scholarly journals X and Y Chromosome Complement Influence Adiposity and Metabolism in Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1092-1104 ◽  
Author(s):  
Xuqi Chen ◽  
Rebecca McClusky ◽  
Yuichiro Itoh ◽  
Karen Reue ◽  
Arthur P. Arnold
Keyword(s):  
Body Weight ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Gonadal Hormones ◽  
Xy Model ◽  
Second Sex ◽  
Metabolic Variables ◽  
Novel Model

Abstract Three different models of MF1 strain mice were studied to measure the effects of gonadal secretions and sex chromosome type and number on body weight and composition, and on related metabolic variables such as glucose homeostasis, feeding, and activity. The 3 genetic models varied sex chromosome complement in different ways, as follows: 1) “four core genotypes” mice, comprising XX and XY gonadal males, and XX and XY gonadal females; 2) the XY* model comprising groups similar to XO, XX, XY, and XXY; and 3) a novel model comprising 6 groups having XO, XX, and XY chromosomes with either testes or ovaries. In gonadally intact mice, gonadal males were heavier than gonadal females, but sex chromosome complement also influenced weight. The male/female difference was abolished by adult gonadectomy, after which mice with 2 sex chromosomes (XX or XY) had greater body weight and percentage of body fat than mice with 1 X chromosome. A second sex chromosome of either type, X or Y, had similar effects, indicating that the 2 sex chromosomes each possess factors that influence body weight and composition in the MF1 genetic background. Sex chromosome complement also influenced metabolic variables such as food intake and glucose tolerance. The results reveal a role for the Y chromosome in metabolism independent of testes and gonadal hormones and point to a small number of X–Y gene pairs with similar coding sequences as candidates for causing these effects.

scholarly journals Gonadal hormones and sex chromosome complement differentially contribute to ethanol intake, preference, and relapse-like behavior in Four Core Genotypes mice

2021 ◽  
Author(s):  
Elizabeth A. Sneddon ◽  
Lindsay N. Rasizer ◽  
Natalie G. Cavalco ◽  
Asa H. Jaymes ◽  
Noah J. Ostlie ◽  
...  
Keyword(s):  
High Risk ◽  
Mouse Model ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Drinking Behavior ◽  
Chromosome Complement ◽  
Gonadal Hormones ◽  
Rodent Models ◽  
Male And Female ◽  
Drinking Behaviors

AbstractAlcohol use and high-risk alcohol drinking behaviors among women are rapidly rising. In rodent models, females typically consume more ethanol (EtOH) than males. Here, we used the Four Core Genotypes (FCG) mouse model to investigate the influence of gonadal hormones and sex chromosome complement to EtOH drinking behaviors. FCG mice were given access to escalating concentrations of EtOH in a two-bottle, 24-h continuous access drinking paradigm to assess consumption and preference. Relapse-like behavior was measured by assessing escalated intake following repeated cycles of deprivation and re-exposure. Twenty-four hour EtOH consumption was greater in mice with ovaries (Sry−), relative to those with testes, and in mice with the XX chromosome complement, relative to those with XY sex chromosomes. EtOH preference was higher in XX vs. XY mice but not influenced by gonad type. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). These results demonstrate that aspects of EtOH drinking behavior may be independently regulated by sex hormones and chromosomes and inform our understanding of the neurobiological mechanisms which contribute to EtOH dependence in male and female mice. Future investigation of the contribution of sex chromosomes to EtOH drinking behaviors is warranted.

Abstract 209: An XX Sex Chromosome Complement Promotes the Development of Obesity, Hypercholesterolemia and Atherosclerosis in Male and Female Ldlr -/- Mice Fed a Western Diet

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Yasir Alsiraj ◽  
Sean Thatcher ◽  
Heba M. Ali ◽  
Ryan Temel ◽  
Alan Daugherty ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Cardiovascular Diseases ◽  
Surface Area ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Atherosclerotic Lesion ◽  
Western Diet ◽  
Male Mice

Background: Underlying mechanisms contributing to sexual dimorphism of cardiovascular diseases are not well understood. Sex hormones are primary contributors to sexual dimorphism of cardiovascular diseases. By comparison, little is known regarding the contribution of genes on sex chromosomes (XX and XY) to sexual dimorphism of cardiovascular diseases, even though the X chromosome contains around 5% of the human genome. In this study, we hypothesized that genes on sex chromosomes influence the development of obesity, hypercholesterolemia and atherosclerosis. Methods and Results: Transgenic male mice with deletion of Sry from the Y-chromosome expressing Sry on autosomes (8-12 weeks of age) were bred to female Ldlr -/- mice to generate female and male mice with an XX or an XY sex chromosome complement (FXX, FXY, MXX, MXY). Mice were fed a Western diet (Teklad TD88137) for 3 months. XX mice exhibited increased body weight compared to mice with an XY sex chromosome complement, regardless of gonadal sex (FXX, 41.2 ± 2.4; FXY, 31.7 ± 2.5 g; P<0.05; MXX, 51.5 ± 1.2; MXY, 41.7 ± 1.8 g; P<0.05). Moreover, XX mice had increased serum cholesterol concentrations, regardless of gonadal sex (FXX, 2501 ± 192; FXY, 890 ± 141 mg/dl; P<0.05; MXX, 3814 ± 344; MXY, 1297 ± 385 mg/dl; P<0.05). Elevations in serum lipids were manifest as increased VLDL and LDL-cholesterol. The extent of atherosclerosis in aortic arch was significantly increased in XX compared to XY mice (XXF, 37 ± 2.1; XYF, 20 ± 3.2; XXM, 38 ± 3.6; XYM, 24 ± 3.6 % lesion surface area; P<0.05). In the aortic sinus, atherosclerotic lesion surface area was significantly increased in XX mice, regardless of gonadal sex (FXX, 60.4 x 10 4 ± 3.6 x 10 4 ; FXY, 32.4 x 10 4 ± 3.8 x 10 4 μm 2 ; P<0.05; MXX, 67.1 x 10 4 ± 9.6 x 10 4 ; MXY, 36.2 x 10 4 ± 3.7 x 10 4 μm 2 ; P<0.05). Conclusion: Results demonstrate that an XX sex chromosome complement promotes diet-induced obesity, hypercholesterolemia and atherosclerosis regardless of gonadal sex. Future studies will identify the role of genes on the X or Y chromosome as mechanisms for these effects.

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

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.

scholarly journals Meiotic Behavior of Achiasmate Sex Chromosomes in the African Pygmy Mouse Mus mattheyi Offers New Insights into the Evolution of Sex Chromosome Pairing and Segregation in Mammals

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1434
Author(s):  
Ana Gil-Fernández ◽  
Marta Ribagorda ◽  
Marta Martín-Ruiz ◽  
Pablo López-Jiménez ◽  
Tamara Laguna ◽  
...  
Keyword(s):  
Dna Repair ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Mammalian Species ◽  
Evolutionary Process ◽  
Small Region ◽  
Pseudoautosomal Region ◽  
Evolution Of Sex ◽  
African Pygmy Mouse

X and Y chromosomes in mammals are different in size and gene content due to an evolutionary process of differentiation and degeneration of the Y chromosome. Nevertheless, these chromosomes usually share a small region of homology, the pseudoautosomal region (PAR), which allows them to perform a partial synapsis and undergo reciprocal recombination during meiosis, which ensures their segregation. However, in some mammalian species the PAR has been lost, which challenges the pairing and segregation of sex chromosomes in meiosis. The African pygmy mouse Mus mattheyi shows completely differentiated sex chromosomes, representing an uncommon evolutionary situation among mouse species. We have performed a detailed analysis of the location of proteins involved in synaptonemal complex assembly (SYCP3), recombination (RPA, RAD51 and MLH1) and sex chromosome inactivation (γH2AX) in this species. We found that neither synapsis nor chiasmata are found between sex chromosomes and their pairing is notably delayed compared to autosomes. Interestingly, the Y chromosome only incorporates RPA and RAD51 in a reduced fraction of spermatocytes, indicating a particular DNA repair dynamic on this chromosome. The analysis of segregation revealed that sex chromosomes are associated until metaphase-I just by a chromatin contact. Unexpectedly, both sex chromosomes remain labelled with γH2AX during first meiotic division. This chromatin contact is probably enough to maintain sex chromosome association up to anaphase-I and, therefore, could be relevant to ensure their reductional segregation. The results presented suggest that the regulation of both DNA repair and epigenetic modifications in the sex chromosomes can have a great impact on the divergence of sex chromosomes and their proper transmission, widening our understanding on the relationship between meiosis and the evolution of sex chromosomes in mammals.

Polymorphism and differentiation of rainbow trout Y chromosomes

Genome ◽  
2004 ◽  
Vol 47 (6) ◽  
pp. 1105-1113 ◽  
Author(s):  
Alicia Felip ◽  
Atushi Fujiwara ◽  
William P Young ◽  
Paul A Wheeler ◽  
Marc Noakes ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Morphological Differentiation ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Y Chromosomes ◽  
Cytogenetic Analyses ◽  
Clonal Lines ◽  
Sex Locus

Most fish species show little morphological differentiation in the sex chromosomes. We have coupled molecular and cytogenetic analyses to characterize the male-determining region of the rainbow trout (Oncorhynchus mykiss) Y chromosome. Four genetically diverse male clonal lines of this species were used for genetic and physical mapping of regions in the vicinity of the sex locus. Five markers were genetically mapped to the Y chromosome in these male lines, indicating that the sex locus was located on the same linkage group in each of the lines. We also confirmed the presence of a Y chromosome morphological polymorphism among these lines, with the Y chromosomes from two of the lines having the more common heteromorphic Y chromosome and two of the lines having Y chromosomes morphologically similar to the X chromosome. The fluorescence in situ hybridization (FISH) pattern of two probes linked to sex suggested that the sex locus is physically located on the long arm of the Y chromosome. Fishes appear to be an excellent group of organisms for studying sex chromosome evolution and differentiation in vertebrates because they show considerable variability in the mechanisms and (or) patterns involved in sex determination.Key words: sex chromosomes, sex markers, cytogenetics, rainbow trout, fish.

scholarly journals Sex Differences in Ischemic Stroke Sensitivity Are Influenced by Gonadal Hormones, Not by Sex Chromosome Complement

2014 ◽  
Vol 35 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Bharti Manwani ◽  
Kathryn Bentivegna ◽  
Sharon E Benashski ◽  
Venugopal Reddy Venna ◽  
Yan Xu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Sex Hormones ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Serum Testosterone ◽  
Gonadal Hormones ◽  
Epidemiologic Studies ◽  
Artery Occlusion ◽  
Male Mice

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

scholarly journals Extreme heterogeneity in sex chromosome differentiation and dosage compensation in livebearers

2019 ◽  
Vol 116 (38) ◽  
pp. 19031-19036 ◽  
Author(s):  
Iulia Darolti ◽  
Alison E. Wright ◽  
Benjamin A. Sandkam ◽  
Jake Morris ◽  
Natasha I. Bloch ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosomes ◽  
Poecilia Reticulata ◽  
Sex Chromosome ◽  
Sequencing Data ◽  
Chromosome Differentiation ◽  
Y Chromosomes ◽  
Shared Ancestry ◽  
Suppressed Recombination

Once recombination is halted between the X and Y chromosomes, sex chromosomes begin to differentiate and transition to heteromorphism. While there is a remarkable variation across clades in the degree of sex chromosome divergence, far less is known about the variation in sex chromosome differentiation within clades. Here, we combined whole-genome and transcriptome sequencing data to characterize the structure and conservation of sex chromosome systems across Poeciliidae, the livebearing clade that includes guppies. We found that the Poecilia reticulata XY system is much older than previously thought, being shared not only with its sister species, Poecilia wingei, but also with Poecilia picta, which diverged roughly 20 million years ago. Despite the shared ancestry, we uncovered an extreme heterogeneity across these species in the proportion of the sex chromosome with suppressed recombination, and the degree of Y chromosome decay. The sex chromosomes in P. reticulata and P. wingei are largely homomorphic, with recombination in the former persisting over a substantial fraction. However, the sex chromosomes in P. picta are completely nonrecombining and strikingly heteromorphic. Remarkably, the profound degradation of the ancestral Y chromosome in P. picta is counterbalanced by the evolution of functional chromosome-wide dosage compensation in this species, which has not been previously observed in teleost fish. Our results offer important insight into the initial stages of sex chromosome evolution and dosage compensation.

scholarly journals Differential regulation of mouse hippocampal gene expression sex differences by chromosomal content and gonadal sex

2021 ◽  
Author(s):  
Sarah R Ocanas ◽  
Victor A Ansere ◽  
Kyla B Tooley ◽  
Niran Hadad ◽  
Ana J Chucair-Elliott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sex Differences ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Experimental Models ◽  
Ctcf Binding ◽  
Autosomal Gene ◽  
Sex Effects

Sex differences in the brain as they relate to health and disease are often overlooked in experimental models. Many neurological disorders, like Alzheimer's disease (AD), multiple sclerosis (MS), and autism, differ in prevalence between males and females. Sex differences originate either from differential gene expression on sex chromosomes or from hormonal differences, either directly or indirectly. To disentangle the relative contributions of genetic sex (XX v. XY) and gonadal sex (ovaries v. testes) to the regulation of hippocampal sex effects, we use the "sex-reversal" Four Core Genotype (FCG) mouse model which uncouples sex chromosome complement from gonadal sex. Transcriptomic and epigenomic analyses of hippocampal RNA and DNA from ~12 month old FCG mice, reveals differential regulatory effects of sex chromosome content and gonadal sex on X- versus autosome-encoded gene expression and DNA modification patterns. Gene expression and DNA methylation patterns on the X chromosome were driven primarily by sex chromosome content, not gonadal sex. The majority of DNA methylation changes involved hypermethylation in the XX genotypes (as compared to XY) in the CpG context, with the largest differences in CpG islands, promoters, and CTCF binding sites. Autosomal gene expression and DNA modifications demonstrated regulation by sex chromosome complement and gonadal sex. These data demonstrate the importance of sex chromosomes themselves, independent of hormonal status, in regulating hippocampal sex effects. Future studies will need to further interrogate specific CNS cell types, identify the mechanisms by which sex chromosome regulate autosomes, and differentiate organizational from activational hormonal effects.

scholarly journals Identification of sex chromosomes using genomic and cytogenetic methods in a range-expanding spider, Argiope bruennichi (Araneae: Araneidae)

2021 ◽  
Author(s):  
Monica M Sheffer ◽  
Mathilde M Cordellier ◽  
Martin Forman ◽  
Malte Grewoldt ◽  
Katharina Hoffmann ◽  
...  
Keyword(s):  
X Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Chromosome Complement ◽  
Gc Content ◽  
Sexually Dimorphic ◽  
Behavioral Experiments ◽  
X Chromosomes ◽  
Male Karyotype ◽  
And Behavior

Differences between sexes in growth, ecology and behavior strongly shape species biology. In some animal groups, such as spiders, it is difficult or impossible to identify the sex of juveniles. This information would be useful for field surveys, behavioral experiments, and ecological studies on e.g. sex ratios and dispersal. In species with sex chromosomes, sex can be determined based on the specific sex chromosome complement. Additionally, information on the sequence of sex chromosomes provides the basis for studying sex chromosome evolution. We combined cytogenetic and genomic data to identify the sex chromosomes in the sexually dimorphic spider Argiope bruennichi, and designed RT-qPCR sex markers. We found that genome size and GC content of this spider falls into the range reported for the majority of araneids. The male karyotype is formed by 24 acrocentric chromosomes with an X1X20 sex chromosome system, with little similarity between X chromosomes, suggesting origin of these chromosomes by X chromosome fission or early duplication of an X chromosome and subsequent independent differentiation of the copies. Our data suggest similarly sized X chromosomes in A. bruennichi. They are smaller chromosomes of the complement. Our findings open the door to new directions in spider evolutionary and ecological research.

scholarly journals Reference genome and transcriptome informed by the sex chromosome complement of the sample increases ability to detect sex differences in gene expression from RNA-Seq data

2019 ◽  
Author(s):  
Kimberly C. Olney ◽  
Sarah M. Brotman ◽  
Jocelyn P. Andrews ◽  
Valeria A. Valverde-Vesling ◽  
Melissa A. Wilson
Keyword(s):  
Sex Differences ◽  
Y Chromosome ◽  
Sequence Homology ◽  
Reference Genome ◽  
Sex Chromosome ◽  
Sequence Similarity ◽  
Chromosome Complement ◽  
Transcript Abundance ◽  
Rna Seq ◽  
Y Chromosomes

AbstractBackgroundHuman X and Y chromosomes share an evolutionary origin and, as a consequence, sequence similarity. We investigated whether sequence homology between the X and Y chromosomes affects alignment of RNA-Seq reads and estimates of differential expression. We tested the effects of using reference genomes and reference transcriptomes informed by the sex chromosome complement of the sample’s genome on measurements of RNA-Seq abundance and sex differences in expression.ResultsThe default genome includes the entire human reference genome (GRCh38), including the entire sequence of the X and Y chromosomes. We created two sex chromosome complement informed reference genomes. One sex chromosome complement informed reference genome was used for samples that lacked a Y chromosome; for this reference genome version, we hard-masked the entire Y chromosome. For the other sex chromosome complement informed reference genome, to be used for samples with a Y chromosome, we hard-masked only the pseudoautosomal regions of the Y chromosome, because these regions are duplicated identically in the reference genome on the X chromosome. We analyzed transcript abundance in the whole blood, brain cortex, breast, liver, and thyroid tissues from 20 genetic female (46, XX) and 20 genetic male (46, XY) samples. Each sample was aligned twice; once to the default reference genome and then independently aligned to a reference genome informed by the sex chromosome complement of the sample, repeated using two different read aligners, HISAT and STAR. We then quantified sex differences in gene expression using featureCounts to get the raw count estimates followed by Limma/Voom for normalization and differential expression. We additionally created sex chromosome complement informed transcriptome references for use in pseudo-alignment using Salmon. Transcript abundance was quantified twice for each sample; once to the default target transcripts and then independently to target transcripts informed by the sex chromosome complement of the sample.ConclusionsWe show that regardless of the choice of read aligner, using an alignment protocol informed by the sex chromosome complement of the sample results in higher expression estimates on the pseudoautosomal regions of the X chromosome in both genetic male and genetic female samples, as well as an increased number of unique genes being called as differentially expressed between the sexes. We additionally show that using a pseudo-alignment approach informed on the sex chromosome complement of the sample eliminates Y-linked expression in female XX samples.Author summaryThe human X and Y chromosomes share an evolutionary origin and sequence homology, including regions of 100% identity; this sequence homology can result in reads misaligning between the sex chromosomes, X and Y. We hypothesized that misalignment of reads on the sex chromosomes would confound estimates of transcript abundance if the sex chromosome complement of the sample is not accounted for during the alignment step. For example, because of shared sequence similarity, X-linked reads could misalign to the Y chromosome. This is expected to result in reduced expression for regions between X and Y that share high levels of homology. For this reason, we tested the effect of using a default reference genome versus a reference genome informed by the sex chromosome complement of the sample on estimates of transcript abundance in human RNA-Seq samples from whole blood, brain cortex, breast, liver, and thyroid tissues of 20 genetic female (46, XX) and 20 genetic male (46, XY) samples. We found that using a reference genome with the sex chromosome complement of the sample resulted in higher measurements of X-linked gene transcription for both male and female samples and more differentially expressed genes on the X and Y chromosomes. We additionally investigated the use of a sex chromosome complement informed transcriptome reference index for alignment free quantification protocols. We observed no Y-linked expression in female XX samples only when the transcript quantification was performed using a transcriptome reference index informed on the sex chromosome complement of the sample. We recommend that future studies requiring aligning RNA-Seq reads to a reference genome or pseudo-alignment with a transcriptome reference should consider the sex chromosome complement of their samples prior to running default pipelines.

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