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PLoS Genetics Nov 2020Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are...
Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are thought to have evolved through an addition-attrition cycle involving the addition of autosomal segments to sex chromosomes and their subsequent differentiation. The events that drive this process are difficult to investigate because sex chromosomes in almost all mammals are at a very advanced stage of differentiation. Here, we have taken advantage of a recent translocation of an autosome to both sex chromosomes in the African pygmy mouse Mus minutoides, which has restored a large segment of homology (neo-PAR). By studying meiotic sex chromosome behavior and identifying fully sex-linked genetic markers in the neo-PAR, we demonstrate that this region shows unequivocal signs of early sex-differentiation. First, synapsis and resolution of DNA damage intermediates are delayed in the neo-PAR during meiosis. Second, recombination is suppressed or largely reduced in a large portion of the neo-PAR. However, the inactivation process that characterizes sex chromosomes during meiosis does not extend to this region. Finally, the sex chromosomes show a dual mechanism of association at metaphase-I that involves the formation of a chiasma in the neo-PAR and the preservation of an ancestral achiasmate mode of association in the non-homologous segments. We show that the study of meiosis is crucial to apprehend the onset of sex chromosome differentiation, as it introduces structural and functional constrains to sex chromosome evolution. Synapsis and DNA repair dynamics are the first processes affected in the incipient differentiation of X and Y chromosomes, and they may be involved in accelerating their evolution. This provides one of the very first reports of early steps in neo-sex chromosome differentiation in mammals, and for the first time a cellular framework for the addition-attrition model of sex chromosome evolution.
Topics: Animals; Eutheria; Female; Male; Mammals; Meiosis; Mice; Pseudoautosomal Regions; Sex Chromosomes; Sex Differentiation; Translocation, Genetic; X Chromosome; Y Chromosome
PubMed: 33180767
DOI: 10.1371/journal.pgen.1008959 -
Genome Research Apr 2019Here we use a chromosome-level genome assembly of a prairie rattlesnake (), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of...
Here we use a chromosome-level genome assembly of a prairie rattlesnake (), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and find evidence for partial dosage compensation driven by an evolutionary accumulation of a female-biased up-regulation mechanism. Comparative analyses with other amniotes provide new insight into the origins, structure, and function of reptile microchromosomes, which we demonstrate have markedly different structure and function compared to macrochromosomes. Snake microchromosomes are also enriched for venom genes, which we show have evolved through multiple tandem duplication events in multiple gene families. By overlaying chromatin structure information and gene expression data, we find evidence for venom gene-specific chromatin contact domains and identify how chromatin structure guides precise expression of multiple venom gene families. Further, we find evidence for venom gland-specific transcription factor activity and characterize a complement of mechanisms underlying venom production and regulation. Our findings reveal novel and fundamental features of reptile genome biology, provide insight into the regulation of snake venom, and broadly highlight the biological insight enabled by chromosome-level genome assemblies.
Topics: Animals; Chromatin; Chromosomes; Crotalid Venoms; Crotalus; Dosage Compensation, Genetic; Evolution, Molecular; Female; Male; Transcription Factors
PubMed: 30898880
DOI: 10.1101/gr.240952.118 -
Genetics Sep 2016Close relatives can share large segments of their genome identical by descent (IBD) that can be identified in genome-wide polymorphism data sets. There are a range of...
Close relatives can share large segments of their genome identical by descent (IBD) that can be identified in genome-wide polymorphism data sets. There are a range of methods to use these IBD segments to identify relatives and estimate their relationship. These methods have focused on sharing on the autosomes, as they provide a rich source of information about genealogical relationships. We hope to learn additional information about recent ancestry through shared IBD segments on the X chromosome, but currently lack the theoretical framework to use this information fully. Here, we fill this gap by developing probability distributions for the number and length of X chromosome segments shared IBD between an individual and an ancestor k generations back, as well as between half- and full-cousin relationships. Due to the inheritance pattern of the X and the fact that X homologous recombination occurs only in females (outside of the pseudoautosomal regions), the number of females along a genealogical lineage is a key quantity for understanding the number and length of the IBD segments shared among relatives. When inferring relationships among individuals, the number of female ancestors along a genealogical lineage will often be unknown. Therefore, our IBD segment length and number distributions marginalize over this unknown number of recombinational meioses through a distribution of recombinational meioses we derive. By using Bayes' theorem to invert these distributions, we can estimate the number of female ancestors between two relatives, giving us details about the genealogical relations between individuals not possible with autosomal data alone.
Topics: Bayes Theorem; Chromosomes, Human, X; Female; Genealogy and Heraldry; Genetic Variation; Genetics, Population; Genome-Wide Association Study; Humans; Inheritance Patterns; Male; Models, Genetic; Pedigree
PubMed: 27356612
DOI: 10.1534/genetics.116.190041 -
Journal of Medical Genetics Dec 2020Congenital clubfoot is a common birth defect that affects at least 0.1% of all births. Nearly 25% cases are familial and the remaining are sporadic in inheritance. Copy...
INTRODUCTION
Congenital clubfoot is a common birth defect that affects at least 0.1% of all births. Nearly 25% cases are familial and the remaining are sporadic in inheritance. Copy number variants (CNVs) involving transcriptional regulators of limb development, including and , have previously been shown to cause familial clubfoot, but much of the heritability remains unexplained.
METHODS
Exome sequence data from 816 unrelated clubfoot cases and 2645 in-house controls were analysed using coverage data to identify rare CNVs. The precise size and location of duplications were then determined using high-density Affymetrix Cytoscan chromosomal microarray (CMA). Segregation in families and status were determined using qantitative PCR.
RESULTS
Chromosome Xp22.33 duplications involving were identified in 1.1% of cases (9/816) compared with 0.07% of in-house controls (2/2645) (p=7.98×10, OR=14.57) and 0.27% (38/13592) of Atherosclerosis Risk in Communities/the Wellcome Trust Case Control Consortium 2 controls (p=0.001, OR=3.97). CMA validation confirmed an overlapping 180.28 kb duplicated region that included exons as well as downstream non-coding regions. In four of six sporadic cases where DNA was available for unaffected parents, the duplication was . The probability of four mutations in by chance in a cohort of 450 sporadic clubfoot cases is 5.4×10.
CONCLUSIONS
Microduplications of the pseudoautosomal chromosome Xp22.33 region (PAR1) containing and downstream enhancer elements occur in ~1% of patients with clubfoot. and regulatory regions have previously been implicated in skeletal dysplasia as well as idiopathic short stature, but have not yet been reported in clubfoot. duplications likely contribute to clubfoot pathogenesis by altering early limb development.
Topics: Adolescent; Child; Child, Preschool; Chromosome Duplication; Clubfoot; DNA Copy Number Variations; Gene Duplication; Genetic Predisposition to Disease; Humans; Infant; Microarray Analysis; Middle Aged; Paired Box Transcription Factors; Pedigree; Pseudoautosomal Regions; Short Stature Homeobox Protein; T-Box Domain Proteins; Exome Sequencing
PubMed: 32518174
DOI: 10.1136/jmedgenet-2020-106842 -
Science (New York, N.Y.) Dec 2014Sex-specific chromosomes, like the W of most female birds and the Y of male mammals, usually have lost most genes owing to a lack of recombination. We analyze newly...
Sex-specific chromosomes, like the W of most female birds and the Y of male mammals, usually have lost most genes owing to a lack of recombination. We analyze newly available genomes of 17 bird species representing the avian phylogenetic range, and find that more than half of them do not have as fully degenerated W chromosomes as that of chicken. We show that avian sex chromosomes harbor tremendous diversity among species in their composition of pseudoautosomal regions and degree of Z/W differentiation. Punctuated events of shared or lineage-specific recombination suppression have produced a gradient of "evolutionary strata" along the Z chromosome, which initiates from the putative avian sex-determining gene DMRT1 and ends at the pseudoautosomal region. W-linked genes are subject to ongoing functional decay after recombination was suppressed, and the tempo of degeneration slows down in older strata. Overall, we unveil a complex history of avian sex chromosome evolution.
Topics: Animals; Avian Proteins; Biological Evolution; Birds; Chickens; Chromosome Inversion; Chromosome Mapping; Evolution, Molecular; Female; Male; Phylogeny; Recombination, Genetic; Sex Chromosomes; Species Specificity; Struthioniformes; Synteny; Transcription Factors
PubMed: 25504727
DOI: 10.1126/science.1246338 -
BMC Genomics Mar 2021The larvacean Oikopleura dioica is an abundant tunicate plankton with the smallest (65-70 Mbp) non-parasitic, non-extremophile animal genome identified to date....
BACKGROUND
The larvacean Oikopleura dioica is an abundant tunicate plankton with the smallest (65-70 Mbp) non-parasitic, non-extremophile animal genome identified to date. Currently, there are two genomes available for the Bergen (OdB3) and Osaka (OSKA2016) O. dioica laboratory strains. Both assemblies have full genome coverage and high sequence accuracy. However, a chromosome-scale assembly has not yet been achieved.
RESULTS
Here, we present a chromosome-scale genome assembly (OKI2018_I69) of the Okinawan O. dioica produced using long-read Nanopore and short-read Illumina sequencing data from a single male, combined with Hi-C chromosomal conformation capture data for scaffolding. The OKI2018_I69 assembly has a total length of 64.3 Mbp distributed among 19 scaffolds. 99% of the assembly is contained within five megabase-scale scaffolds. We found telomeres on both ends of the two largest scaffolds, which represent assemblies of two fully contiguous autosomal chromosomes. Each of the other three large scaffolds have telomeres at one end only and we propose that they correspond to sex chromosomes split into a pseudo-autosomal region and X-specific or Y-specific regions. Indeed, these five scaffolds mostly correspond to equivalent linkage groups in OdB3, suggesting overall agreement in chromosomal organization between the two populations. At a more detailed level, the OKI2018_I69 assembly possesses similar genomic features in gene content and repetitive elements reported for OdB3. The Hi-C map suggests few reciprocal interactions between chromosome arms. At the sequence level, multiple genomic features such as GC content and repetitive elements are distributed differently along the short and long arms of the same chromosome.
CONCLUSIONS
We show that a hybrid approach of integrating multiple sequencing technologies with chromosome conformation information results in an accurate de novo chromosome-scale assembly of O. dioica's highly polymorphic genome. This genome assembly opens up the possibility of cross-genome comparison between O. dioica populations, as well as of studies of chromosomal evolution in this lineage.
Topics: Animals; Genome; Male; Nanopore Sequencing; Nanopores; Telomere; Urochordata
PubMed: 33781200
DOI: 10.1186/s12864-021-07512-6 -
Animal Bioscience Sep 2022The next generation sequencing has significantly contributed to clarify the genome structure of many species of zootechnical interest. However, to date, some portions of...
The next generation sequencing has significantly contributed to clarify the genome structure of many species of zootechnical interest. However, to date, some portions of the genome, especially those linked to a heterogametic nature such as the Y chromosome, are difficult to assemble and many gaps are still present. It is well known that the fluorescence in situ hybridization (FISH) is an excellent tool for identifying genes unequivocably mapped on chromosomes. Therefore, FISH can contribute to the localization of unplaced genome sequences, as well as to correct assembly errors generated by comparative bioinformatics. To this end, it is necessary to have starting points; therefore, in this study, we reviewed the physically mapped genes on the Y chromosome of cattle, buffalo, sheep, goats, pigs, horses and alpacas. A total of 208 loci were currently mapped by FISH. 89 were located in the malespecific region of the Y chromosome (MSY) and 119 were identified in the pseudoautosomal region (PAR). The loci reported in MSY and PAR were respectively: 18 and 25 in Bos taurus, 5 and 7 in Bubalus bubalis, 5 and 24 in Ovis aries, 5 and 19 in Capra hircus, 10 and 16 in Sus scrofa, 46 and 18 in Equus caballus. While in Vicugna pacos only 10 loci are reported in the PAR region. The correct knowledge and assembly of all genome sequences, including those of genes mapped on the Y chromosome, will help to elucidate their biological processes, as well as to discover and exploit potentially epistasis effects useful for selection breeding programs.
PubMed: 35240029
DOI: 10.5713/ab.21.0480 -
Molecules (Basel, Switzerland) Dec 2021In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of "reserve or maximum capacity of melatonin synthetic... (Review)
Review
In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of "reserve or maximum capacity of melatonin synthetic function" is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering / genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin's synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin's synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin's synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals.
Topics: Acetylserotonin O-Methyltransferase; Animals; Biosynthetic Pathways; Female; Humans; Male; Melatonin; Methyltransferases; Mitochondria; Sex Characteristics
PubMed: 34885890
DOI: 10.3390/molecules26237302 -
Scientific Reports Nov 2023We generated single haplotype assemblies from a hinny hybrid which significantly improved the gapless contiguity for horse and donkey autosomal genomes and the X...
We generated single haplotype assemblies from a hinny hybrid which significantly improved the gapless contiguity for horse and donkey autosomal genomes and the X chromosomes. We added over 15 Mb of missing sequence to both X chromosomes, 60 Mb to donkey autosomes and corrected numerous errors in donkey and some in horse reference genomes. We resolved functionally important X-linked repeats: the DXZ4 macrosatellite and ampliconic Equine Testis Specific Transcript Y7 (ETSTY7). We pinpointed the location of the pseudoautosomal boundaries (PAB) and determined the size of the horse (1.8 Mb) and donkey (1.88 Mb) pseudoautosomal regions (PARs). We discovered distinct differences in horse and donkey PABs: a testis-expressed gene, XKR3Y, spans horse PAB with exons1-2 located in Y and exon3 in the X-Y PAR, whereas the donkey XKR3Y is Y-specific. DXZ4 had a similar ~ 8 kb monomer in both species with 10 copies in horse and 20 in donkey. We assigned hundreds of copies of ETSTY7, a sequence horizontally transferred from Parascaris and massively amplified in equids, to horse and donkey X chromosomes and three autosomes. The findings and products contribute to molecular studies of equid biology and advance research on X-linked conditions, sex chromosome regulation and evolution in equids.
Topics: Male; Horses; Animals; Equidae; X Chromosome; Sex Chromosomes; Genome
PubMed: 37978222
DOI: 10.1038/s41598-023-47583-x -
Science Advances Jan 2022Faithful segregation of X and Y chromosomes requires meiotic recombination to form a crossover between them in the pseudoautosomal region (PAR). Unlike autosomes that...
Faithful segregation of X and Y chromosomes requires meiotic recombination to form a crossover between them in the pseudoautosomal region (PAR). Unlike autosomes that have approximately 10-fold more double-strand breaks (DSBs) than crossovers, one crossover must be formed from the one or two DSBs in PARs, implying the existence of a sex chromosome–specific recombination mechanism. Here, we found that RAD51AP2, a meiosis-specific partner of RAD51, is specifically required for the crossover formation on the XY chromosomes, but not autosomes. The decreased crossover formation between X and Y chromosomes in mutant mice results from compromised DSB repair in PARs due to destabilization of recombination intermediates rather than defects in DSB generation or synapsis. Our findings provide direct experimental evidence that XY recombination may use a PAR-specific DSB repair mechanism mediated by factors that are not essential for recombination on autosomes.
PubMed: 35020426
DOI: 10.1126/sciadv.abk1789