Biology subjects

Suh, A.

Publications and source records attributed to Suh, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Evidence of two centromeres in the germline-restricted chromosome (GRC): insights from zebra finch lampbrush chromosomes

The germline-restricted chromosome (GRC) of the zebra finch Taeniopygia guttata represents a well-established model of programmed DNA elimination in vertebrates. Although the DNA composition of the GRC, as well as elimination processes during spermatogenesis and early embryogenesis, have been characterised previously, little is known about the cytogenetic features underlying its unusual behaviour, including its stable transmission through the maternal germline. Here, we provide a detailed characterisation of the zebra finch GRC at the diplotene stage of female meiosis, when chromosomes are actively transcribed and acquire the form of giant lampbrushes. We identified a transcriptionally repressed region on the GRC, which we term the belt. Microdissection and sequencing of the belt revealed that it is predominantly composed of a tandem repeat derived from the dph6 gene, robo1 gene fragments, and ERVs. Notably, the terminally located functional centromere of the GRC lacks typical zebra finch centromeric satellites and, conversely, consists of the newly identified GRC-specific tandem repeats Tgut16-201 and Tgut17-167. The canonical centromeric repeat Tgut716 was observed in the GRC belts. Moreover, belts, like the terminal GRC centromere, were associated with coilin-containing nuclear bodies, which serve as markers of centromeric regions on zebra finch lampbrush chromosomes. Together, our findings provide evidence for the presence of one functional and one putative centromeric region on the zebra finch GRC, suggesting their role in non-Mendelian inheritance of the GRC. Author summaryGermline-restricted chromosomes (GRCs) are unusual chromosomes that are retained in germ cells but eliminated from somatic cells during early development. They have evolved independently in several groups of organisms, but are particularly notable in passerine birds, a large monophyletic vertebrate clade ([~]6,700 species) in which GRCs have persisted for at least 44 million years. Passerine GRCs are normally transmitted to the next generation through the maternal germ cell, however, the mechanisms ensuring their inheritance remain unknown. To address this question, we examined the structure of the zebra finch GRC during female meiosis. We found that the GRC differs from all other chromosomes in possessing two distinct centromeric regions: a functional terminal centromere and an extended heterochromatic region exhibiting centromeric properties. These unusual features suggest a mechanism by which the GRC may achieve its preferential transmission through the female germline. Our findings substantially advance the understanding of the zebra finch GRC and the general biology of passerine GRCs. By revealing chromosome features that may underlie their non-Mendelian inheritance, this work provides new insights into the evolution and behaviour of GRCs and other selfish chromosomes that bias their own transmission.

genetics↗

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↗

bioRxiv2026

TACE reprograms RANKL-mediated differentiation of macrophages by activating the non-canonical pathway of IRF3

Inflammation is associated with an influx of inflammatory macrophages and increased activation and differentiation of osteoclasts. Receptor activator of NF-kB ligand (RANKL) is a key driver for osteoclast differentiation. However, the pathogenic mechanisms augmenting RANKL-induced osteoclast differentiation in inflammatory conditions are not fully elucidated. Here, we show that TNF- converting enzyme (TACE) plays a critical role in pathological bone erosion and enhances osteoclast differentiation in inflammatory conditions. Myeloid cell-specific TACE deletion in a murine arthritis model attenuates joint inflammation and bone destruction. TACE deficiency suppresses distal RANKL signaling in macrophages by increasing IRF3 activation, while enhancing proximal RANKL signaling, leading to the suppression of osteoclast differentiation. Mechanistically, IRF3 activation limits macrophage reprogramming by suppressing NFATc1 and HB-EGF in response to RANKL through a non-canonical pathway. HB-EGF, a TACE substrate, activates EGFR signaling and promotes osteoclastogenesis by inhibiting IRF3 activation. TACE regulates the reciprocal inhibition of the IRF3-HBEGF axis. Our study highlights a role for TACE as a rheostat, balancing both pro- and anti-osteoclastogenic signals.

cell biology↗

bioRxiv2026

Transposable element activity and polymorphisms drive structural variability within and between individual in bivalves

Structural variants (SVs) represent one of the most abundant sources of genetic variation across eukaryotes, with transposable elements (TEs) standing out as primary contributors in their emergence. While the growing availability of chromosome-scale genomes has revealed the central role of SVs in species diversification and adaptation, non-model invertebrates remain critically understudied in this context. Here, we explore how SVs and their interaction with TEs shape genetic diversity at both the individual and population levels. To achieve this, we leverage four high-quality oyster genomes and a large-scale dataset of the Estuarine oyster (Crassostrea ariakensis) collected across a wide range of different temperature and salinity conditions. We explicitly account for strengths and limitations of current SV-calling software, and benchmark our results through simulations. We uncover pervasive within-individual structural variability, with up to 14% of oyster genome basepairs being in an hemizygous state. The strong enrichment of TEs within these SVs is driven by a prevalence of insertions over deletions, reflecting population-level TE activity. Strikingly, both SVs and de novo TE insertions -- driven by the concurrent mobilization of diverse TE families -- segregate among C. ariakensis populations and contribute to genomic differentiation associated with local adaptation to contrasting sea salinity and temperature levels. Our study demonstrates the power of integrating long- and short-read sequencing to recover a high-confidence catalogue of SVs and de novo TE insertions, and provides empirical evidence that structural variation is an active evolutionary force generating potentially adaptive genetic variation in a key lineage of ecologically and economically important bivalves.

evolutionary biology↗

bioRxiv2025

The germline-restricted chromosome orchestrates germ cell development in passerine birds

While the definition of germ cell fate has been extensively studied in model organisms, evolutionary innovations and mechanistic novelties may remain hidden in understudied systems. The phenomenon of programmed DNA elimination allows germ cells to acquire germline-restricted genes, offering a novel paradigm of germ cell specificity. In passerine birds, the germline-restricted chromosome (GRC) is eliminated from somatic cells in early embryogenesis, yet the role and consequences of its maintenance in the germ cells remain poorly understood. Here, using the zebra finch Taeniopygia guttata as a model, we combined RNA-seq and Spatial Transcriptomics to construct a high-resolution spatiotemporal expression map to understand the role of the GRC across germ cell development. We found a GRC-linked integrin-BMP signaling in maturing oocytes and tfebGRC upregulation at blastoderm embryos, suggesting the involvement of the GRC in oocyte maturation and germ cell determination. We also identified developmental specialization of GRC-linked gene expression relative to their paralogs on the autosomes and sex chromosomes, revealing a gene repertoire which promotes germline stemness and germline/soma distinction. Together, the passerine GRC constitutes a unique system that manifests germ cell complexity, whilst allowing pinpointing the effects on gene expression that may elucidate vertebrate germ cell fate.

developmental biology↗

bioRxiv2025

The complete genome of a songbird

Bird genomes are the smallest among amniotes, but remain challenging to assemble due to their structural complexity. This study presents the first fully phased, diploid, telomere-to-telomere (T2T) reference genome for the zebra finch (Taeniopygia guttata), a model organism for neuroscience and evolutionary genomics. Combining multiple sequencing strategies resulted in closing nearly all gaps, adding [~]90 Mbp of previously missing sequence (7.8%). This includes T2T assemblies for all microchromosomes, including dot chromosomes, and the previously almost entirely missing chr16. The T2T genome is comprehensively annotated for genes, repeats, structural variants, and long-read methylation calls. Complete centromeric structures were assembled and annotated along with kinetochore binding sites. Relative to the previous high-quality reference of the Vertebrate Genomes Project, 2,778 (8.51%) previously unassembled or unannotated genes were identified, of which 9% overlap with segmental duplications. This first complete genome of a songbird, now the new public reference, illuminates avian genome architecture and function.

genomics↗

bioRxiv2025

Retrocopy formation and domestication shape genome evolution in sloths and other xenarthrans

Xenarthrans, comprising sloths, anteaters, and armadillos, represent one of the most morphologically and physiologically specialised mammalian clades, yet the genomic basis of their adaptations remains poorly understood. Here, we present chromosome-level genomes for the two-toed sloth (Choloepus didactylus) and the southern anteater (Tamandua tetradactyla), and investigate how retrotransposon-mediated gene duplications (retrocopies) have shaped xenarthran genome evolution. Comparative analyses revealed that xenarthran genomes harbor the highest number of retrocopies reported among mammals, with lineage-specific insertion dynamics. Anteater and armadillo genomes contain older LINE1 repertoires and species-specific older retrocopy insertions. In contrast, sloths retain both an abundance of young LINE1s and thousands of young retrocopies, alongside a large shared set that originated from an evolutionary burst of retroduplication in the branch leading to their last common ancestor ([~]30 Mya). In C. didactylus, approximately 50% of retrocopies are expressed, compared with 24% in Dasypus novemcinctus. Evolutionary analyses identified 38 retrocopies with strong hallmarks of domestication in C. didactylus. Many of these retrocopies derive from parental genes involved in mitochondrial and metabolic processes, suggesting a genomic mechanism underlying the physiological specialisations of sloths. Altogether, our findings identify retrotransposition as a major contributor to the genomic architecture of Xenarthra and highlight retrocopy origination as a mechanism for generating lineage-specific novelty and distinctive biological specialisations.

genomics↗

bioRxiv2025

Programmed DNA elimination drives rapid genomic innovation in two thirds of all bird species

Bird genomes are among the most stable in terms of synteny and gene content across vertebrates. However, germline-restricted chromosomes (GRCs) represent a striking exception where programmed DNA elimination confines large-scale genomic changes to the germline. GRCs are known to occur in songbirds (oscines), but have been studied only in a few species of Passerides such as the zebra finch, the key model for passerine genomics. Their presence and evolutionary dynamics in most major passerine lineages remain largely unexplored, with suboscines entirely unexamined by cytogenetic or genomic methods. Here, we present the most comprehensive comparative analysis of GRCs to date, spanning 44 million years of passerine evolution. By generating the first germline reference genomes of an oscine and a suboscine, 22 novel germline draft genomes spanning nearly all major passerine lineages and a germline draft genome of a parrot outgroup, we show that the GRC is likely present in 6,700 passerine species. Our results reveal that the GRC evolves rapidly and distinctly from the standard A chromosomes (autosomes and sex chromosomes), yet retains functionally important, selectively maintained genes. We observed gene and repeat turnover occuring orders of magnitude faster than on the A chromosomes. Some GRC genes, such as cpeb1 and pim1, are widespread from an ancient duplication. In contrast, other GRC genes, like mfsd2b and bmp15, have been independently duplicated onto the GRC multiple times, suggesting adaptive constraints. The discovery of zglp1 on the zebra finch GRC, initially copied from chromosome 30 and subsequently lost from it, indicates functional replacement, where the GRC permits gene loss from the standard genome. As the GRC harbors the only zglp1 copy in most of the [~]4000 Passerides species, GRC loss would compromise essential germline functions. Our findings establish the GRC as a genomic innovator driving rapid germline evolution. This fact highlights its evolutionary significance for passerine diversification and suggests that programmed DNA elimination may be an overlooked yet phylogenetically widespread mechanism in many understudied animal lineages.

genomics↗

bioRxiv2025

Targeted Inhibition of Translation Initiation via 2'O-Methylation of Start Codons

Translation initiation involves a concerted set of intermolecular interactions that efficiently recognize optimal AUG start codons. However, translation initiation complexes often start at upstream non-optimal AUGs or near-cognate codons, leading to the expression of upstream Open Reading Frames (uORFs). Using retrospective analyses of translation preinitiation cryo-EM structures, we identified putative hydrogen bonds between the 2-OH groups of mRNA start codons with 18S rRNA. Disruption of these interactions using a chemical modification of mRNA, 2-O-methylation (Nm), repressed translation initiation by preventing the preinitiation complex from recognizing start codons. Notably, 2-O-methylation in upstream AUG and near-cognate codons inhibits upstream translation initiation while enhancing the expression of canonical ORFs. These findings revealed a transcript- and site-specific inhibitory role for 2-O-methylation in translation initiation, providing novel insights into the mechanisms of start codon selection in human transcriptomes.

molecular biology↗

bioRxiv2025

Mechanisms and timing of programmed DNA elimination in songbirds

It is commonly assumed that multicellular organisms contain the same genetic information in all the cells of an individual. However, there is a growing list of species in which parts of the genome are removed from some cells of the organism through a process called programmed DNA elimination. In songbirds, an entire chromosome, called the germline-restricted chromosome (GRC), is lost from all somatic cells during early embryonic development. Nevertheless, the mechanisms, timing and consequences of this elimination remain largely unexplored. Here, we studied GRC elimination using two songbird species, the zebra finch (Taeniopygia guttata) and the Bengalese finch (Lonchura domestica), as model systems. We found that chromosome elimination occurs during the cleavage stage and is completed before egg laying and blastoderm formation. Elimination is associated with delayed attachment of the GRC to the mitotic spindle, changes in its histone modifications, and failure of chromatid separation in anaphase. The lagging GRC is then sequestered into a micronucleus with a defective envelope lacking the essential protein lamin B1, where the DNA is fragmented and degraded. Although the genetic basis of GRC elimination remains to be elucidated, our results suggest that changes of the GRC centromere together with epigenetic modifications of histones play a crucial role in GRC elimination from somatic cells. As the timing of elimination coincides with the germline/soma distinction, we propose that GRC elimination may play an important role in this crucial developmental process in songbirds.

genetics↗

bioRxiv2025

Accumulation of a biparentally-inherited Neptune transposable element in natural Killifish hybrids (Fundulus diaphanus X F. heteroclitus)

Transposable elements (TEs) are abundant selfish genetic elements that can mobilize in their host genome, causing DNA damage, mutations and chromosome rearrangements. TE silencing is thus critical, and is initiated by maternally loaded piRNAs, leading to their repression. Consistently, paternally inherited TEs are derepressed in the progeny of Drosophila crosses involving a naive female. TEs have also been found to be derepressed in interspecific crosses, which is proposed to result from suboptimal interactions of piRNA pathway proteins. Fundulus heteroclitus and F. diaphanus hybridize in nature and produce viable and fertile offspring that sometimes reproduce asexually. We characterized the repetitive DNA content of these species and their asexually reproducing hybrids. TE load was slightly higher than expected in hybrids and associated with younger repeats. Two bi-parentally inherited active Neptune subfamilies showed a remarkable [~]3-4-fold accumulation in hybrids. These results are consistent with suboptimal piRNA pathway function, leading to active TE accumulation.

evolutionary biology↗

bioRxiv2025

Germline-restricted chromosome of songbirds has different centromere compared to regular chromosomes

Centromeres are an important part of chromosomes which direct chromosome segregation during cell division. Their modifications can therefore explain the unusual mitotic and meiotic behaviour of certain chromosomes, such as the germline-restricted chromosome (GRC) of songbirds. This chromosome is eliminated from somatic cells during early embryogenesis and later also from male germ cells during spermatogenesis. Although the mechanism of elimination is not yet known, it is possible that it involves a modification of the centromeric sequence on the GRC, resulting in problems with the attachment of this chromosome to the mitotic or meiotic spindle and its lagging during anaphase, which eventually leads to its elimination from the nucleus. However, the repetitive nature and rapid evolution of centromeres make their identification and comparative analysis across species and chromosomes challenging. Here, we used a combination of cytogenetic and genomic approaches to identify the centromeric sequence of two closely related songbird species, the common nightingale (Luscinia megarhynchos) and the thrush nightingale (L. luscinia). We found a 436-bp satellite repeat present in the centromeric regions of all regular chromosomes, making it a strong candidate for the centromeric repeat. This centromeric repeat was highly similar between the two nightingale species. Interestingly, hybridization of the probe to this satellite repeat on meiotic spreads suggested that this repeat is missing on the GRC. Our results indicate that the change of the centromeric sequence may underlie the unusual inheritance and programmed DNA elimination of the GRC in songbirds.

genomics↗

bioRxiv2023

Teaching transposon classification as a means to crowd source the curation of repeat annotation - a tardigrade perspective

The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. However, manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd sourcing efforts could offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Here, we present an example of such crowd sourcing effort developed through both in-person and online courses built around a collaborative peer-reviewed teaching process that can be used as teaching reference guide for similar projects. The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs: A hidden treasure awaits discovery within non-model organisms.

evolutionary biology↗

bioRxiv2022

An annotated chromosome-scale reference genome for Eastern Black-eared Wheatear (Oenanthe melanoleuca)

Pervasive convergent evolution and in part high incidences of hybridization distinguish wheatears (songbirds of the genus Oenanthe) as a versatile system to address questions at the forefront of research on the molecular bases of phenotypic and species diversification. To prepare the genomic resources for this venture, we here generated and annotated a chromosome-scale assembly of the Eastern Black-eared Wheatear (O. melanoleuca). This species is part of the O. hispanica-complex that is characterized by convergent evolution of plumage coloration and high rates of hybridization. The long-read-based male nuclear genome assembly comprises 1.04 Gb in 32 autosomes, the Z chromosome, and the mitogenome. The assembly is highly contiguous (contig N50: 12.6 Mb; scaffold N50: 70 Mb), with 96% of the genome assembled at chromosome level and 96% BUSCO completeness. The nuclear genome was annotated with 18160 protein-coding genes and 30730 mRNAs, and about 10% of the genome consists of repetitive DNA. The annotated chromosome-scale reference genome of Eastern Black-eared Wheatear provides a crucial resource for research into the genomics of adaptation and speciation in an intriguing group of passerines.

genomics↗

bioRxiv2022

Genomic architecture of migration timing in a long-distance migratory songbird

The impact of climate change on spring phenology poses risks to migratory birds, as migration timing is controlled predominantly by endogenous mechanisms. Despite numerous studies on internal cues controlling migration, the underlying genetic basis of migration timing remains largely unknown. We investigated the genetic architecture of migration timing in a long-distance migratory songbird (purple martin, Progne subis subis) by integrating genomic data with an extensive dataset of direct migratory tracks. Our findings show migration has a predictable genetic basis in martins and maps to a region on chromosome 1. This region contains genes that could facilitate nocturnal flights and act as epigenetic modifiers. Additionally, we found that genomic variance explained a higher proportion of historic than recent environmental spring phenology data, which may suggest a reduction in the adaptive potential of migratory behavior in contemporary populations. Overall, these results advance our understanding of the genomic underpinnings of migration timing and could provide context for conservation action.

genomics↗

bioRxiv2022

Abundant Phenotypic Parallelism, Incomplete Lineage Sorting, and Introgression in Open-Habitat Chats

Insights into the processes underpinning convergent evolution advance our understanding of the contributions of ancestral, introgressed, and novel genetic variation to phenotypic evolution. Phylogenomic analyses characterizing genome-wide gene tree heterogeneity can provide first clues about the extent of ILS and of introgression and thereby into the potential of these processes or (in their absence) the need to invoke novel mutations to underpin convergent evolution. Here, we were interested in understanding the processes involved in convergent evolution in open-habitat chats (wheatears of the genus Oenanthe and their relatives). To this end, based on whole-genome resequencing data from 50 taxa of 44 species, we established the species tree, characterized gene tree heterogeneity, and investigated the footprints of ILS and introgression within the latter. The species tree corroborates the pattern of abundant convergent evolution, especially in wheatears. The high levels of gene tree heterogeneity in wheatears are explained by ILS alone only for 30% of internal branches. For multiple branches with high gene tree heterogeneity, D-statistics and phylogenetic networks identified footprints of introgression. Finally, long branches without extensive ILS between clades sporting similar phenotypes provide suggestive evidence for a role of novel mutations in the evolution of these phenotypes. Together, our results suggest that convergent evolution in open-habitat chats involved diverse processes and highlight that phenotypic diversification is often complex and best depicted as a network of interacting lineages.

evolutionary biology↗

bioRxiv2022

The swan genome and transcriptome: its not all black and white

The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related Northern Hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious disease, notably infectious diseases from which Australia has been largely shielded. Indeed, unlike Mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to severe highly pathogenic avian influenza (HPAI). Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. Here, we generate the first chromosome-length annotated black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We used these genomes and transcriptomes, to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to HPAI. We also implicate genetic differences in SLC45A2 in the iconic plumage of the Australian black swan. Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat the survival of the black swan would be in significant peril.

genomics↗

bioRxiv2022

Caecilian genomes reveal molecular basis of adaptation and convergent evolution of limblessness in snakes and caecilians.

We present genome sequences for the caecilians Geotrypetes seraphini (3.8Gb) and Microcaecilia unicolor (4.7Gb), representatives of a limbless, mostly soil-dwelling amphibian clade with reduced eyes, and unique putatively chemosensory tentacles. More than 69% of both genomes are composed of repeats, with retrotransposons the most abundant. We identify 1,150 orthogroups which are unique to caecilians and enriched for functions in olfaction and detection of chemical signals. There are 379 orthogroups with signatures of positive selection on caecilian lineages with roles in organ development and morphogenesis, sensory perception and immunity amongst others. We discover that caecilian genomes are missing the ZRS enhancer of Sonic Hedgehog which is also mutated in snakes. In vivo deletions have shown ZRS is required for limb development in mice, thus revealing a shared molecular target implicated in the independent evolution of limblessness in snakes and caecilians.

evolutionary biology↗