highly enriched in repetitive sequences, with massive, species-specific satellite expansions resulting in enormous differences in GRC size among species. Among mostly recently added sequences, we found only two ancestral genes dating back to the presumed GRC origin, offering clues to its essential function. Importantly, we demonstrate that the GRC undergoes extensive fine-scale within-chromosome rearrangements and copy number changes resulting in little collinearity between species. Our findings indicate that programmed DNA elimination has profoundly changed the GRCs evolution by altering the selection pressures and mutational mechanisms it is exposed to. This makes the GRC an extraordinarily dynamic element in an otherwise stable avian karyotype, retaining core functions while diversifying rapidly, with important implications for germline biology, adaptive evolution and speciation.

evolutionary biology↗

bioRxiv2025

Decoding the avian missing gene mystery: dot chromosomes unmask extensive gene loss and novel genetic instability

The apparent absence of numerous conserved vertebrate genes from avian genomes has puzzled researchers for over a decade. In recent years, a subset of these genes has been identified; however, their sequences are unusually problematic, often evading detection by standard sequencing technologies. This limitation has hindered detailed investigation of the phenomenon--until recent progress in long read technologies, which are more robust against sequencing biases. This enabled us to classify real gene losses extensively, which strikingly revealed that a large number of the genes residing on so-called dot chromosomes were indeed lost during avian evolution. We demonstrate that dot microchromosomes--small, repeat-dense avian chromosomes--harbor widespread gene attrition, with 29% of ohnologs (duplicates from ancestral genome doublings) eliminated, far exceeding rates on other chromosomes. Moreover, we reveal that genes retained on these dot chromosomes exhibit a previously undescribed form of dynamic genetic instability. This instability, which we term sequence stuttering, is characterized by a massive expansion of short sequences within intronic regions. Intriguingly, in some cases, the expanding sequences appear to originate from neighboring exons. As a result, intron lengths vary extensively among individual chickens, suggesting that these events are evolutionarily recent. Since this phenomenon has not been reported in any other vertebrate species, our findings lay the groundwork for future research into its underlying mechanisms, evolutionary implications, and potential identification of similar loci across vertebrate genomes. SIGNIFICANCEThis study reveals extensive gene loss and a novel genetic instability, termed "sequence stuttering," on avian dot microchromosomes, providing new insights into avian genomic evolution. Approximately 29% of ohnologs on dot chromosomes are absent compared to other vertebrate chromosomes, possibly due to elevated GC content and recombination rates in euchromatin regions. This significant gene loss highlights dot chromosomes as hotspots for genomic reduction, potentially shaping avian-specific traits. Additionally, sequence stuttering--characterized by extensive intronic repeat expansions, sometimes incorporating exonic sequences--introduces marked length polymorphism within chicken populations, suggesting ongoing evolutionary dynamics. These findings underscore the unique role of dot chromosomes in avian genome evolution, emphasizing their contribution to genetic diversity and adaptation. This work lays the foundation for further investigation into the molecular mechanisms driving these phenomena and their broader implications for vertebrate genomic evolution.

genomics↗

bioRxiv2025

Sex Chromosome Turnover and Structural Interspecific Genome Divergence Shapes Meiotic Outcomes in Hybridizing Cobitis

It has been empirically established that genome mixing between divergent species can trigger meiotic aberrations, ultimately leading to the emergence of asexual reproduction through the production of unreduced gametes in various metazoan lineages. Yet, it remains poorly understood how such asexual hybrids cope with co-inherited differences in sex determination systems, diverged regulatory networks, and chromosomal incompatibilities-- especially in the context of increased ploidy. Addressing these questions requires high-quality, chromosome-level reference genomes of the parental species involved in hybrid formation. Here, we present the first chromosome-level genome assemblies for three hybridizing Cobitis species (C. elongatoides, C. taenia, and C. tanaitica), providing a comprehensive framework to investigate the genetic and cytogenetic basis of hybrid sterility and the transition to asexuality. By integrating genome scaffolding, male/female pooled sequencing, and molecular cytogenetics, we uncover extensive structural variation among homologous chromosomes of the three species, despite their overall syntenic conservation. Population-level Pool-Seq analyses further revealed that each species possesses a distinct, non-homologous sex chromosome, highlighting sex chromosome turnover even among recently diverged lineages. These assemblies enabled the design of chromosome-specific painting probes, which we applied to meiotic metaphase I spreads of diploid hybrids. This approach revealed striking differences in the pairing success of orthologous chromosomes, with some (e.g., Ch01B) frequently forming bivalents, while others (e.g., Ch01A, Ch05, Ch20) failed to do so and remained unpaired. Our results demonstrate that chromosome-specific features, shaped by structural evolution and sex-linked divergence, contribute unequally to hybrid meiotic failure. Together, this work provides a high-resolution genomic and cytogenetic framework to understand how interspecific hybridization gives rise to clonality, and how the architecture of inherited parental genomes shapes the success or breakdown of meiosis in hybrid vertebrates.

genomics↗

bioRxiv2025

Claudin 1-mediated positioning of DC1 to mTECs is essential for antigen transfer-coupled DC1 maturation and maintenance of central tolerance

The mechanisms of central tolerance, which rely on the presentation of self-antigens by medullary thymic epithelial cells (mTECs) and DCs, prevent autoimmunity by eliminating self-reactive T-cells. While mTECs produce self-antigens in an autonomous manner, DCs acquire them from mTECs via cooperative antigen transfer (CAT). Our recent data showed that preferential pairing occurs between distinct subsets of mTECs and DCs in CAT, providing a rationale for the existence of molecular determinants which control such pairing and the outcome of central tolerance. Here, we compared the transcriptomes of CAT-experienced and -inexperienced DCs and identified Claudin 1 as a molecule involved in CAT-coupled type 1 DC (DC1) maturation. By mapping thymic DC1 heterogeneity, we identified their early and late maturation states. DC1-specific ablation of Claudin 1 led to a reduction in CAT-experienced late mature DC1s and hampered DC1 maturation. These phenotypes correlated with the displacement of DC1s from the vicinity of mTECs. This translated into impaired Treg selection and clonal deletion of TRA-specific T-cells manifested via a break in tolerance and symptoms of multi-organ autoimmunity. Collectively, our results identify thymic DC1-derived Claudin 1 as a regulator of immune tolerance. One Sentence SummaryThe expression of Claudin 1 on type 1 dendritic cells regulates their proximity to mTECs, which is required for effective antigen transfer coupled with DC1 maturation and establishment of T-cell tolerance.

immunology↗

bioRxiv2024

Cell type and regulatory analysis in amphioxus illuminates evolutionary origin of the vertebrate head

To shed light on the enigmatic origin of the vertebrate head, our study employs an integrated approach that combines single-cell transcriptomics, perturbations in signalling pathways, and cis-regulatory analysis in amphioxus, a close relative of chordate common ancestor. Through cell type characterization, we identified the presence of a prechordal plate, pre-migratory and migratory neural crest-like cell populations in the developing amphioxus embryo. Functional analysis established conserved roles of the Nodal and Hedgehog signalling pathways in prechordal plate, and of Wnt signalling pathway in neural crest development. Furthermore, the trans-species transgenic experiments provided evidence of cis-regulatory level homology within the chordate lineage. Our findings provide evidence that the key features of vertebrate head development can be traced back to the common ancestor of all chordates. One Sentence SummaryCell populations forming the vertebrate head are present in the close relative of chordate common ancestor.

evolutionary biology↗

bioRxiv2023

Chromatin remodeling enzyme Snf2h is essential for retinal cell proliferation and photoreceptor maintenance

Chromatin remodeling complexes are required for many distinct nuclear processes such as transcription, DNA replication and DNA repair. However, how these complexes contribute to the development of complex tissues within an organism is poorly characterized. Imitation switch (ISWI) proteins are among the most evolutionarily conserved ATP-dependent chromatin remodeling factors and are represented by yeast Isw1/Isw2, and their vertebrate counterparts Snf2h (Smarca5) and Snf2l (Smarca1). In this study, we focused on the role of the Snf2h gene during development of the mammalian retina. We show that Snf2h is expressed in both retinal progenitors and post-mitotic retinal cells. Using Snf2h conditional knockout mice (Snf2h cKO), we found that when Snf2h is deleted the laminar structure of the adult retina is not retained, the overall thickness of the retina is significantly reduced compared with controls, and the outer nuclear layer (ONL) is completely missing. Depletion of Snf2h did not influence the ability of retinal progenitors to generate all of the differentiated retinal cell types. Instead, Snf2h function is critical for proliferation of retinal progenitor cells. Cells lacking Snf2h have a defective S-phase, leading to the entire cell division process impairments. Although, all retinal cell types appear to be specified in the absence of Snf2h function, cell cycle defects and concomitantly increased apoptosis in Snf2h cKO result in abnormal retina lamination, complete destruction of the photoreceptor layer and, consequently, in a physiologically non-functional retina.

developmental biology↗

bioRxiv2022

HIV-1 infection reduces NAD capping of host cell snRNA and snoRNA

Nicotinamide adenine dinucleotide (NAD) is a critical component of the cellular metabolism and also serves as an alternative 5' cap on various RNAs. However, the function of the NAD RNA cap is still under investigation. We studied NAD capping of RNAs in HIV-1-infected cells because HIV-1 is responsible for the depletion of the NAD/NADH cellular pool and causing intracellular pellagra. By applying the NAD captureSeq protocol to HIV-1-infected and uninfected cells, we revealed that four snRNAs (e.g. U1) and four snoRNAs lost their NAD cap when infected with HIV-1. Here, we provide evidence that the presence of the NAD cap decreases the stability of the U1/HIV-1 pre-mRNA duplex. Additionally, we demonstrate that reducing the quantity of NAD-capped RNA by overexpressing the NAD RNA decapping enzyme DXO results in an increase in HIV-1 infectivity. This suggests that NAD capping is unfavorable for HIV-1 and plays a role in its infectivity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/515957v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@16d5cf0org.highwire.dtl.DTLVardef@f0bc60org.highwire.dtl.DTLVardef@df83bborg.highwire.dtl.DTLVardef@41a2db_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗