Biology subjects

Adelson, D. L.

Publications and source records attributed to Adelson, D. L..

At least 19 recordsLinked to original sources

bioRxiv2026

Fully Phased Telomere-to-Telomere Assemblies for Thoroughbred Horse and Donkey Haplotypes derived from a Mule Illuminate the Peculiar Evolution of Equid Centromeres

We present telomere-to-telomere genome assemblies of a Thoroughbred horse and a donkey derived from their mule offspring. Now adopted and annotated by NCBI as reference genomes, these assemblies resolve previously inaccessible regions, including satellite arrays, duplications, and telomeres. Equids are known to exhibit an uncoupling between satellite DNA and centromeric function. The completeness of these assemblies enabled annotation of both satellite-based and satellite-free centromeres, as well as non-centromeric satellite loci, revealing notable centromeric plasticity. They also allowed detailed characterization of the variable binding domains of CENP-A--the epigenetic determinant of centromere identity--and CENP-B, whose association with CENP-A, previously considered typical based on a few model organisms, is absent in equids. Comparative analyses of satellite repeats and centromere positions provide new insights into the accelerated karyotypic reshuffling in equid evolution. These assemblies represent foundational resources for equid genomics and support ongoing initiatives such as the Equine Pangenome Project.

molecular biology↗

bioRxiv2026

Molecular Mechanisms Associated With Amelioration Of Radiation Induced Gastrointestinal Mucositis By Compound Kushen Extracts

Radiation induced gastrointestinal mucositis (GIM) is a severe complication of radiotherapy that compromises patient quality of life and treatment efficacy. This study assessed the therapeutic potential and molecular mechanisms of two forms of herbal extracts, Compound Kushen Powder (CKP) and Compound Kushen Injection (CKI) in a rat model of GIM. Administration of either CKP or CKI to irradiated animals significantly reduced the severity of GIM symptoms. Transcriptomic analysis of jejunum and colon mucosa identified candidate mechanisms as well as common pathways between CKP and CKI. CKP modulated innate immune activation and inflammatory signalling, affecting genes such as Socs3 and Tlr4, while CKI promoted tissue repair and oxidative stress resistance through genes including Osm, Epha2, and Stat3. However, both forms of herbal extract enhanced stress response and stimulus regulation in our GIM model. These findings reveal common mechanisms shared by CKP and CKI that suppress symptoms of radiation induced GIM, along with extract specific effects on distinct pathways, acting on different set of genes.

molecular biology↗

bioRxiv2026

Ancient persistence and newfound diversity of CR1-group retrotransposons across chordates

Retrotransposons are mobile, repetitive DNA sequences that are ubiquitous across eukaryotes and widely recognised as key drivers of both gene and genome evolution. The CR1 group of retrotransposons is thought to have been present in the most recent common ancestor of chordates [~]560 mya, and is the dominant retrotransposon in the majority of chordate species. The advent of long-read sequencing technologies has enabled the assembly of high-quality genomes from representatives of almost all major chordate orders, enabling comparative analysis with deeply divergent species. To better understand the composition of CR1-group elements (CGEs) in chordates, we systematically characterised full-length, recently active transposable elements across representative species from every available extant order of chordate. Our analysis uncovered previously unknown phylogenetic relationships of CGEs within and between species and has pushed back the origin of certain CR1-group subclades by tens of millions of years. Additionally, entirely novel elements with no close relatives in existing databases were uncovered within several of the species analysed. We also detected numerous putative horizontal transfer events, many of which had not been previously documented. Overall, this investigation has provided the first chordate-wide analysis of an element that is historically understudied yet plays a pivotal role in genome biology and evolution.

evolutionary biology↗

bioRxiv2025

Lineage-Specific Evolution, Structural Diversity, and Activity of R2 Retrotransposons in Animals

Retrotransposons play outsized roles in the evolution of gene regulation, genome function, and disease pathogenesis and more recently, have sparked interest as workhorses for new gene therapy approaches. R2 retrotransposons insert site-specifically to the multicopy genes encoding 28S ribosomal RNA at a target sequence conserved broadly across eukaryotic evolution. R2 retrotransposons have been detected in many animals, but previous surveys have been limited in scope and methodology. Here, we substantially expand the known distribution of R2 retrotransposons from previously unrepresented or underrepresented taxonomic groups ranging from ctenophores to amphibians and reptiles. We discover diverse R2 domain architectures and motifs and identify many new avian R2 candidates for genome engineering development. Overall, phylogenetic analyses reveal two highly successful R2 lineages. We observe properties of each lineage in several features of the domains that mediate DNA recognition and in co-evolving signatures within the reverse transcriptase domain. Within each of the two lineages, R2 protein sequences do not necessarily preserve the unifying configuration of N-terminal DNA-binding domains implied in the current clade classification scheme. We show that recombinant R2 proteins with distinctive domain architectures and distribution across major animal classes support target-primed reverse transcription with conserved site specificity. Our analysis of the surprisingly varied domain architectures that support target-site specificity informs new R2 classification criteria and provides a greatly expanded foundation for additional structure/function insights about DNA binding selectivity. This expanded perspective on R2 evolution informs approaches for engineering therapeutic gene insertion technologies and offers an opportunity to investigate the conservation and diversification of retrotransposons.

evolutionary biology↗

bioRxiv2024

Structures of vertebrate R2 retrotransposon complexes during target-primed reverse transcription and after second strand nicking

R2 retrotransposons are model site-specific eukaryotic non-LTR retrotransposons that copy-and-paste into gene loci encoding ribosomal RNAs. Recently we demonstrated that avian A-clade R2 proteins achieve efficient and precise insertion of transgenes into their native safe-harbor loci in human cells. The features of A-clade R2 proteins that support gene insertion are not characterized. Here, we report high resolution cryo-electron microscopy structures of two vertebrate A-clade R2 proteins, avian and testudine, at the initiation of target-primed reverse transcription and one structure after cDNA synthesis and second strand nicking. Using biochemical and cellular assays we discover the basis for high selectivity of template use and unique roles for each of the expanded A-clade zinc-finger domains in nucleic acid recognition. Reverse transcriptase active site architecture is reinforced by an unanticipated insertion motif in vertebrate A-clade R2 proteins. Our work brings first insights to A-clade R2 protein structure during gene insertion and enables further improvement and adaptation of R2-based systems for precise transgene insertion.

biochemistry↗

bioRxiv2024

Validating the Target Functions and Synergistic Multi-Target, Multi-Pathway Action Mode of Compound Kushen Injection Using CRISPR/CAS

Background and PurposeDue to the complexity of traditional Chinese medicine based on complex mixtures of natural products and their multi-target mechanism of action, the discovery and validation of relevant targets have always been challenging. In previous studies, using transcriptomic methods and Compound Kushen Injection (CKI) as a model drug, we identified multiple pathways and target genes through which CKI exerts its pharmacological effects. Therefore, we wished to verify these targets by perturbing those genetic pathways. Experimental ApproachIn this study, we selected eight key genes from four candidate pathways and used CRISPR/CAS technology to knock out these genes in four cell lines, validating their role in CKI activity. Key ResultsFirstly, we found that although the sensitivity of different cell lines to gene knockout varied, overall, it led to a reduction in various cellular activities. After the addition of CKI, we observed that, except for the minor impact of CDKN1A gene knockout on the effect of CKI, knocking out the other genes significantly affected the pharmacological efficacy of CKI in different assays. Among them, knockout of MYD88 and NFkB genes enhanced the efficacy of CKI. At the same time, we found that the genes IL24 and CYP1B1 play a crucial role in CKI inhibition of tumour cell migration, and the CYP1A1 gene is critical for the cell cycle arrest induced by CKI. Conclusion and ImplicationsThese findings not only validate the results of our previous transcriptomic analysis but also further demonstrate the complexity of pharmacological mechanisms of multi-target synergistic action of natural product mixtures. What is already knownCKI demonstrates antitumor effects in both clinical and pharmacological research. Transcriptomic analysis shows CKI can perturb the expression of numerous genes in pathways related to cancer. What does this study addThe knockout of most selected genes whose expression is altered by CKI can significantly affect the pharmacological effects of CKI. IL24 and CYP1B1genes are essential to CKIs inhibition of cancer cell migration and CYP1A1 is important for CKIs G2M cell cycle arrest effect. What is the clinical significanceThe efficacy of CKI is demonstrated to arise from the synergistic action of multiple pathways and targets.

pharmacology and toxicology↗

bioRxiv2023

Jumping between Turtles, Fishes, and a Frog: The Unexpected Horizontal Transfer of a DNA Transposon

Horizontal transfer of transposable elements (HTT) has been reported across many species and the impact of such events on genome structure and function has been well described. However, few studies have focused on reptilian genomes, especially HTT events in Testudines (turtles). Here, we investigated the repetitive content of Malaclemys terrapin terrapin (Diamondback turtle) and found a high similarity hAT-6 DNA transposon shared between other turtle species, ray-finned fishes, and a frog. hAT-6 was notably absent in taxa closely related to turtles, such as crocodiles and birds. Successful invasion of DNA transposons into new genomes requires the conservation of specific residues in the encoded transposase, and through structural analysis, these residues were identified indicating retention of functional transposition activity. We document a rare and recent HTT event of a DNA transposon between turtles which are known to have a low genomic evolutionary rate and ancient repeats.

evolutionary biology↗

bioRxiv2023

The genome of medicinal plant Sophora flavescens has undergone significant expansion of both transposons and genes.

PurposeSophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). However, there is little genomic information available for S. flavescens. MethodsIn this study, we used third-generation Nanopore long-read sequencing technology combined with Hi-C scaffolding technology to de novo assemble the S. flavescens genome. ResultsWe obtained a chromosomal level high-quality S. flavescens draft genome. The draft genome size is approximately 2.08 Gb, with more than 80% annotated as Transposable Elements (TEs), which have recently and rapidly proliferated. This genome size is [~]5x larger than its closest sequenced relative Lupinus albus l.. We annotated 60,485 genes and examined their expression profiles in leaf, stem and root tissues, and also characterised the genes and pathways involved in the biosynthesis of major bioactive compounds, including alkaloids, flavonoids and isoflavonoids. ConclusionThe assembled genome highlights the very different evolutionary trajectories that have occurred in recently diverged Fabaceae, leading to smaller duplicated genomes vs larger genomes resulting from TE expansion. Our assembly provides valuable resources for conservation, genetic research and breeding of S. flavescens.

genomics↗

bioRxiv2023

Differential allelic representation (DAR) identifies candidate eQTLs and improves transcriptome analysis

In comparisons between mutant and wild-type genotypes, transcriptome analysis can reveal the direct impacts of a mutation, together with the homeostatic responses of the biological system. Recent studies have highlighted that, when homozygous mutations are studied in non-isogenic backgrounds, genes from the same chromosome as a mutation often appear over-represented among differentially expressed (DE) genes. One hypothesis suggests that DE genes chromosomally linked to a mutation may not reflect true biological responses to the mutation but, instead, result from differences in representation of expression quantitative trait loci (eQTLs) between sample groups selected on the basis of mutant or wild-type genotype. This is problematic when inclusion of spurious DE genes in a functional enrichment study results in incorrect inferences of mutation effect. Here we show that chromosomally co-located differentially expressed genes (CC-DEGs) can also be observed in analyses of dominant mutations in heterozygotes. We define a method and a metric to quantify, in RNA-sequencing data, localised differential allelic representation (DAR) between groups of samples subject to differential expression analysis. We show how the DAR metric can predict regions prone to eQTL-driven differential expression, and how it can improve functional enrichment analyses through gene exclusion or weighting of gene-level rankings. Advantageously, this improved ability to identify probable eQTLs also reveals examples of CC-DEGs that are likely to be functionally related to a mutant phenotype. This supports a long-standing prediction that selection for advantageous linkage disequilibrium influences chromosome evolution. By comparing the genomes of zebrafish (Danio rerio) and medaka (Oryzias latipes), a teleost with a conserved ancestral karyotype, we find possible examples of chromosomal aggregation of CC-DEGs during evolution of the zebrafish lineage. The DAR metric provides a solid foundation for addressing the eQTL issue in new and existing datasets because it relies solely on RNA-sequencing data.

genetics↗

bioRxiv2022

Fake IDs? Widespread misannotation of DNA Transposons as a General Transcription Factor

The annotation of transposable elements (TEs) is a critical part of our understanding of genomes, however, the accuracy of annotation pipelines remains an issue as TEs are frequently underestimated or misannotated. We report the General Transcription Factor II-I Repeat Domain-Containing Protein 2 (GTF2IRD2) was used to erroneously annotate DNA transposons in a variety of non-mammalian species as GTF2IRD2 contains a 3 fused hAT transposase domain. This study emphasises that the misannotation of TEs as trans-regulatory elements, such as transcription factors, can lead to errors in phylogenetic trees based on orthologs and to significant wasted time for investigators interested in gene regulation and characterising non-mammalian genomes.

genomics↗

bioRxiv2022

Transient Polycomb activity represses developmental genes in growing oocytes.

BackgroundNon-genetic disease inheritance and offspring phenotype is substantially influenced by germline epigenetic programming, including genomic imprinting. Loss of Polycomb Repressive Complex 2 (PRC2) function in oocytes causes non-genetically inherited effects on offspring, including embryonic growth restriction followed by post-natal offspring overgrowth. While PRC2 dependent non-canonical imprinting is likely to contribute, less is known about germline epigenetic programming of non-imprinted genes during oocyte growth. In addition, de novo germline mutations in genes encoding PRC2 lead to overgrowth syndromes in human patients, but the extent to which PRC2 activity is conserved in human oocytes is poorly understood. ResultsIn this study we identify a discrete period of early oocyte growth during which PRC2 is expressed in mouse growing oocytes. Deletion of Eed during this window led to the de-repression of 343 genes. A high proportion of these were developmental regulators, and the vast majority were not imprinted genes. Many of the de-repressed genes were also marked by the PRC2-dependent epigenetic modification histone 3 lysine 27 trimethylation (H3K27me3) in primary-secondary mouse oocytes, at a time concurrent with PRC2 expression. In addition, we found H3K27me3 was also enriched on many of these genes by the germinal vesicle (GV) stage in human oocytes, strongly indicating that this PRC2 function is conserved in the human germline. However, while the 343 genes were de-repressed in mouse oocytes lacking EED, they were not de-repressed in pre-implantation embryos and lost H3K27me3 during pre-implantation development. This implies that H3K27me3 is a transient feature that represses a wide range of genes in oocytes. ConclusionsTogether, these data indicate that EED has spatially and temporally distinct functions in the female germline to repress a wide range of developmentally important genes, and that this activity is conserved in the mouse and human germlines.

developmental biology↗

bioRxiv2022

Loss of EED in the oocyte causes initial fetal growth restriction followed by placental hyperplasia and offspring overgrowth

Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to placental hyperplasia in mammalian offspring generated by somatic cell nuclear transfer (SCNT). In this study, we show that offspring from mouse oocytes lacking the Polycomb protein Embryonic Ectoderm Development (EED) were initially growth restricted, characterised by low blastocyst cell counts and substantial mid-gestational developmental delay. This initial developmental delay was followed by striking late-gestational placental hyperplasia, fetal catch-up growth and extended gestational length that culminated in offspring overgrowth. This involved remodelling of the placenta, including expansion of fetal and maternal tissues and conspicuous expansion of the glycogen enriched cell population in the junctional zone that was associated with a delay in parturition. Despite this remodelling and offspring catchup growth, fetal/placental weight ratio and fetal blood glucose levels were low indicating low placental efficiency. Genome-wide analyses identified extensive transcriptional dysregulation in affected placentas, including a range of imprinted and non-imprinted genes and increased expression of the H3K27me3-imprinted gene Slc38a4, which regulates transport of essential amino acids in the placenta. Our data provide an explanation for apparently opposing observations of growth restriction and overgrowth of offspring derived from Eed-null oocytes and demonstrate that PRC2-dependent programming in the oocyte regulates fetal and placental growth and developmental outcomes.

developmental biology↗

bioRxiv2022

Widespread of horizontal gene transfer regions in eukaryotes

Horizontal gene transfer (HGT) is the transfer of genetic material between distantly related organisms. While most genes in prokaryotes can be horizontally transferred, HGT events in eukaryotes are considered as rare, particularly in mammals. Here we reported the identification of HGT regions (HGTs), which are genomic sequence fragments indicating the occurrence of HGT events, in human, mouse, cow, lizard, frog, zebrafish, fruit fly, nematode, Arabidopsis and yeast. By comparing the genomes of these 10 representative eukaryotes with 1,496 eukaryotic genomes, 16,098 bacteria and 11,695 viruses, we found between 10 and 243 non-redundant HGTs per species, and most of these HGTs were previously unknown. These HGTs have transformed their host genomes with various numbers of copies and have impacted hundreds, even thousands of genes. We listed several examples of HGTs and proposed some possible routes that HGT events occurred. Further analysis showed that the majority of the 1,496 eukaryotes with full length genome sequences also contain HGTs. Our findings reveal that HGT is widespread in eukaryotic genomes, and HGT is a ubiquitous driver of genome evolution for eukaryotes.

genomics↗

bioRxiv2021

Horizontal transfer and southern migration: the tale of Hydrophiinae's marine journey.

Transposable elements (TEs), also known as jumping genes, are sequences able to move or copy themselves within a genome. As TEs move throughout genomes they often act as a source of genetic novelty, hence understanding TE evolution within lineages may help in understanding environmental adaptation. Studies into the TE content of lineages of mammals such as bats have uncovered horizontal transposon transfer (HTT) into these lineages, with squamates often also containing the same TEs. Despite the repeated finding of HTT into squamates, little comparative research has examined the evolution of TEs within squamates. Here we examine a diverse family of Australo-Melanesian snakes (Hydrophiinae) to examine if the previously identified, order-wide pattern of variable TE content and activity holds true on a smaller scale. Hydrophiinae diverged from Asian elapids [~]30 Mya and have since rapidly diversified into six amphibious, [~]60 marine and [~]100 terrestrial species which fill a broad range of ecological niches. We find TE diversity and expansion differs between hydrophiines and their Asian relatives and identify multiple HTTs into Hydrophiinae, including three likely transferred into the ancestral hydrophiine from fish. These HTT events provide the first tangible evidence that Hydrophiinae reached Australia from Asia via a marine route.

evolutionary biology↗

bioRxiv2021

Horizontal transfer and subsequent explosive expansion of a DNA transposon in sea kraits (Laticauda)

Transposable elements (TEs) are self replicating genetic sequences and are often described as important "drivers of evolution". This driving force is because TEs promote genomic novelty by enabling rearrangement, and through exaptation as coding and regulatory elements. However, most TE insertions will be neutral or harmful, therefore host genomes have evolved machinery to supress TE expansion. Through horizontal transposon transfer (HTT) TEs can colonise new genomes, and since new hosts may not be able to shut them down, these TEs may proliferate rapidly. Here we describe HTT of the Harbinger-Snek DNA transposon into sea kraits (Laticauda), and its subsequent explosive expansion within Laticauda genomes. This HTT occurred following the divergence of Laticauda from terrestrial Australian elapids ~15-25 Mya. This has resulted in numerous insertions into introns and regulatory regions, with some insertions into exons which appear to have altered UTRs or added sequence to coding exons. Harbinger-Snek has rapidly expanded to make up 8-12% of Laticauda spp. genomes; this is the fastest known expansion of TEs in amniotes following HTT. Genomic changes caused by this rapid expansion may have contributed to adaptation to the amphibious-marine habitat.

genomics↗

bioRxiv2021

Genome stability is in the eye of the beholder: recent retrotransposon activity varies significantly across avian diversity

Since the sequencing of the zebra finch genome it has become clear the avian genome, while largely stable in terms of chromosome number and gene synteny, is more dynamic at an intrachromosomal level. A multitude of intrachromosomal rearrangements and significant variation in transposable element content have been noted across the avian tree. Transposable elements (TEs) are a source of genome plasticity, because their high similarity enables chromosomal rearrangements through non-allelic homologous recombination, and they have potential for exaptation as regulatory and coding sequences. Previous studies have investigated the activity of the dominant TE in birds, CR1 retrotransposons, either focusing on their expansion within single orders, or comparing passerines to non-passerines. Here we comprehensively investigate and compare the activity of CR1 expansion across orders of birds, finding levels of CR1 activity vary significantly both between and with orders. We describe high levels of TE expansion in genera which have speciated in the last 10 million years including kiwis, geese and Amazon parrots; low levels of TE expansion in songbirds across their diversification, and near inactivity of TEs in the cassowary and emu for millions of years. CR1s have remained active over long periods of time across most orders of neognaths, with activity at any one time dominated by one or two families of CR1s. Our findings of higher TE activity in species-rich clades and dominant families of TEs within lineages mirror past findings in mammals. Author SummaryTransposable elements (TEs) are mobile, self replicating DNA sequences within a species genome, and are ubiquitous sources of mutation. The dominant group of TEs within birds are chicken repeat 1 (CR1) retrotransposons, making up 7-10% of the typical avian genome. Because past research has examined the recent inactivity of CR1s within model birds such as the chicken and the zebra finch, this has fostered an erroneous view that all birds have low or no TE activity on recent timescales. Our analysis of numerous high quality avian genomes across multiple orders identified both similarities and significant differences in how CR1s expanded. Our results challenge the established view that TEs in birds are largely inactive and instead suggest that their variation in recent activity may contribute to lineage-specific changes in genome structure. Many of the patterns we identify in birds have previously been seen in mammals, highlighting parallels between the evolution of birds and mammals.

evolutionary biology↗

bioRxiv2020

New environment, new invaders - repeated horizontal transfer of LINEs to sea snakes

While numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Mya. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. Such major shifts in habitat should require significant genomic changes.The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar transposons present in fish and marine invertebrates. The one exception was a similar transposon found in sea kraits, a lineage of amphibious elapids which independently transitioned to a marine environment following their divergence from terrestrial species 25 Mya. Our finding of repeated horizontal transfer events into separate lineages of marine snakes greatly expands past findings of frequent horizontal transfer in the marine environment, suggesting it is ideal for the transfer of transposons.Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. This provides evidence of the environment influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.

evolutionary biology↗

bioRxiv2019

The tuatara genome: insights into vertebrate evolutionfrom the sole survivor of an ancient reptilian order

The tuatara (Sphenodon punctatus), the only living member of the archaic reptilian order Rhynchocephalia (Sphenodontia) once widespread across Gondwana, is an iconic and enigmatic terrestrial vertebrate endemic to New Zealand. A key link to the now extinct stem reptiles from which dinosaurs, modern reptiles, birds and mammals evolved, the tuatara provides exclusive insights into the ancestral amniotes. The tuatara genome, at [~]5 Gbp, is among the largest vertebrate genomes assembled. Analysis of this genome and comparisons to other vertebrates reinforces the uniqueness of the tuatara. Phylogenetic analyses indicate tuatara diverged from the snakes and lizards [~]250 MYA. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Genome sequence analysis identifies expansions of protein, non-protein-coding RNA families, and repeat elements, the latter of which show an extraordinary amalgam of reptilian and mammalian features. Sequencing of this genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. It also provides important insights into both the technical challenges and the cultural obligations associated with genome sequencing.

genomics↗