Multiple recent sex chromosome fusions in Drosophila virilis associated with elevated satellite DNA abundance

Repetitive satellite DNA is highly variable both within and between species, and is often located near centromeres. However, the abundance or array length of satellite DNA may be constrained or have maximum limits. Drosophila virilis contains among the highest relative satellite abundances, with almost half its genome composed of three related 7 bp satellites. We discovered a strain of D. virilis that has 15% more pericentromeric satellite DNA compared to other strains, and also underwent two independent centromere-to-centromere sex chromosome fusion events. These fusions are presumably caused by DNA breakage near the pericentromeric satellites followed by repair using similar repetitive regions of nonhomologous chromosomes. We hypothesized that excess satellite DNA might increase the risk of DNA breaks and genome instability when stressed, which would be consistent with the apparent high rate of fusions we found in this strain. To directly quantify DNA breakage levels between strains with different satellite DNA abundances, we performed the comet assay after feeding flies gemcitabine and administering low-dose gamma radiation. We found a positive correlation between the rate of DNA breakage and satellite DNA abundance. This was further supported by a significant decrease in DNA breakage in an otherwise genetically identical substrain that lost the chromosome fusion and several megabases of satellite DNA. We find that the centromere-to-centromere fusions resulted in up to a 21% nondisjunction rate between the X and Y chromosomes in males, adding a fitness cost. Finally, we propose a model consistent with our data that implicates genome instability as a critical evolutionary constraint to satellite abundance.

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Radiation-Induced DNA Breaks in Different Human Satellite DNA Sequence Areas, Analyzed by DNA Breakage Detection-FluorescenceIn SituHybridization

Radiation Research ◽

10.1667/0033-7587(2002)157[0711:ridbid]2.0.co;2 ◽

2002 ◽

Vol 157 (6) ◽

pp. 711-720 ◽

Cited By ~ 9

Author(s):

Fernando Vázquez-Gundín ◽

María Teresa Rivero ◽

Jaime Gosálvez ◽

José Luis Fernández

Keyword(s):

Dna Sequence ◽

Satellite Dna ◽

Dna Breaks ◽

Dna Breakage ◽

Radiation Induced

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Sex chromosome pairing mediated by euchromatic homology in Drosophila male meiosis

10.1101/854877 ◽

2019 ◽

Author(s):

Christopher A. Hylton ◽

Katie Hansen ◽

Andrew Bourgeois ◽

John E. Tomkiel

Keyword(s):

Sex Chromosomes ◽

Sex Chromosome ◽

Intergenic Spacer ◽

Male Meiosis ◽

Early Prophase ◽

Dna Breaks ◽

Late Prophase ◽

Prophase I ◽

Y Chromosomes ◽

Meiosis I

ABSTRACTTo maintain proper ploidy, haploid sex cells must undergo two subsequent meiotic divisions. During meiosis I, homologs pair and remain conjoined until segregation at anaphase. Drosophila melanogaster spermatocytes are unique in that the canonical events of meiosis I including synaptonemal complex (SC) formation, double-strand DNA breaks, and chiasmata are absent. Sex chromosomes pair at intergenic spacer sequences within the heterochromatic rDNA while euchromatin is required to pair and segregate autosomal homologies, suggesting that pairing may be limited to specific sequences. However, previous work generated from genetic segregation assays or observations of late prophase I/prometaphase I chromosome associations fail to differentiate pairing from conjunction. Here, we separately examined the capability of X euchromatin to pair and conjoin using an rDNA-deficient X and a series of Dp(1;Y) chromosomes. Genetic assays showed that duplicated X euchromatin can substitute for endogenous rDNA pairing sites. Segregation was not proportional to homology length, and pairing could be mapped to nonoverlapping sequences within a single Dp(1;Y). Using fluorescent in situ hybridization (FISH) to early prophase I spermatocytes, we showed that pairing occurred with high fidelity at all homologies tested. Pairing was unaffected by the presence of X rDNA, nor could it be explained by rDNA magnification. By comparing genetic and cytological data, we determined that centromere proximal pairings were best at segregation. Segregation was dependent on the conjunction protein Stromalin in Meiosis while the autosomal-specific Teflon was dispensable. Overall, our results suggest that pairing may occur at all homologies, but there may be sequence or positional requirements for conjunction.ARTICLE SUMMARYDrosophila males have evolved a unique system of chromosome segregation in meiosis that lacks recombination. Chromosomes pair at selected sequences suggesting that early steps of meiosis may also differ in this organism. Using Y chromosomes carrying portions of X material, we show that pairing between sex chromosomes can be mediated by sequences other than the previously identified rDNA pairing sites. We propose that pairing may simply be homology-based and may not differ from canonical meiosis observed in females. The main difference in males may be that conjunctive mechanisms that join homologs in the absence of crossovers.

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Telomere-to-telomere assembly of a fish Y chromosome reveals the origin of a young sex chromosome pair

Genome Biology ◽

10.1186/s13059-021-02430-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lingzhan Xue ◽

Yu Gao ◽

Meiying Wu ◽

Tian Tian ◽

Haiping Fan ◽

...

Keyword(s):

Y Chromosome ◽

Sex Chromosomes ◽

Chromosome Pair ◽

Sex Chromosome ◽

Structural Variations ◽

Recombination Suppression ◽

Chromosome Differentiation ◽

Y Chromosomes ◽

Recent Origin ◽

Mastacembelus Armatus

Abstract Background The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, providing species for studying how and why recombination suppression evolved in the initial stages of sex chromosome differentiation, but this requires accurate sequence assembly of the X and Y (or Z and W) chromosomes, which may be difficult if they are recently diverged. Results Here we produce a haplotype-resolved genome assembly of zig-zag eel (Mastacembelus armatus), an aquaculture fish, at the chromosomal scale. The diploid assembly is nearly gap-free, and in most chromosomes, we resolve the centromeric and subtelomeric heterochromatic sequences. In particular, the Y chromosome, including its highly repetitive short arm, has zero gaps. Using resequencing data, we identify a ~7 Mb fully sex-linked region (SLR), spanning the sex chromosome centromere and almost entirely embedded in the pericentromeric heterochromatin. The SLRs on the X and Y chromosomes are almost identical in sequence and gene content, but both are repetitive and heterochromatic, consistent with zero or low recombination. We further identify an HMG-domain containing gene HMGN6 in the SLR as a candidate sex-determining gene that is expressed at the onset of testis development. Conclusions Our study supports the idea that preexisting regions of low recombination, such as pericentromeric regions, can give rise to SLR in the absence of structural variations between the proto-sex chromosomes.

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Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes

Genetics Research ◽

10.1017/s0016672301005109 ◽

2001 ◽

Vol 78 (1) ◽

pp. 23-30 ◽

Cited By ~ 65

Author(s):

MARIKO KONDO ◽

ERIKO NAGAO ◽

HIROSHI MITANI ◽

AKIHIRO SHIMA

Keyword(s):

Genetic Map ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Oryzias Latipes ◽

Male Recombination ◽

Male And Female ◽

Y Chromosomes ◽

Genetic Length ◽

Expressed Sequence ◽

Group 1

In the medaka, Oryzias latipes, sex is determined chromosomally. The sex chromosomes differ from those of mammals in that the X and Y chromosomes are highly homologous. Using backcross panels for linkage analysis, we mapped 21 sequence tagged site (STS) markers on the sex chromosomes (linkage group 1). The genetic map of the sex chromosome was established using male and female meioses. The genetic length of the sex chromosome was shorter in male than in female meioses. The region where male recombination is suppressed is the region close to the sex-determining gene y, while female recombination was suppressed in both the telomeric regions. The restriction in recombination does not occur uniformly on the sex chromosome, as the genetic map distances of the markers are not proportional in male and female recombination. Thus, this observation seems to support the hypothesis that the heterogeneous sex chromosomes were derived from suppression of recombination between autosomal chromosomes. In two of the markers, Yc-2 and Casp6, which were expressed sequence-tagged (EST) sites, polymorphisms of both X and Y chromosomes were detected. The alleles of the X and Y chromosomes were also detected in O. curvinotus, a species related to the medaka. These markers could be used for genotyping the sex chromosomes in the medaka and other species, and could be used in other studies on sex chromosomes.

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Fire-Setting Behavior in Individuals With Klinefelter Syndrome

PEDIATRICS ◽

10.1542/peds.82.1.115 ◽

1988 ◽

Vol 82 (1) ◽

pp. 115-117

Author(s):

MARVIN E. MILLER ◽

STEPHEN SULKES

Keyword(s):

Criminal Behavior ◽

Sex Chromosome ◽

Klinefelter Syndrome ◽

Mental Deficiency ◽

The Other ◽

Sexual Deviation ◽

Reactive Depression ◽

Y Chromosomes ◽

Psychiatric Problems ◽

Chromosome Disorder

Klinefelter syndrome is a sex chromosome disorder with an incidence of approximately two per 1,000 male newborns.1 Eighty percent of individuals with Klinefelter syndrome are 47,XXY, whereas the other 20% have a variant sex chromosomal constitution with additional supernumerary X or Y chromosomes (ie, 48,XXXY, 48XXYY) or are mosaic.2 Individuals with Klinefelter syndrome have small testes which usually cannot produce sperm or normal amounts of testosterone. The results of this are infertility and undermasculinization. Behavioral and psychiatric problems are also common in individuals with Klinefelter syndrome and include personality disorder, reactive depression, schizophrenia, mental deficiency, sexual deviation, criminal behavior, and alcoholism.3

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Repression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability

Molecular Cell ◽

10.1016/j.molcel.2018.11.001 ◽

2019 ◽

Vol 73 (2) ◽

pp. 212-223.e7 ◽

Cited By ~ 38

Author(s):

Cornelia Meisenberg ◽

Sarah I. Pinder ◽

Suzanna R. Hopkins ◽

Sarah K. Wooller ◽

Graeme Benstead-Hume ◽

...

Keyword(s):

Genome Instability ◽

Dna Breaks

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The Continuum of Psychosis and Its Genetic Origins

The British Journal of Psychiatry ◽

10.1192/bjp.156.6.788 ◽

1990 ◽

Vol 156 (6) ◽

pp. 788-797 ◽

Cited By ~ 187

Author(s):

T. J. Crow

Keyword(s):

Sex Chromosome ◽

Homo Sapiens ◽

Polymorphic Marker ◽

Cerebral Dominance ◽

Homo Erectus ◽

Evolutionary Development ◽

Pseudoautosomal Region ◽

Sibling Pairs ◽

Homo Habilis ◽

Y Chromosomes

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A post-mortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggests that the gene for psychosis is the ‘cerebral dominance gene‘, the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition fromAustralopithecusthroughHomo habilisandHomo erectustoHomo sapiens.

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Analysis of BAC clones containing homologous sequences on the end of the Xq arm and on chromosome 7 in the dioecious plant Silene latifolia

Genome ◽

10.1139/g10-008 ◽

2010 ◽

Vol 53 (4) ◽

pp. 311-320 ◽

Cited By ~ 4

Author(s):

Kotaro Ishii ◽

Yasuhito Amanai ◽

Yusuke Kazama ◽

Miho Ikeda ◽

Hiroshi Kamada ◽

...

Keyword(s):

Satellite Dna ◽

Sex Chromosome ◽

Artificial Chromosome ◽

Chromosome 7 ◽

Silene Latifolia ◽

Dioecious Plant ◽

Homologous Sequences ◽

Autosomal Region ◽

Single Primer

Silene latifolia is a model dioecious plant with morphologically distinguishable XY sex chromosomes. The end of the Xq arm is quite different from that of the Yp arm, although both are located at opposite ends of their respective chromosomes relative to a pseudo-autosomal region. The Xq arm does not seem to originate from the same autosome as the Yp arm. Bacterial artificial chromosome clone #15B12 has an insert containing a 130-kb stretch in which a 313-bp satellite DNA is repeated 420 times. PCR with a single primer revealed that this 130-kb stretch consists of three reversals of the orientation of the satellite DNA. A non-long terminal repeat retroelement and two sequences that share homology with an Oryza sativa RING zinc finger and a putative Arabidopsis thaliana protein, respectively, were found in the sequences that flank the satellite DNA. Fluorescence in situ hybridization carried out using this low-copy region of #15B12 as a probe confirmed that these sequences originated from the X chromosome and that homologous sequences exist at the end of chromosome 7. The region distal to DD44X on the Xq arm is postulated to have recombined with a region containing satellite DNA on chromosome 7 during the process of sex chromosome evolution.

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TDP-43 mutations link Amyotrophic Lateral Sclerosis with R-loop homeostasis and R loop-mediated DNA damage

PLoS Genetics ◽

10.1371/journal.pgen.1009260 ◽

2020 ◽

Vol 16 (12) ◽

pp. e1009260

Author(s):

Marta Giannini ◽

Aleix Bayona-Feliu ◽

Daisy Sproviero ◽

Sonia I. Barroso ◽

Cristina Cereda ◽

...

Keyword(s):

Dna Damage ◽

Amyotrophic Lateral Sclerosis ◽

Rna Binding ◽

Neurodegenerative Disorder ◽

Genome Instability ◽

Neuronal Model ◽

Dna Breaks ◽

Dna And Rna ◽

Double Strand Dna Breaks ◽

Lateral Sclerosis

TDP-43 is a DNA and RNA binding protein involved in RNA processing and with structural resemblance to heterogeneous ribonucleoproteins (hnRNPs), whose depletion sensitizes neurons to double strand DNA breaks (DSBs). Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, in which 97% of patients are familial and sporadic cases associated with TDP-43 proteinopathies and conditions clearing TDP-43 from the nucleus, but we know little about the molecular basis of the disease. After showing with the non-neuronal model of HeLa cells that TDP-43 depletion increases R loops and associated genome instability, we prove that mislocalization of mutated TDP-43 (A382T) in transfected neuronal SH-SY5Y and lymphoblastoid cell lines (LCLs) from an ALS patient cause R-loop accumulation, R loop-dependent increased DSBs and Fanconi Anemia repair centers. These results uncover a new role of TDP-43 in the control of co-transcriptional R loops and the maintenance of genome integrity by preventing harmful R-loop accumulation. Our findings thus link TDP-43 pathology to increased R loops and R loop-mediated DNA damage opening the possibility that R-loop modulation in TDP-43-defective cells might help develop ALS therapies.

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Rad51 and Mitotic Function of Mus81 are Essential for Recovery from Low-Dose of Camptothecin in the Absence of the Wrn Exonuclease

10.1101/399881 ◽

2018 ◽

Author(s):

Francesca Antonella Aiello ◽

Anita Palma ◽

Eva Malacaria ◽

Li Zheng ◽

Judith L. Campbell ◽

...

Keyword(s):

Cell Death ◽

Topoisomerase I ◽

Genome Instability ◽

Alternative Mechanism ◽

Exonuclease Activity ◽

Replication Forks ◽

Wild Type ◽

Dna Breaks ◽

Alternative Processing ◽

Mitotic Abnormalities

ABSTRACTStabilisation of the stalled replication fork is crucial to prevent excessive fork reversal or degradation, which can undermine genome integrity. The WRN protein is a human RecQ helicase that participates in the processing and recovery of perturbed replication forks. WRN is unique among the other human RecQ family members to possess exonuclease activity. However, the biological role of the WRN exonuclease is poorly defined, and little is known about an involvement in the response to perturbed replication. Recently, the WRN exonuclease has been linked to protection of stalled forks from MRE11-dependent degradation in response to clinically-relevant nanomolar doses of the Topoisomerase I inhibitor camptothecin. Alternative processing of perturbed forks has been associated to chemoresistance of BRCA-deficient cancer cells, thus, we used WRN exonuclease-deficiency as a model to investigate the fate of perturbed replication forks undergoing degradation, but in a BRCA wild-type condition. We find that, upon nanomolar doses of camptothecin, loss of WRN exonuclease stimulates fork inactivation and accumulation of parental gaps, which engages RAD51. Such alternative mechanism affects reinforcement of CHK1 phosphorylation and causes persistence of RAD51 during recovery from treatment. Notably, in WRN exonuclease-deficient cells, persistence of RAD51 correlates with elevated mitotic phosphorylation of MUS81 at Serine 87, which is essential to avoid accumulation of mitotic abnormalities. Altogether, these findings indicate that aberrant fork degradation, in the presence of a wild-type RAD51 axis, stimulates RAD51-mediated post-replicative repair and engagement of the MUS81 complex to limit genome instability and cell death.AUTHOR SUMMARYCorrect progression of the molecular machine copying the chromosomes is threatened by multiple causes that induce its delay or arrest. Once the replication machinery is arrested, the cell needs to stabilise it to prevent DNA damage. Many proteins contribute to this task and the Werner’s syndrome protein, WRN, is one of them.Defining what happens to replication machineries when they are blocked is highly relevant. Indeed, destabilised replication machineries may form upon treatment with anticancer drugs and influence the efficacy of some of them in specific genetic backgrounds. We used cells that lack one of the two enzymatic functions of WRN, the exonuclease activity, to investigate the fate of destabilised replication machineries. Our data show that they are handled by a repair pathway normally involved in fixing DNA breaks but, in this case, recruited to deal with regions of the genome that are left unreplicated after their destabilisation. This alternative mechanism involves a protein, RAD51, which tries to copy DNA from the sister chromosome. In so doing, however, RAD51 produces a lot of DNA interlinking that requires upregulation of a complex, called MUS81/EME1, which resolves this interlinking prior cell division and prevents accumulation of mitotic defects and cell death.

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