The human Y chromosome is intriguing not only because it harbours the master-switch gene that determines gender but also because of its unusual evolutionary history. The Y chromosome evolved from an ...autosome, and its evolution has been characterized by massive gene decay. Recent whole-genome and transcriptome analyses of Y chromosomes in humans and other primates, in Drosophila species and in plants have shed light on the current gene content of the Y chromosome, its origins and its long-term fate. Furthermore, comparative analysis of young and old Y chromosomes has given further insights into the evolutionary and molecular forces triggering Y-chromosome degeneration and into the evolutionary destiny of the Y chromosome.
The mammalian Y chromosome is critical for male sex determination and spermatogenesis. However, linking each Y gene to specific aspects of male reproduction has been challenging. As the Y chromosome ...is notoriously hard to sequence and target, functional studies have mostly relied on transgene-rescue approaches using mouse models with large multi-gene deletions. These experimental limitations have oriented the field toward the search for a minimum set of Y genes necessary for male reproduction. Here, considering Y-chromosome evolutionary history and decades of discoveries, we review the current state of research on its function in spermatogenesis and reassess the view that many Y genes are disposable for male reproduction.
Heterochromatic regions of the genome are repeat-rich and poor in protein coding genes, and are therefore underrepresented in even the best genome assemblies. One of the most difficult regions of the ...genome to assemble are sex-limited chromosomes. The
Y chromosome is entirely heterochromatic, yet has wide-ranging effects on male fertility, fitness, and genome-wide gene expression. The genetic basis of this phenotypic variation is difficult to study, in part because we do not know the detailed organization of the Y chromosome. To study Y chromosome organization in
, we develop an assembly strategy involving the
enrichment of heterochromatic long single-molecule reads and use these reads to create targeted
assemblies of heterochromatic sequences. We assigned contigs to the Y chromosome using Illumina reads to identify male-specific sequences. Our pipeline extends the
reference genome by 11.9 Mb, closes 43.8% of the gaps, and improves overall contiguity. The addition of 10.6 MB of Y-linked sequence permitted us to study the organization of repeats and genes along the Y chromosome. We detected a high rate of duplication to the pericentric regions of the Y chromosome from other regions in the genome. Most of these duplicated genes exist in multiple copies. We detail the evolutionary history of one sex-linked gene family,
While the Y chromosome does not undergo crossing over, we observed high gene conversion rates within and between members of the
gene family,
, and
, compared to genome-wide estimates. Our results suggest that gene conversion and gene duplication play an important role in the evolution of Y-linked genes.
Mammalian sex chromosomes are highly conserved, and sex is determined by
on the Y chromosome. Two exceptional rodent groups in which some species lack a Y chromosome and
offer insights into how novel ...sex genes can arise and replace
, leading to sex chromosome turnover. However, intensive study over three decades has failed to reveal the identity of novel sex genes in either of these lineages. We here report our discovery of a male-specific duplication of an enhancer of
in the Amami spiny rat
, in which males and females have only a single X chromosome (XO/XO) and the Y chromosome and
are completely lost. We performed a comprehensive survey to detect sex-specific genomic regions in the spiny rat. Sex-related genomic differences were limited to a male-specific duplication of a 17-kb unit located 430 kb upstream of
on an autosome. Hi-C analysis using male spiny rat cells showed the duplicated region has potential chromatin interaction with
. The duplicated unit harbored a 1,262-bp element homologous to mouse enhancer 14 (Enh14), a candidate
enhancer that is functionally redundant in mice. Transgenic reporter mice showed that the spiny rat Enh14 can function as an embryonic testis enhancer in mice. Embryonic gonads of XX mice in which Enh14 was replaced by the duplicated spiny rat Enh14 showed increased
expression and decreased
expression. We propose that male-specific duplication of this
enhancer substituted for
function, defining a novel Y chromosome in the spiny rat.
The olive fruit fly, Bactrocera oleae, is the most important pest in the olive fruit agribusiness industry. This is because female flies lay their eggs in the unripe fruits and upon hatching the ...larvae feed on the fruits thus destroying them. The lack of a high-quality genome and other genomic and transcriptomic data has hindered progress in understanding the fly's biology and proposing alternative control methods to pesticide use.
Genomic DNA was sequenced from male and female Demokritos strain flies, maintained in the laboratory for over 45 years. We used short-, mate-pair-, and long-read sequencing technologies to generate a combined male-female genome assembly (GenBank accession GCA_001188975.2). Genomic DNA sequencing from male insects using 10x Genomics linked-reads technology followed by mate-pair and long-read scaffolding and gap-closing generated a highly contiguous 489 Mb genome with a scaffold N50 of 4.69 Mb and L50 of 30 scaffolds (GenBank accession GCA_001188975.4). RNA-seq data generated from 12 tissues and/or developmental stages allowed for genome annotation. Short reads from both males and females and the chromosome quotient method enabled identification of Y-chromosome scaffolds which were extensively validated by PCR.
The high-quality genome generated represents a critical tool in olive fruit fly research. We provide an extensive RNA-seq data set, and genome annotation, critical towards gaining an insight into the biology of the olive fruit fly. In addition, elucidation of Y-chromosome sequences will advance our understanding of the Y-chromosome's organization, function and evolution and is poised to provide avenues for sterile insect technique approaches.
Summary
With its vast territory and complex natural environment, China boasts rich cattle genetic resources. To gain the further insight into the genetic diversity and paternal origins of Chinese ...cattle, we analyzed the polymorphism of Y‐SNPs (UTY19 and ZFY10) and Y‐STRs (INRA189 and BM861) in 34 Chinese cattle breeds/populations, including 606 males representative of 24 cattle breeds/populations collected in this study as well as previously published data for 302 bulls. Combined genotypic data identified 14 Y‐chromosome haplotypes that represented three haplogroups. Y2‐104‐158 and Y2‐102‐158 were the most common taurine haplotypes detected mainly in northern and central China, whereas the indicine haplotype Y3‐88‐156 predominates in southern China. Haplotypes Y2‐108‐158, Y2‐110‐158, Y2‐112‐158 and Y3‐92‐156 were private to Chinese cattle. The population structure revealed by multidimensional scaling analysis differentiated Tibetan cattle from the other three groups of cattle. Analysis of molecular variance showed that the majority of the genetic variation was explained by the genetic differences among groups. Overall, our study indicates that Chinese cattle retain high paternal diversity (H = 0.607 ± 0.016) and probably much of the original lineages that derived from the domestication center in the Near East without strong admixture from commercial cattle carrying Y1 haplotypes.
Objective
To describe the prevalence of Y‐chromosome microdeletions in a multi‐ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing ...in men with Y chromosome microdeletions.
Patients and Methods
A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed.
Results
The prevalence of microdeletions was 4% (n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%), and partial AZFa (1.7%). A high follicle‐stimulating hormone level (P < 0.001) and a low sperm concentration (P < 0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of >0.5 million/mL. Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after microdissection testicular sperm extraction was 33.2% in men with AZFc microdeletion.
Conclusions
The prevalence of Y‐chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P < 0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.
Deciphering the functions of Y chromosome in mammals has been slow owing to the presence of repeats. Some of these repeats transcribe coding RNAs, the roles of which have been studied. Functions of ...the noncoding transcripts from Y chromosomal repeats however, remain unclear. While a majority of the genes expressed during spermatogenesis are autosomal, mice with different deletions of the long arm of the Y chromosome (Yq) were previously also shown to be characterized by subfertility, sterility and sperm abnormalities, suggesting the presence of effectors of spermatogenesis at this location. Here we report a set of novel noncoding RNAs from mouse Yq and explore their connection to some of the autosomal genes expressed in testis.
We describe a set of novel mouse male-specific Y long arm (MSYq)-derived long noncoding (lnc) transcripts, named Pirmy and Pirmy-like RNAs. Pirmy shows a large number of splice variants in testis. We also identified Pirmy-like RNAs present in multiple copies at different loci on mouse Y chromosome. Further, we identified eight differentially expressed autosome-encoded sperm proteins in a mutant mouse strain, XY
qdel (2/3 Yq-deleted). Pirmy and Pirmy-like RNAs have homology to 5'/3'UTRs of these deregulated autosomal genes. Several lines of experiments show that these short homologous stretches correspond to piRNAs. Thus, Pirmy and Pirmy-like RNAs act as templates for several piRNAs. In vitro functional assays reveal putative roles for these piRNAs in regulating autosomal genes.
Our study elucidates a set of autosomal genes that are potentially regulated by MSYq-derived piRNAs in mouse testis. Sperm phenotypes from the Yq-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of MSYq-derived ncRNAs in male sterility and speciation.
Despite the importance of Y‐chromosomes in evolution and sex determination, their heterochromatic, repeat‐rich nature makes them difficult to sequence (due, in part, to ambiguities in sequence ...alignment and assembly) and to genetically manipulate. Therefore, they generally remain poorly understood. For example, the Drosophila melanogaster Y‐chromosome, one of the most extensively studied Y‐chromosomes, is widely heterochromatic and composed mainly of highly repetitive sequences, with only a handful of expressed genes scattered throughout its length. Efforts to insert transgenes on this chromosome have thus far relied on either random insertion of transposons (sometimes harbouring ‘landing sites’ for subsequent integrations) with limited success or on chromosomal translocations, thereby limiting the types of Y‐chromosome‐related questions that could be explored. Here, we describe a versatile approach to site‐specifically insert transgenes on the Y‐chromosome in D. melanogaster via CRISPR/Cas9‐mediated homology‐directed repair. We demonstrate the ability to insert, and detect expression from, fluorescently marked transgenes at two specific locations on the Y‐chromosome, and we utilize these marked Y‐chromosomes to detect and quantify rare chromosomal nondisjunction effects. Finally, we discuss how this Y‐docking technique could be adapted to other insects to aid in the development of genetic control technologies for the management of insect disease vectors and pests.
Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be ...established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor β1-neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure-associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.
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