Sexually selected differences in warbler plumage are related to a putative inversion on the Z chromosome.

Large structural variants in the genome, such as inversions, may play an important role in producing population structure and local adaptation to the environment through suppression of recombination. However, relatively few studies have linked inversions to phenotypic traits that are sexually selected and may play a role in reproductive isolation. Here, we found that geographic differences in the sexually selected plumage of a warbler, the common yellowthroat (Geothlypis trichas), are largely due to differences in the Z (sex) chromosome (males are ZZ), which contains at least one putative inversion spanning 40% (31/77 Mb) of its length. The inversions on the Z chromosome vary dramatically east and west of the Appalachian Mountains, which provides evidence of cryptic population structure within the range of the most widespread eastern subspecies (G. t. trichas). In an eastern (New York) and western (Wisconsin) population of this subspecies, female prefer different male ornaments; larger black facial masks are preferred in Wisconsin and larger yellow breasts are preferred in New York. The putative inversion also contains genes related to vision, which could influence mating preferences. Thus, structural variants on the Z chromosome are associated with geographic differences in male ornaments and female choice, which may provide a mechanism for maintaining different patterns of sexual selection in spite of gene flow between populations of the same subspecies.

Two phases of gonadal sex differentiation in zebrafish with ZZ/ZW sex determination system.

Zebrafish sex chromosomes have been identified in the wild Nadia (NA) strain, and its sex determination belongs to the female-heterogametic ZZ/ZW system. Here, we investigate the correlation between ZZ/ZW sex chromosomes in the NA strain with sex-related factors, and sort out the complicated process of sex determination in zebrafish. Two phases exist during zebrafish sex differentiation. In the first phase, ZW gonads differentiate into juvenile ovary while ZZ gonads remain indifferent. In the second phase, ZW gonads either continue ovary development or undergo female-to-male transition, while ZZ gonads undergo direct male development. The W chromosome may contribute to the first phase while the abundance of germ cells and other factors may be involved in the second phase of sex differentiation in zebrafish.

Genome assemblies for Chromidotilapia guntheri (Teleostei: Cichlidae) identify a novel candidate gene for vertebrate sex determination, RIN3.

Advances in genome sequencing have greatly accelerated the identification of sex chromosomes in a variety of species. Many of these species have experienced structural rearrangements that reduce recombination between the sex chromosomes, allowing the accumulation of sequence differences over many megabases. Identification of the genes that are responsible for sex determination within these sometimes large regions has proved difficult. Here, we identify an XY sex chromosome system on LG19 in the West African cichlid fish Chromidotilapia guntheri in which the region of differentiation extends over less than 400 kb. We develop high-quality male and female genome assemblies for this species, which confirm the absence of structural variants, and which facilitate the annotation of genes in the region. The peak of differentiation lies within rin3, which has experienced several debilitating mutations on the Y chromosome. We suggest two hypotheses about how these mutations might disrupt endocytosis, leading to Mendelian effects on sexual development.

Sex chromosome turnover and biodiversity in fishes.

The impact of sex chromosomes and their turnover in speciation remains a subject of ongoing debate in the field of evolutionary biology. Fishes are the largest group of vertebrates, and they exhibit unparalleled sexual plasticity, as well as diverse sex-determining (SD) genes, sex chromosomes, and sex determination mechanisms. This diversity is hypothesized to be associated with the frequent turnover of sex chromosomes in fishes. Although it is evident that amh and amhr2 are repeatedly and independently recruited as SD genes, their relationship with the rapid turnover of sex chromosomes and the biodiversity of fishes remains unknown. We summarize the canonical models of sex chromosome turnover and highlight the vital roles of gene mutation and hybridization with empirical evidence. We revisit Haldane's rule and the large X-effect and propose the hypothesis that sex chromosomes accelerate speciation by multiplying genotypes via hybridization. By integrating recent findings on the turnover of SD genes, sex chromosomes, and sex determination systems in fish species, this review provides insights into the relationship between sex chromosome evolution and biodiversity in fishes.

[Live birth achieved by oocyte donation in a patient with 45,X/46,XY mixed gonadal dysgenesis: A case report and literature review].

OBJECTIVE: To investigate the etiology, diagnosis and treatment of 45,X/46,XY mixed gonadal dysgenesis and the patients' clinical characteristics of conception, pregnancy and delivery, with purpose of improving the treatment and pregnancy management of the patients. METHODS: We retrospectively analyzed the clinical data on a pregnant patient with 45,X/46,XY mixed gonadal dysgenesis. RESULTS: Based on the findings of hypoplasia of secondary sexual characteristics, streak gonads, chromosome karyotype incompatibility with social sex, and chromosome aberration in the gonadal tissue, the patient was diagnosed with 45,X/46,XY mixed gonadal dysgenesis, received oocyte donation and intracytoplasmic sperm injection-embryo transfer (ICSI-ET), and achieved a live birth. CONCLUSION: Female patients with 45,X/46,XY mixed gonadal dysgenesis are infertile, but can achieve pregnancy through oocyte donation. However, the incidence rates of pregnancy complications and abnormal delivery are higher in these patients than in normal females. The perinatal outcomes can be improved by efficient treatment and pregnancy management of the patients.

Refractory hypertension complicated with Turner syndrome: A case report.

Hypertension is commonly classified into essential hypertension and secondary hypertension, although definitive classification can be challenging in some cases. Here, we discussed a patient who admitted for refractory hypertension, exhibiting various clinical manifestations including inadequate estrogen secretion, underdeveloped secondary sexual characteristics, primary amenorrhea, short stature, multiple moles, and somatic abnormalities. The patient was finally diagnosed with Turner syndrome (TS) based on clinical findings and chromosomal analysis. The genetic karyotype identified was 46,X,i(X)(q10).

Discovery unbalanced DNA mixtures and evaluation mixing ratio via a droplet digital PCR method.

BACKGROUND: Small amounts of DNA from a perpetrator collected during crime-scene investigations can be masked by large amounts of DNA from the victim. These samples can provide important information for the perpetrator's conviction. Short tandem repeat (STR) detection system is not sensitive enough to detect trace amounts of minor components in unbalanced mixed DNA. We developed a system using droplet digital polymerase chain reaction (ddPCR) capable of discovering trace components and accurately determining the ratio of mixed DNA in extremely unbalanced mixtures. METHODS: The non-recombining regions of the X chromosome and Y chromosome were quantified in the DNA of male and female mixtures using duplex ddPCR. Absolute quantification of low-abundance portions of trace samples and unbalanced mixtures was done using different mixing ratios. RESULTS: The ddPCR system could be used to detect low-abundance samples with < 5 copies of DNA components in an extremely unbalanced mixture at a mixing ratio of 10000:1. The high sensitivity and specificity of the system could identify the mixing ratio of mixed DNA accurately. CONCLUSIONS: A ddPCR system was developed for evaluation of mixed samples of male DNA and female DNA. Our system could detect DNA quantities as low as 5 copies in extremely unbalanced mixed samples with good specificity and applicability. This method could assist forensic investigators in avoiding the omission of important physical evidence, and evaluating the ratio of mixed male/female trace samples.

Reaction to Diagnosis and Parental Concerns in Parents of Children and Young Adults With XYY Syndrome.

BACKGROUND: There is a growing interest in exploring parents' views on the benefits of early diagnosis and awareness of sex chromosome trisomies. However, only a few studies focus specifically on the experience of parents of children with XYY syndrome. The present study aimed to assess, in parents of individuals with XYY, the perceived severity of their children's condition, their level of satisfaction with the disclosure process and their concerns about their children's present and future condition. METHODS: A national online sample of 56 Italian parents of children and young adults diagnosed with XYY syndrome participated in the study. They filled out a specifically developed online survey that assessed their children's areas of concern, their experience with the disclosure process and their worries about their children's condition. RESULTS: Seventy per cent of the parents received a prenatal diagnosis, whereas 30% received a postnatal diagnosis. High individual variability was found in the parent report of their child's condition. The most frequent areas of concern were attention regulation, emotion control and behaviour control. Individuals with a postnatal diagnosis showed more severe profiles. Parents were generally dissatisfied with the disclosure process, with no differences between prenatal and postnatal disclosure. However, more than 50% of the parents who received a prenatal disclosure reported that their child's condition was less severe than they had expected. In contrast, only 11% of the parents with postnatal disclosure reported this situation. Parents' concerns were negatively related to global satisfaction with the disclosure process and the correspondence between current and expected conditions but positively associated with the child's severity level. CONCLUSIONS: The results suggest that clear and realistic information during the disclosure process to parents is needed in both prenatal and postnatal communication and may alleviate parents' concerns.

Beyond gene flow: (non)-parallelism of secondary contact in a pair of highly differentiated sibling species.

Replicated secondary contact zones can provide insights into the barriers to gene flow that are important during speciation and can reveal to which degree secondary contact may result in similar evolutionary outcomes. Here, we studied two secondary contact zones between highly differentiated Alpine butterflies of the genus Erebia using whole-genome resequencing data. We assessed the genomic relationships between populations and species and found hybridization to be rare, with no to little current or historical introgression in either contact zone. There are large similarities between contact zones, consistent with an allopatric origin of interspecific differentiation, with no indications for ongoing reinforcing selection. Consistent with expected reduced effective population size, we further find that scaffolds related to the Z-chromosome show increased differentiation compared to the already high levels across the entire genome, which could also hint towards a contribution of the Z chromosome to species divergence in this system. Finally, we detected the presence of the endosymbiont Wolbachia, which can cause reproductive isolation between its hosts, in all E. cassioides, while it appears to be fully or largely absent in contact zone populations of E. tyndarus. We discuss how this rare pattern may have arisen and how it may have affected the dynamics of speciation upon secondary contact.

Genomic Anatomy of Homozygous XX Females and YY Males Reveals Early Evolutionary Trajectory of Sex-determining Gene and Sex Chromosomes in Silurus Fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type II receptor (amhr2y), which is consistent with findings in 2 other Silurus species but on different chromosomes (Chr24 of Silurus meridionalis and Chr5 of Silurus asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Autosomal suppression of sex-ratio meiotic drive influences the dynamics of X and Y chromosome coevolution.

Sex-ratio meiotic drivers are selfish genes or gene complexes that bias the transmission of sex chromosomes resulting in skewed sex ratios. Existing theoretical models have suggested the maintenance of a four-chromosome equilibrium (with driving and standard X and suppressing and susceptible Y) in a cyclic dynamic, studies of natural populations have failed to capture this pattern. Although there are several plausible explanations for this lack of cycling, interference from autosomal suppressors has not been studied using a theoretical population genetic framework even though autosomal suppressors and Y-linked suppressors coexist in natural populations of some species. In this study, we use a simulation-based approach to investigate the influence of autosomal suppressors on the cycling of sex chromosomes. Our findings demonstrate that the presence of an autosomal suppressor can hinder the invasion of a Y-linked suppressor under some parameter space, thereby impeding the cyclic dynamics, or even the invasion of Y-linked suppression. Even when a Y-linked suppressor invades, the presence of an autosomal suppressor can prevent cycling. Our study demonstrates the potential role of autosomal suppressors in preventing sex chromosome cycling and provides insights into the conditions and consequences of maintaining both Y-linked and autosomal suppressors.

Sex chromosome turnover plays an important role in the maintenance of barriers to post-speciation introgression in willows.

Almost all species in the genus Salix (willow) are dioecious and willows have variable sex-determining systems, the role of this variation in maintaining species barriers is relatively untested. We first analyzed the sex determination systems (SDS) of two species, Salix cardiophylla and Salix interior, whose positions in the Salix phylogeny make them important for understanding a sex chromosome turnover that has been detected in their relatives, and that changed the system from male (XX/XY) to female (ZW/ZZ) heterogamety. We show that both species have male heterogamety, with sex-linked regions (SLRs) on chromosome 15 (termed a 15XY system). The SLRs occupy 21.3% and 22.8% of the entire reference chromosome, respectively. By constructing phylogenetic trees, we determined the phylogenetic positions of all the species with known SDSs. Reconstruction of ancestral SDS character states revealed that the 15XY system is likely the ancestral state in willows. Turnovers of 15XY to 15ZW and 15XY to 7XY likely contributed to early speciation in Salix and gave rise to major groups of the Vetrix and Salix clades. Finally, we tested introgression among species in the phylogenetic trees based on both autosomes and SLRs separately. Frequent introgression was observed among species with 15XY, 15ZW, and 7XY on autosomes, in contrast to the SLR datasets, which showed less introgression, and in particular no gene flow between 15ZW and 7XY species. We argue that, although SDS turnovers in willow speciation may not create complete reproductive barriers, the evolution of SLRs plays important roles in preventing introgression and maintaining species boundaries.

Research Priorities of Individuals and Families with Sex Chromosome Aneuploidies.

Sex chromosome aneuploidies (SCAs) are chromosomal variations that result from an atypical number of X and/or Y chromosomes. Combined, SCAs affect ~1/400 live births, including individuals with Klinefelter syndrome (47,XXY), Turner syndrome (45,X and variants), Double Y syndrome (47,XYY), Trisomy X (47,XXX), and rarer tetrasomies and pentasomies. Individuals with SCAs experience a wide variety of physical health, mental health, and healthcare experiences that differ from the standard population. To understand the priorities of the SCA community we surveyed participants in two large SCA registries, the Inspiring New Science in Guiding Healthcare in Turner Syndrome (INSIGHTS) Registry and the Generating Advancements in Longitudinal Analysis in X and Y Variations (GALAXY) Registry. 303/629 (48.1% response rate) individuals from 13 sites across the United States responded to the survey, including 251 caregivers and 52 self-advocates, with a range of ages from 3 weeks to 73 years old and represented SCAs including Turner syndrome, XXX, XXY, XYY, XXYY, and combined rare tetrasomies and pentasomies. Results demonstrate the priorities for physical health and emotional/behavioral health identified by the SCA community, as well as preferred types of research. All SCA subtypes indicated intervention studies as the top priority, emphasizing the need for researchers to focus on clinical treatments in response to priorities of the SCA community.

Comparative genomics illuminates karyotype and sex chromosome evolution of sharks.

Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.

Temporal sex specific brain gene expression pattern during early rat embryonic development.

Background: The classical concept of brain sex differentiation suggests that steroid hormones released from the gonads program male and female brains differently. However, several studies indicate that steroid hormones are not the only determinant of brain sex differentiation and that genetic differences could also be involved. Methods: In this study, we have performed RNA sequencing of rat brains at embryonic days 12 (E12), E13, and E14. The aim was to identify differentially expressed genes between male and female rat brains during early development. Results: Analysis of genes expressed with the highest sex differences showed that Xist was highly expressed in females having XX genotype with an increasing expression over time. Analysis of genes expressed with the highest male expression identified three early genes, Sry2, Eif2s3y, and Ddx3y. Discussion: The observed sex-specific expression of genes at early development confirms that the rat brain is sexually dimorphic prior to gonadal action on the brain and identifies Sry2 and Eif2s3y as early genes contributing to male brain development.

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

Evolution of sex-biased genes in Drosophila species with neo-sex chromosomes: Potential contribution to reducing the sexual conflict.

An advantage of sex chromosomes may be the potential to reduce sexual conflict because they provide a basis for selection to operate separately on females and males. However, evaluating the relationship between sex chromosomes and sexual conflict is challenging owing to the difficulty in measuring sexual conflict and substantial divergence between species with and without sex chromosomes. We therefore examined sex-biased gene expression as a proxy for sexual conflict in three sets of Drosophila species with and without young sex chromosomes, the so-called neo-sex chromosomes. In all sets, we detected more sex-biased genes in the species with neo-sex chromosomes than in the species without neo-sex chromosomes in larvae, pupae, and adult somatic tissues but not in gonads. In particular, many unbiased genes became either female- or male-biased after linkage to the neo-sex chromosomes in larvae, despite the low sexual dimorphism. For example, genes involved in metabolism, a key determinant for the rate of development in many animals, were enriched in the genes that acquired sex-biased expression on the neo-sex chromosomes at the larval stage. These genes may be targets of sexually antagonistic selection (i.e., large size and rapid development are selected for in females but selected against in males). These results indicate that acquiring neo-sex chromosomes may have contributed to a reduction in sexual conflict, particularly at the larval stage, in Drosophila..

Discordant Prenatal Cell-Free DNA Screening vs. Diagnostic Results of Sex Chromosome Aneuploidies: Implications for Newborn Screening and Genetic Counseling.

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling.

Transcriptomic and proteomic elucidation of Z chromosome dosage compensation in Helicoverpa armigera.

Transcriptomic data have been used to study sex chromosome dosage compensation (SCDC) in approximately 10 Lepidoptera ZW species, yielding a consensus compensation pattern of Z ≈ ZZ < AA . $$ \approx \mathrm{ZZ}<\mathrm{AA}. $$ It remains unclear whether this compensation pattern holds when examining more Lepidoptera ZW species and/or using proteomic data to analyse SCDC. Here we combined transcriptomic and proteomic data as well as transcriptional level of six individual Z genes to reveal the SCDC pattern in Helicoverpa armigera, a polyphagous lepidopteran pest of economic importance. Transcriptomic analysis showed that the Z chromosome expression of H. armigera was balanced between male and female but substantially reduced relative to autosome expression, exhibiting an SCDC pattern of Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ . When using H. amigera midgut proteomic data, the SCDC pattern of this species changed from Z ≈ ZZ < AA $$ \approx \mathrm{ZZ}<\mathrm{AA} $$ at transcriptomic level to Z = ZZ = AA at the proteomic level. RT-qPCR analysis of transcript abundance of six Z genes found that compensation for each Z gene could vary from no compensation to overcompensation, depending on the individual genes and tissues tested. These results demonstrate for the first time the existence of a translational compensation mechanism, which is operating in addition to a translational mechanism, such as has been reported in other lepidopteran species. And the transcriptional compensation mechanism functions to accomplish Z chromosome dosage balance between the sexes (M = F on the Z chromosome), whereas the translation compensation mechanism operates to achieve dosage compensation between Z chromosome and autosome (Z = AA).

Homology in Sex Determination in Two Distant Spiny Frogs, Nanorana quadranus and Quasipaa yei.

Sex determination is remarkably diverse, with frequent transitions between sex chromosomes, in amphibians. Under these transitions, some chromosomes are more likely to be recurrently co-opted as sex chromosomes, as they are often observed across deeply divergent taxa. However, little is known about the pattern of sex chromosome evolution among closely related groups. Here, we examined sex chromosome and sex determination in two spiny frogs, Nanorana quadranus and Quasipaa yei. We conducted an analysis of genotyping-by-sequencing (GBS) data from a total of 34 individuals to identify sex-specific makers, with the results verified by PCR. The results suggest that chromosome 1 is a homologous sex chromosome with an XY pattern in both species. This chromosome has been evolutionarily conserved across these closely related groups within a period of time. The DMRT1 gene is proposed to be implicated in homology across two distantly related spiny frog species as a putative candidate sex-determining gene. Harboring the DMRT1 gene, chromosome 1 would have been independently co-opted for sex determination in deeply divergent groups of anurans.