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G3 (Bethesda, Md.) May 2022Salmon lice have plagued the salmon farming industry and have negatively impacted salmon populations in the wild. In response, researchers have generated high density...
Salmon lice have plagued the salmon farming industry and have negatively impacted salmon populations in the wild. In response, researchers have generated high density genetic maps, genome assemblies, transcriptomes, and whole-genome resequencing data to better understand this parasite. In this study, we used long-read sequencing technology to update the previous genome assemblies of Atlantic Ocean salmon lice with a more contiguous assembly and a more comprehensive gene catalog of Pacific Ocean salmon lice. We were also able to further characterize genomic features previously identified from other studies by using published resequenced genomes of 25 Atlantic and 15 Pacific salmon lice. One example was further characterizing the ZW sex chromosomes. For both the Atlantic and Pacific Ocean salmon lice subspecies, we found that the female W-chromosome is only a small fraction of the Z-chromosome and that the vast majority of the W and Z-chromosome do not contain conserved regions (i.e. pseudoautosomal regions). However, conserved orthologous protein sequences can still be identified between the W- and Z-chromosomes.
Topics: Animals; Copepoda; Female; Fish Diseases; Pacific Ocean; Salmo salar; Salmon; Sequence Analysis, DNA; Transcriptome
PubMed: 35404448
DOI: 10.1093/g3journal/jkac087 -
Genetics Mar 2017The production of haploid gametes during meiosis is dependent on the homology-driven processes of pairing, synapsis, and recombination. On the mammalian heterogametic...
The production of haploid gametes during meiosis is dependent on the homology-driven processes of pairing, synapsis, and recombination. On the mammalian heterogametic sex chromosomes, these key meiotic activities are confined to the pseudoautosomal region (PAR), a short region of near-perfect sequence homology between the and chromosomes. Despite its established importance for meiosis, the PAR is rapidly evolving, raising the question of how proper / segregation is buffered against the accumulation of homology-disrupting mutations. Here, I investigate the interplay of PAR evolution and function in two interfertile house mouse subspecies characterized by structurally divergent PARs, and Using cytogenetic methods to visualize the sex chromosomes at meiosis, I show that intersubspecific F hybrids harbor an increased frequency of pachytene spermatocytes with unsynapsed sex chromosomes. This high rate of asynapsis is due, in part, to the premature release of synaptic associations prior to completion of prophase I. Further, I show that when sex chromosomes do synapse in intersubspecific hybrids, recombination is reduced across the paired region. Together, these meiotic defects afflict ∼50% of spermatocytes from F hybrids and lead to increased apoptosis in meiotically dividing cells. Despite flagrant disruption of the meiotic program, a subset of spermatocytes complete meiosis and intersubspecific F males remain fertile. These findings cast light on the meiotic constraints that shape sex chromosome evolution and offer initial clues to resolve the paradox raised by the rapid evolution of this functionally significant locus.
Topics: Animals; Evolution, Molecular; Female; Male; Meiosis; Mice; Pseudoautosomal Regions
PubMed: 28100589
DOI: 10.1534/genetics.116.189092 -
Chromosome Research : An International... Dec 2022Double-strand break repair during meiosis is normally achieved using the homologous chromosome as a repair template. Heteromorphic sex chromosomes share little sequence...
Double-strand break repair during meiosis is normally achieved using the homologous chromosome as a repair template. Heteromorphic sex chromosomes share little sequence homology, presenting unique challenges to the repair of double-strand breaks. Our understanding of how heteromorphic sex chromosomes behave during meiosis has been focused on ancient sex chromosomes, where the X and Y differ markedly in overall structure and gene content. It remains unclear how more recently evolved sex chromosomes that share considerably more sequence homology with one another pair and form double-strand breaks. One possibility is barriers to pairing evolve rapidly. Alternatively, recently evolved sex chromosomes may exhibit pairing and double-strand break repair that more closely resembles that of their autosomal ancestors. Here, we use the recently evolved X and Y chromosomes of the threespine stickleback fish (Gasterosteus aculeatus) to study patterns of pairing and double-stranded break formation using molecular cytogenetics. We found that the sex chromosomes of threespine stickleback fish did not pair exclusively in the pseudoautosomal region. Instead, the chromosomes fully paired in a non-homologous fashion. To achieve this, the X chromosome underwent synaptic adjustment during pachytene to match the axis length of the Y chromosome. Double-strand break formation and repair rate also matched that of the autosomes. Our results highlight that recently evolved sex chromosomes exhibit meiotic behavior that is reminiscent of autosomes and argues for further work to identify the homologous templates that are used to repair double-strand breaks on the X and Y chromosomes.
Topics: Animals; DNA Breaks, Double-Stranded; Sex Chromosomes; DNA Repair; Meiosis; Smegmamorpha
PubMed: 35635635
DOI: 10.1007/s10577-022-09699-0 -
Molecular Cell Jun 2019Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a...
Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures-stochastic on autosomes, nearly absolute on X and Y-cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation.
Topics: Animals; Cell Cycle Proteins; Chromosome Pairing; Chromosome Segregation; Chromosomes; Crystallography, X-Ray; DNA Breaks, Double-Stranded; Female; Homologous Recombination; Male; Meiosis; Mice; Protein Conformation; Recombinases; Spermatocytes
PubMed: 31003867
DOI: 10.1016/j.molcel.2019.03.023 -
Genetics Sep 2018In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven...
In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles () to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (), never (), and occasionally synapse () at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles.
Topics: Animals; Arvicolinae; Chromosome Segregation; Genomics; Meiosis; North America; Pseudoautosomal Regions; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Sex Chromosomes; Telomere; Telomere-Binding Proteins; X Chromosome; Y Chromosome
PubMed: 30002081
DOI: 10.1534/genetics.118.301182 -
Cellular and Molecular Life Sciences :... Mar 2023In mammals, meiotic recombination is initiated by the introduction of DNA double strand breaks (DSBs) into narrow segments of the genome, defined as hotspots, which is...
In mammals, meiotic recombination is initiated by the introduction of DNA double strand breaks (DSBs) into narrow segments of the genome, defined as hotspots, which is carried out by the SPO11/TOPOVIBL complex. A major player in the specification of hotspots is PRDM9, a histone methyltransferase that, following sequence-specific DNA binding, generates trimethylation on lysine 4 (H3K4me3) and lysine 36 (H3K36me3) of histone H3, thus defining the hotspots. PRDM9 activity is key to successful meiosis, since in its absence DSBs are redirected to functional sites and synapsis between homologous chromosomes fails. One protein factor recently implicated in guiding PRDM9 activity at hotspots is EWS, a member of the FET family of proteins that also includes TAF15 and FUS/TLS. Here, we demonstrate that FUS/TLS partially colocalizes with PRDM9 on the meiotic chromosome axes, marked by the synaptonemal complex component SYCP3, and physically interacts with PRDM9. Furthermore, we show that FUS/TLS also interacts with REC114, one of the axis-bound SPO11-auxiliary factors essential for DSB formation. This finding suggests that FUS/TLS is a component of the protein complex that promotes the initiation of meiotic recombination. Accordingly, we document that FUS/TLS coimmunoprecipitates with SPO11 in vitro and in vivo. The interaction occurs with both SPO11β and SPO11α splice isoforms, which are believed to play distinct functions in the formation of DSBs in autosomes and male sex chromosomes, respectively. Finally, using chromatin immunoprecipitation experiments, we show that FUS/TLS is localized at H3K4me3-marked hotspots in autosomes and in the pseudo-autosomal region, the site of genetic exchange between the XY chromosomes.
Topics: Animals; Male; Lysine; RNA-Binding Protein FUS; Histone-Lysine N-Methyltransferase; Homologous Recombination; DNA; Meiosis; Mammals
PubMed: 36967403
DOI: 10.1007/s00018-023-04744-5 -
Nature Communications Nov 2014The molecular characteristics of the pseudoautosomal region (PAR) of sex chromosomes remain elusive. Despite significant genome-sequencing efforts, the PAR of highly...
The molecular characteristics of the pseudoautosomal region (PAR) of sex chromosomes remain elusive. Despite significant genome-sequencing efforts, the PAR of highly differentiated avian sex chromosomes remains to be identified. Here we use linkage analysis together with whole-genome re-sequencing to uncover the 630-kb PAR of an ecological model species, the collared flycatcher. The PAR contains 22 protein-coding genes and is GC rich. The genetic length is 64 cM in female meiosis, consistent with an obligate crossing-over event. Recombination is concentrated to a hotspot region, with an extreme rate of >700 cM/Mb in a 67-kb segment. We find no signatures of sexual antagonism and propose that sexual antagonism may have limited influence on PAR sequences when sex chromosomes are nearly fully differentiated and when a recombination hotspot region is located close to the PAR boundary. Our results demonstrate that a very small PAR suffices to ensure homologous recombination and proper segregation of sex chromosomes during meiosis.
Topics: Animals; Female; Genetic Linkage; Genome; Male; Models, Animal; Passeriformes; Recombination, Genetic; Sex Chromosomes
PubMed: 25378102
DOI: 10.1038/ncomms6448 -
Nature Jun 2020Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand...
Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation. How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.
Topics: Animals; Cell Cycle Proteins; Chromatin Assembly and Disassembly; Chromosome Pairing; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Female; Heterochromatin; Kinetics; Male; Meiosis; Mice; Minisatellite Repeats; Oocytes; Pseudoautosomal Regions; Recombination, Genetic; Sex Characteristics; Sister Chromatid Exchange; Spermatocytes; Ubiquitin-Protein Ligases
PubMed: 32461690
DOI: 10.1038/s41586-020-2327-4 -
Molecular Ecology Jul 2022Recombination strongly impacts sequence evolution by affecting the extent of linkage and the efficiency of selection. Here, we study recombination over the Z chromosome...
Recombination strongly impacts sequence evolution by affecting the extent of linkage and the efficiency of selection. Here, we study recombination over the Z chromosome in great reed warblers (Acrocephalus arundinaceus) using pedigree-based linkage mapping. This species has extended Z and W chromosomes ("neo-sex chromosomes") formed by a fusion between a part of chromosome 4A and the ancestral sex chromosomes, which provides a unique opportunity to assess recombination and sequence evolution in sex-linked regions of different ages. We assembled an 87.54 Mbp and 90.19 cM large Z with a small pseudoautosomal region (0.89 Mbp) at one end and the fused Chr4A-part at the other end of the chromosome. A prominent feature in our data was an extreme variation in male recombination rate along Z with high values at both chromosome ends, but an apparent lack of recombination over a substantial central section, covering 78% of the chromosome. The nonrecombining region showed a drastic loss of genetic diversity and accumulation of repeats compared to the recombining parts. Thus, our data emphasize a key role of recombination in affecting local levels of polymorphism. Nonetheless, the evolutionary rate of genes (dN/dS) did not differ between high and low recombining regions, suggesting that the efficiency of selection on protein-coding sequences can be maintained also at very low levels of recombination. Finally, the Chr4A-derived part showed a similar recombination rate as the part of the ancestral Z that did recombine, but its sequence characteristics reflected both its previous autosomal, and current Z-linked, recombination patterns.
Topics: Animals; Evolution, Molecular; Genetic Linkage; Male; Passeriformes; Polymorphism, Genetic; Recombination, Genetic; Sex Chromosomes
PubMed: 35578784
DOI: 10.1111/mec.16532 -
Blood Advances Aug 2018The Xg and CD99 antigens of the human Xg blood group system show a unique and sex-specific phenotypic relationship. The phenotypic relationship is believed to result...
The Xg and CD99 antigens of the human Xg blood group system show a unique and sex-specific phenotypic relationship. The phenotypic relationship is believed to result from transcriptional coregulation of the and genes, which span the pseudoautosomal boundary of the X and Y chromosomes. However, the molecular genetic background responsible for these blood groups has remained undetermined. During the present investigation, we initially conducted a pilot study aimed at individuals with different Xg/CD99 phenotypes; this used targeted next-generation sequencing of the genomic areas relevant to and This was followed by a large-scale association study that demonstrated a definite association between a single nucleotide polymorphism (SNP) rs311103 and the Xg/CD99 blood groups. The G and C genotypes of SNP rs311103 were associated with the Xg(a+)/CD99H and Xg(a-)/CD99L phenotypes, respectively. The rs311103 genomic region with the G genotype was found to have stronger transcription-enhancing activity by reporter assay, and this occurred specifically with erythroid-lineage cells. Such activity was absent when the same region with the C genotype was investigated. In silico analysis of the polymorphic rs311103 genomic regions revealed that a binding motif for members of the GATA transcription factor family was present in the rs311103[G] region. Follow-up investigations showed that the erythroid GATA1 factor is able to bind specifically to the rs311103[G] region and markedly stimulates the transcriptional activity of the rs311103[G] segment. The present findings identify the genetic basis of the erythroid-specific Xg/CD99 blood group phenotypes and reveal the molecular background of their formation.
Topics: 12E7 Antigen; Blood Group Antigens; Cell Adhesion Molecules; Chromosomes, Human, X; Chromosomes, Human, Y; Female; GATA1 Transcription Factor; Genotype; Humans; Male; Polymorphism, Single Nucleotide
PubMed: 30061310
DOI: 10.1182/bloodadvances.2018018879