Chromosome Structure Research Articles

PICH, A protein that maintains genomic stability, can promote tumor growth.

Genomic instability is regardedas a hallmark of cancer cells. It can be presented in many ways, among which chromosome instability has received attention. Ultrafine anaphase bridges are a typeof chromatin bridges, the untimely resolution of which can also lead to chromosome instability. PICH can play a role in maintaining chromosome stability by regulating chromosome morphologyand resolving ultrafine anaphase bridges. Recently, PICH has been found to be overexpressed in various cancers. Overexpression of PICH is related to the proliferation of tumors and poor prognosis. In this article, we consider that PICH can maintain genome stability by regulating appropriate chromosome structure, ensuring proper chromosome segregation, and facilitating replication fork reversal. We summarize how PICH regulates chromosome stability, how PICH resolves Ultrafine anaphase bridges with other proteins, and how PICH promotes tumor progression.

Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps.

Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis Short-read genome sequencing (srGS) can only resolve ∼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases.

Comparative linkage mapping to investigate synteny and recombination in social Vespidae

Abstract Genetic linkage maps are valuable resources for investigating chromosomal structure, quantifying karyotype, estimating recombination rates, and improving preexisting genome assemblies. Comparative linkage mapping, in turn, broadens our understanding of the phylogenetic history of these genomic features. Through an assessment of synteny (the conservation of gene order on homologous chromosomes in different species) and variation in recombination rate, we can begin to understand how genomic features change during the evolution of distinct species. Here, we construct high-density genetic linkage maps for 3 Vespidae wasp species from the Vespula genus: Vespula consobrina, Vespula pensylvanica, and Vespula vidua to investigate shared genomic architecture between these 3 yellowjacket wasp species. We show that these species exhibit high levels of collinearity, often in chromosome-length blocks of synteny, with some evidence for small interchromosomal rearrangements. We also identify 2 “inversions” in all 3 species that are likely artifacts from the genome assembly process. In addition, we map genome-wide recombination rates and reveal the recombination landscape to be highly variable on intrachromosomal, interchromosomal, and interspecific scales. Genome-wide recombination rates are high for all three Vespula species, (V. pensylvanica: 22.7 cM/Mb, V. consobrina: 24.3 cM/Mb, and V. vidua: 24.7 cM/Mb), which is consistent with findings of high recombination rates for other eusocial species. Our high-quality linkage maps will be resources for ongoing evolutionary genetics studies interested in the genome evolution of social wasps.

Carcinogenic Mechanisms of Hexavalent Chromium: From DNA Breaks to Chromosome Instability and Neoplastic Transformation.

Hexavalent chromium [Cr(VI)] is a well-established human carcinogen, yet the mechanisms by which it leads to carcinogenic outcomes is still unclear. As a driving factor in its carcinogenic mechanism, Cr(VI) causes DNA double strand breaks and break-repair deficiency, leading to the development of chromosome instability. Therefore, the aim of this review is to discuss studies assessing Cr(VI)-induced DNA double strand breaks, chromosome damage and instability, and neoplastic transformation including cell culture, experimental animal, human pathology and epidemiology studies. Recent findings confirm Cr(VI) induces DNA double strand breaks, chromosome instability and neoplastic transformation in exposed cells, animals and humans, emphasizing these outcomes as key steps in the mechanism of Cr(VI) carcinogenesis. Moreover, recent findings suggest chromosome instability is a key phenotype in Cr(VI)-neoplastically transformed clones and is an inheritable and persistent phenotype in exposed cells, once more suggesting chromosome instability as central in the carcinogenic mechanism. Although limited, some studies have demonstrated DNA damage and epigenetic modulation are also key outcomes in biopsies from chromate workers that developed lung cancer. Additionally, we also summarized new studies showing Cr(VI) causes genotoxic and clastogenic effects in cells from wildlife, such as sea turtles, whales, and alligators. Overall, across the literature, it is clear that Cr(VI) causes neoplastic transformation and lung cancer. Many studies measured Cr(VI)-induced increases in DNA double strand breaks, the most lethal type of breaks clearly showing that Cr(VI) is genotoxic. Unrepaired or inaccurately repaired breaks lead to the development of chromosome instability, which is a common phenotype in Cr(VI) exposed cells, animals, and humans. Indeed, many studies show Cr(VI) induces both structural and numerical chromosome instability. Overall, the large body of literature strongly supports the conclusion that Cr(VI) causes DNA double strand breaks, inhibits DNA repair and chromosome instability, which are key to the development of Cr(VI)-induced cell transformation.

Insertion sequence elements and unique symmetrical genomic regions mediate chromosomal inversions in Streptococcus pyogenes.

Chromosomal inversions are a phenomenon in many bacterial species, often across the axis of replication. Inversions have been shown to alter gene expression, changing persistence of colonisation and infection following environmental stresses. In Streptococcus pyogenes, inversions have been reported. However, frequency and molecular markers of inversions have not been systematically examined. Here, 249 complete S.pyogenes genomes were analysed using a pangenomic core gene synteny framework to identify sequences associated with inversions. 47% of genomes (118/249) contained at least one inversion, from 23 unique inversion locations. Chromosomal locations enabling inversions were usually associated with mobile elements (insertion sequences n=9 and prophages n=7). Two insertion sequences, IS1548 and IS1239, accounted for>80% of insertion sequences and were the only insertion sequences associated with inversions. The most observed inversion location (n=104 genomes, 88% of genomes with an inversion) occurs between two conserved regions encoding rRNAs, tRNAsand sigma factor genes. The regions are symmetrically placed around the origin of replication forming a unique chromosomal structure inS. pyogenes, relative to other streptococci. Cataloging of thechromosomal location and frequency of inversions can direct dissection of phenotypic changes following chromosomal inversions. The framework used here can be transferred to other bacterial species to characterise chromosomal inversions.

Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew.

Plant pathogens adapt at speeds that challenge contemporary disease management strategies like the deployment of disease resistance genes. The strong evolutionary pressure to adapt, shapes pathogens' genomes, and comparative genomics has been instrumental in characterizing this process. With the aim to capture genomic variation at high resolution and study the processes contributing to adaptation, we here leverage an innovative, multi-genome method to construct and annotate the first pangenome graph of an oomycete plant pathogen. We expand on this approach by analysing the graph and creating synteny based single-copy orthogroups for all genes. We generated telomere-to-telomere genome assemblies of six genetically diverse isolates of the oomycete pathogen Peronospora effusa, the economically most important disease in cultivated spinach worldwide. The pangenome graph demonstrates that P. effusa genomes are highly conserved, both in chromosomal structure and gene content, and revealed the continued activity of transposable elements which are directly responsible for 80% of the observed variation between the isolates. While most genes are generally conserved, virulence related genes are highly variable between the isolates. Most of the variation is found in large gene clusters resulting from extensive copy-number expansion. Pangenome graph-based discovery can thus be effectively used to capture genomic variation at exceptional resolution, thereby providing a framework to study the biology and evolution of plant pathogens.

Development of a novel computational technique to create DNA and cell geometrical models for Geant4-DNA

BackgroundThis study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve. MethodsA Python-based tool named “complexDNA” was developed to facilitate the design of both simple and complex DNA geometries. This tool was employed to construct a human cell geometry with individual pairs of chromosomes. Subsequently, the performance of this chromosomal model was compared to the standard human cell model provided in the “molecularDNA” Geant4-DNA example. ResultsSimulations using the new chromosomal model revealed minimal discrepancies in DNA damage yield and fragment size distribution compared to the default human cell model. Notably, the chromosomal model demonstrated significant computational efficiency, requiring approximately three times less simulation time to achieve equivalent results. ConclusionsThis work highlights the importance of incorporating chromosomal structure into human cell models for radiation biology research. The “complexDNA” tool offers a valuable resource for creating intricate DNA structures for future studies. Further refinements, such as implementing smaller voxels for euchromatin regions, are proposed to enhance the model’s accuracy.

In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Chromosome Structural Rearrangements in Invasive Haplodiploid Ambrosia Beetles Revealed by the Genomes of Euwallacea fornicatus (Eichhoff) and Euwallacea similis (Ferrari) (Coleoptera, Curculionidae, Scolytinae).

Bark and ambrosia beetles are among the most ecologically and economically damaging introduced plant pests worldwide. Life history traits including polyphagy, haplodiploidy, inbreeding polygyny, and symbiosis with fungi contribute to their dispersal and impact. Species vary in their interactions with host trees, with many attacking stressed or recently dead trees, such as the globally distributed Euwallacea similis (Ferrari). Other species, like the Polyphagous Shot Hole Borer Euwallacea fornicatus (Eichhoff), can attack over 680 host plants and is causing considerable economic damage in several countries. Despite their notoriety, publicly accessible genomic resources for Euwallacea Hopkins species are scarce, hampering our understanding of their invasive capabilities as well as modern control measures, surveillance, and management. Using a combination of long and short read sequencing platforms, we assembled and annotated high quality (BUSCO > 98% complete) pseudo-chromosome-level genomes for these species. Comparative macrosynteny analysis identified an increased number of pseudo-chromosome scaffolds in the haplodiploid inbreeding species of Euwallacea compared to diploid outbred species, due to fission events. This suggests that life history traits can impact chromosome structure. Further, the genome of E. fornicatus had a higher relative proportion of repetitive elements, up to 17% more, than E. similis. Metagenomic assembly pipelines identified microbiota associated with both species including Fusarium fungal symbionts and a novel Wolbachia strain. These novel genomes of haplodiploid inbreeding species will contribute to the understanding of how life history traits are related to their evolution and to the management of these invasive pests.

Genome-Wide Identification of the Maize Chitinase Gene Family and Analysis of Its Response to Biotic and Abiotic Stresses

Background/Objectives: Chitinases, enzymes belonging to the glycoside hydrolase family, play a crucial role in plant growth and stress response by hydrolyzing chitin, a natural polymer found in fungal cell walls. This study aimed to identify and analyze the maize chitinase gene family, assessing their response to various biotic and abiotic stresses to understand their potential role in plant defense mechanisms and stress tolerance. Methods: We employed bioinformatics tools to identify 43 chitinase genes in the maize B73_V5 genome. These genes were characterized for their chromosomal positions, gene and protein structures, phylogenetic relationships, functional enrichment, and collinearity. Based on previous RNA-seq data, the analysis assessed the expression patterns of these genes at different developmental stages and under multiple stress conditions. Results: The identified chitinase genes were unevenly distributed across maize chromosomes with a history of tandem duplications contributing to their divergence. The ZmChi protein family was predominantly hydrophilic and localized mainly in chloroplasts. Expression analysis revealed that certain chitinase genes were highly expressed at specific developmental stages and in response to various stresses, with ZmChi31 showing significant responsiveness to 11 different abiotic and biotic stresses. Conclusions: This study provides new insights into the role of chitinase genes in maize stress response, establishing a theoretical framework for exploring the molecular basis of maize stress tolerance. The identification of stress-responsive chitinase genes, particularly ZmChi31, offers potential candidates for further study in enhancing maize resistance to environmental challenges.

Helical coiled nucleosome chromosome architectures during cell cycle progression

Recent studies showed an interphase chromosome architecture-a specific coiled nucleosome structure-derived from cryopreserved EM tomograms, and dispersed throughout the nucleus. The images were computationally processed to fill in the missing wedges of data caused by incomplete tomographic tilts. The resulting structures increased z-resolution enabling an extension of the proposed architecture to that of mitotic chromosomes. Here, we provide additional insights into the chromosome architecture that was recently published [M. Elbaum et al., Proc. Natl. Acad. Sci. U.S.A. 119, e2119101119 (2022)]. We build on the defined chromosomes time-dependent structures in an effort to probe their dynamics. Variants of the coiled chromosome structures, possibly further defining specific regions, are discussed. We propose, based on generalized specific uncoiling of mitotic chromosomes in telophase, large-scale reorganization of interphase chromosomes. Chromosome territories, organized as micron-sized small patches, are constructed, satisfying complex volume considerations. Finally, we unveiled the structures of replicated coiled chromosomes, still attached to centromeres, as part of chromosome architecture.

Effects of the auxin-dependent degradation of the cohesin and condensin complexes on the repair of distant DNA double-strand breaks in mouse embryonic stem cells.

The SMC protein family, including cohesin and condensin I/II, plays a pivotal role in maintaining the topological structure of chromosomes and influences many cellular processes, notably the repair of double-stranded DNA breaks (DSBs). The cohesin complex impacts DSB repair by spreading γH2AX signal and containing DNA ends in close proximity by loop extrusion. Cohesin supports DNA stability by sister chromatid cohesion during the S/G2 phase, which limits DNA end mobility. Cohesin knockdown was recently shown to stimulate frequencies of genomic deletions produced by distant paired DSBs, but does not affect DNA repair of a single or close DSBs. We examined how auxin-inducible protein degradation of Rad21 (cohesin) or Smc2 (condensins I+II) changes the frequencies of rearrangements between paired distant DSBs in mouse embryonic stem cells (mESCs). We used Cas9 RNP nucleofection to generate deletions and inversions with high efficiency without additional selection. We determined optimal Neon settings and deletion appearance timings. Two strategies for auxin addition were tested (4 independent experiments in total). We examined deletion/inversion frequencies for two regions spanning 3.5 and 3.9 kbp in size. Contrary to expectations, in our setting, Rad21 depletion did not increase deletion/inversion frequencies, not even for the region with an active Ctcf boundary. We actually observed a 12 % decrease in deletions (but not inversions). At the same time, double condensin depletion (Smc2 degron line) demonstrated high biological variability between experiments, complicating the analysis, and requires additional examination in the future. TIDE analysis revealed that editing frequency was consistent (30-50 %) for most experiments with a minor decrease after auxin addition. In the end, we discuss the Neon/ddPCR method for deletion generation and detection in mESCs.

Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.

The rise of induced pluripotent stem cells (iPSCs) technology has ushered in a landmark shift in the study of hereditary diseases. However, there is a scarcity of reports that offer a comprehensive and objective overview of the current state of research at the intersection of iPSCs and hereditary diseases. Therefore, this study endeavors to categorize and synthesize the publications in this field over the past decade through bibliometric methods and visual knowledge mapping, aiming to visually analyze their research focus and clinical trends. The English language literature on iPSCs and hereditary diseases, published from 2014 to 2023 in the Web of Science Core Collection (WoSCC), was examined. The CiteSpace (version 6.3.R1) software was utilized to visualize and analyze country/region, institution, scholar, co-cited authors, and co-cited journals. Additionally, the co-occurrence, clustering, and bursting of co-cited references were displayed. Analysis of 347 articles that met the inclusion criteria revealed a steady increase in the number of published articles and citation frequency in the field over the past decade. With regard to the countries/regions, institutions, scholars, and journals where the articles were published, the highest numbers were found in the USA, the University of California System, Suren M. Zakian, and Stem Cell Research, respectively. The current research is focused on the construction of disease models, both before and after correction, as well as drug target testing for single-gene hereditary diseases. Chromosome transplantation genomic therapy for hereditary diseases with abnormal chromosome structures may emerge as a future research hotspot in this field.

Systematic analysis of the ARF gene family in Fagopyrum dibotrys and its potential roles in stress tolerance.

The auxin response factor (ARF) is a plant-specific transcription factor that regulates the expression of auxin response genes by binding directly to their promoters. They play an important role in the regulation of plant growth and development, as well as in the response to biotic and abiotic stresses. However, the identification and functional analysis of ARFs in Fagopyrum dibotrys are still unclear. In this study, a total of 26 FdARF genes were identified using bioinformatic methods. Their chromosomal location, gene structure, physical and chemical properties of their encoded protein, subcellular location, phylogenetic tree, conserved motifs and cis-acting elements in FdARF promoters were analyzed. The results showed that 26 FdARF genes were unevenly distributed on 8 chromosomes, with the largest distribution on chromosome 4 and the least distribution on chromosome 3. Most FdARF proteins are located in the nucleus, except for the proteins FdARF7 and FdARF21 located to the cytoplasm and nucleus, while FdARF14, FdARF16, and FdARF25 proteins are located outside the chloroplast and nucleus. According to phylogenetic analysis, 26 FdARF genes were divided into 6 subgroups. Duplication analysis indicates that the expansion of the FdARF gene family was derived from segmental duplication rather than tandem duplication. The prediction based on cis-elements of the promoter showed that 26 FdARF genes were rich in multiple stress response elements, suggesting that FdARFs may be involved in the response to abiotic stress. Expression profiling analysis showed that most of the FdARF genes were expressed in the roots, stems, leaves, and tubers of F. dibotrys, but their expression exhibits a certain degree of tissue specificity. qRT-PCR analysis revealed that most members of the FdARF gene were up- or down-regulated in response to abiotic stress. The results of this study expand our understanding of the functional role of FdARFs in response to abiotic stress and lay a theoretical foundation for further exploration of other functions of FdARF genes.

Genome-wide investigation and analysis of U-box E3 ubiquitin-protein ligase gene family in kiwifruit (Actinidia chinensis) in response to the yeast antagonist, Wickerhamomyces anomalus

ABSTRACT Although the ubiquitin ligase U-box protein family is a vital component of plant development and stress response, the exact role of kiwifruit U-box genes family is not known. The study identified 73 putative U-box genes from the kiwifruit genome. Chromosomal localisation, phylogenetic analysis, physicochemical properties, gene structure, motifs, and promoters of these genes were analysed. Distribution of Actinidia chinensis PUB (AcPUB) genes exhibited varying densities across 27 chromosomes. The study found that U-box clusters were classified into groups I–VII in phylogenetic analyses of a variety of plants, including kiwifruit, Arabidopsis thaliana, and rice, with most of the genes in kiwifruit being related to rice. The conserved motif analyses revealed that all the AcPUB genes have typical U-box structural domains. Analysis of the cis-acting elements suggested that AcPUBs expression may be responsive to several hormones and stresses. RNA-Seq analysis showed that six kiwifruit U-box genes were differentially expressed after induction by Wickerhamomyces anomalus, suggesting a potential involvement of these U-box genes in the kiwifruit's response to W. anomalus, which might include mechanisms related to resistance. Overall, our findings provide valuable insights into the function and structure of U-box genes that will help develop new genomic technologies and study plant resistance.

How to write an ending: Telomere replication as a multistep process

Telomeres are protective nucleoprotein caps found at the natural ends of eukaryotic chromosomes and are crucial for the preservation of stable chromosomal structure. In cycling cells, telomeres are maintained by a multi-step process called telomere replication, which involves the eukaryotic replisome navigating a complex repetitive template tightly bound by specific proteins, before terminating at the chromosome end prior to a 5’ resection step that generates a protective 3’ overhang. In this review, we examine mechanistic aspects of the telomere replication process and consider how individual parts of this multistep event are integrated and coordinated with one-another.

Extrachromosomal DNA : New Players in Oncology

DNA that is found outside the main chromosomes in a cell's nucleus is known as extrachromosomal DNA. This type of DNA is not part of the standard 23 pairs of chromosomes in humans and instead exists as standalone circular or linear DNA structures. Unlike bacterial plasmids, extrachromosomal DNA in human cells contains important genetic material and holds particular significance in cancer cells. Critical characteristics of ecDNA in Cancer is that they frequently harbour amplified versions of oncogenes such as MYC, EGFR, and CCND1. These oncogenes propel the growth and survival of tumors. Cancer cells utilize ecDNA to generate multiple copies of these oncogenes, amplifying their expression without requiring alterations to the chromosomal structure. This amplification grants the cancer cells a competitive edge in growth. ecDNA plays a crucial role in the advancement and growth of cancer, as it amplifies oncogenes, genetic diversity, and resistance to treatments. Its adaptable and ever-changing characteristics empower cancer cells to adjust to external influences such as medication. Gaining insights into ecDNA's operations and impacts could lead to new possibilities for diagnosing and treating cancer, as well as developing therapies aimed at this distinct DNA structure.

2024: A "nucleoid space" odyssey featuring H-NS.

The three-dimensional architecture of the bacterial chromosome is intertwined with genome processes such as transcription and replication. Conspicuously so, that the structure of the chromosome permits accurate prediction of active genome processes. Although appreciation of this interplay has developed rapidly in the past two decades, our understanding of this subject is still in its infancy, with research primarily focusing on how the process of transcription regulates and is regulated by chromosome structure. Here, we summarize the latest developments in the field with a focus on the interplay between chromosome structure and transcription in Escherichia coli (E. coli) as mediated by H-NS-a model nucleoid structuring protein. We describe how the organization of chromosomes at the global and local scales is dependent on transcription, and how transcription is regulated by chromosome structure. Finally, we take note of studies that highlight our limited knowledge of structure-function relationships in the chromosome, and we point out research tracks that will improve our insight in the topic.

The formation and propagation of human Robertsonian chromosomes.

Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level paves the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.

Probing visual literacy skills reveals student conceptions of scale and abstraction with respect to chromosomes.

Molecular biology can be difficult for undergraduate students because course content is often taught using highly-abstract visual representations. Genetic concepts can be depicted with lines, letters, shapes, and symbols, and students need to engage their visual literacy skills to appropriately decipher these abstract representations. We previously found that undergraduate course materials almost always represent chromosomes in abstract forms, such as "X" shapes or straight lines with a dot for the centromere. We hypothesized that students struggle to apply their visual literacy skills to accurately interpret these abstract representations of chromosomes, which may be related to the frequently-documented incomplete or incorrect ideas students have about chromosome structure and function. To explore students' visual literacy related to representations of chromosomes, we conducted 35 semi-structured interviews with students who had taken at least a year of biology courses. We asked them to sketch chromosomes, interpret an abstract representation of chromosomes, and use the abstract representation to answer a question about meiosis. We found that 97% of participants (34 of 35) held conceptual errors related to chromosome structure and function. These conceptual errors were often not evident in participants' verbal definitions of chromosomes and were only revealed in their sketches or explanations of their sketches. We found that participants frequently misinterpreted X-shaped representations of chromosomes, mistook unreplicated homologous chromosomes as separated sister chromatids, and held misconceptions related to the structure and function of centromeres. These findings have implications for how chromosomes are taught in biology courses. We recommend that instructors explicitly discuss the conventions and norms of representing chromosomes as a pathway for increasing students' visual literacy in molecular biology.