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Nature Reviews. Genetics Aug 2017The properties of the human Y chromosome - namely, male specificity, haploidy and escape from crossing over - make it an unusual component of the genome, and have led to... (Review)
Review
The properties of the human Y chromosome - namely, male specificity, haploidy and escape from crossing over - make it an unusual component of the genome, and have led to its genetic variation becoming a key part of studies of human evolution, population history, genealogy, forensics and male medical genetics. Next-generation sequencing (NGS) technologies have driven recent progress in these areas. In particular, NGS has yielded direct estimates of mutation rates, and an unbiased and calibrated molecular phylogeny that has unprecedented detail. Moreover, the availability of direct-to-consumer NGS services is fuelling a rise of 'citizen scientists', whose interest in resequencing their own Y chromosomes is generating a wealth of new data.
Topics: Chromosomes, Human, Y; Genetics, Population; Humans; Phylogeny; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 28555659
DOI: 10.1038/nrg.2017.36 -
Genes Dec 2022The present equine genetic variation mirrors the deep influence of intensive breeding programs during the last 200 years. Here, we provide a comprehensive current state... (Review)
Review
The present equine genetic variation mirrors the deep influence of intensive breeding programs during the last 200 years. Here, we provide a comprehensive current state of knowledge on the trends and prospects on the variation in the equine male-specific region of the Y chromosome (MSY), which was assembled for the first time in 2018. In comparison with the other 12 mammalian species, horses are now the most represented, with 56 documented MSY genes. However, in contrast to the high variability in mitochondrial DNA observed in many horse breeds from different geographic areas, modern horse populations demonstrate extremely low genetic Y-chromosome diversity. The selective pressures employed by breeders using pedigree data (which are not always error-free) as a predictive tool represent the main cause of this lack of variation in the Y-chromosome. Nevertheless, the detailed phylogenies obtained by recent fine-scaled Y-chromosomal genotyping in many horse breeds worldwide have contributed to addressing the genealogical, forensic, and population questions leading to the reappraisal of the Y-chromosome as a powerful genetic marker to avoid the loss of biodiversity as a result of selective breeding practices, and to better understand the historical development of horse breeds.
Topics: Horses; Animals; Male; Y Chromosome; Phylogeny; Pedigree; Selective Breeding; Polymorphism, Single Nucleotide; Mammals
PubMed: 36553539
DOI: 10.3390/genes13122272 -
Cytogenetic and Genome Research 2023The Y chromosome is a haploid genome unique to males with no genes essential for life. It is easily transmitted to the next generation without being repaired by... (Review)
Review
The Y chromosome is a haploid genome unique to males with no genes essential for life. It is easily transmitted to the next generation without being repaired by recombination, even if a major genomic structural alteration occurs. On the other hand, the Y chromosome genome is basically a region transmitted only from father to son, reflecting a male-specific inheritance between generations. The Y chromosome exhibits genomic structural differences among different ethnic groups and individuals. The Y chromosome was previously thought to affect only male-specific phenotypes, but recent studies have revealed associations between the Y chromosomes and phenotypes common to both males and females, such as certain types of cancer and neuropsychiatric disorders. This evidence was discovered with the finding of the mosaic loss of the Y chromosome in somatic cells. This phenomenon is also affected by environmental factors, such as smoking and aging. In the past, functional analysis of the Y chromosome has been elucidated by assessing the function of Y chromosome-specific genes and the association between Y chromosome haplogroups and human phenotypes. These studies are currently being conducted intensively. Additionally, the recent advance of large-scale genome cohort studies has increased the amount of Y chromosome genomic information available for analysis, making it possible to conduct more precise studies of the relationship between genome structures and phenotypes. In this review, we will introduce recent analyses using large-scale genome cohort data and previously reported association studies between Y chromosome haplogroups and human phenotypes, such as male infertility, cancer, cardiovascular system traits, and neuropsychiatric disorders. The function and biological role of the Y chromosome in human phenotypes will also be discussed.
Topics: Female; Humans; Male; Chromosomes, Human, Y; Mosaicism; Infertility, Male; Neoplasms; Genomics; Y Chromosome
PubMed: 37562362
DOI: 10.1159/000531933 -
ELife Oct 2021The mammalian Y chromosome is critical for male sex determination and spermatogenesis. However, linking each Y gene to specific aspects of male reproduction has been... (Review)
Review
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.
Topics: Animals; Biological Evolution; Humans; Male; Mammals; Mice; Spermatogenesis; Y Chromosome
PubMed: 34606444
DOI: 10.7554/eLife.67345 -
Molecular Biology and Evolution Jan 2021The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy...
The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared with their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female preference for rare Y-linked color variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence.
Topics: Animals; Biological Evolution; Female; Haplotypes; Male; Poecilia; Polymorphism, Genetic; Y Chromosome
PubMed: 33022040
DOI: 10.1093/molbev/msaa257 -
International Journal of Molecular... Jun 2019It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have... (Review)
Review
It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved.
Topics: Animals; Blood Pressure; Cardiovascular Diseases; Humans; Immunity, Innate; Y Chromosome
PubMed: 31200567
DOI: 10.3390/ijms20122892 -
Arteriosclerosis, Thrombosis, and... Nov 2019
Topics: Atherosclerosis; Chromosomes, Human, Y; Genetic Variation; Humans; Inflammation
PubMed: 31644351
DOI: 10.1161/ATVBAHA.119.313369 -
Trends in Genetics : TIG Jul 2020Y chromosomes are typically viewed as genetic wastelands with few intact genes. Recent genomic analyses in Drosophila, however, show that gene gain is prominent on young... (Review)
Review
Y chromosomes are typically viewed as genetic wastelands with few intact genes. Recent genomic analyses in Drosophila, however, show that gene gain is prominent on young Y chromosomes. Meiosis- and RNAi-related genes often coamplify on recently formed X and Y chromosomes, are testis-expressed, and produce antisense transcripts and short RNAs. RNAi pathways are also involved in suppressing sex ratio drive in Drosophila. These observations paint a dynamic picture of sex chromosome differentiation, suggesting that rapidly evolving genomic battles over segregation are rampant on young sex chromosomes and utilize RNAi to defend the genome against selfish elements that manipulate fair meiosis. Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.
Topics: Animals; Drosophila; Evolution, Molecular; Female; Genetic Fitness; Genome; Male; Meiosis; Selection, Genetic; Sex Ratio; Y Chromosome
PubMed: 32448494
DOI: 10.1016/j.tig.2020.04.008 -
Proceedings. Biological Sciences Oct 2020The coordination between mitochondrial and nuclear genes is crucial to eukaryotic organisms. Predicting the nature of these epistatic interactions can be difficult...
The coordination between mitochondrial and nuclear genes is crucial to eukaryotic organisms. Predicting the nature of these epistatic interactions can be difficult because of the transmission asymmetry of the genes involved. While autosomes and X-linked genes are transmitted through both sexes, genes on the Y chromosome and in the mitochondrial genome are uniparentally transmitted through males and females, respectively. Here, we generate 36 otherwise isogenic strains differing only in the geographical origin of their mitochondrial genome and Y chromosome, to experimentally examine the effects of the uniparentally inherited parts of the genome, as well as their interaction, in males. We assay longevity and gene expression through RNA-sequencing. We detect an important role for both mitochondrial and Y-linked genes, as well as extensive mitochondrial-Y chromosome epistasis. In particular, genes involved in male reproduction appear to be especially sensitive to such interactions, and variation on the Y chromosome is associated with differences in longevity. Despite these interactions, we find no evidence that the mitochondrial genome and Y chromosome are co-adapted within a geographical region. Overall, our study demonstrates a key role for the uniparentally inherited parts of the genome for male biology, but also that mito-nuclear interactions are complex and not easily predicted from simple transmission asymmetries.
Topics: Animals; Cell Nucleus; DNA, Mitochondrial; Drosophila melanogaster; Epistasis, Genetic; Female; Genes, Y-Linked; Genome, Mitochondrial; Longevity; Male; Mitochondria; Y Chromosome
PubMed: 33081607
DOI: 10.1098/rspb.2020.0469 -
Nature Ecology & Evolution Aug 2023While sex chromosomes carry sex-determining genes, they also often differ from autosomes in size and composition, consisting mainly of silenced heterochromatic...
While sex chromosomes carry sex-determining genes, they also often differ from autosomes in size and composition, consisting mainly of silenced heterochromatic repetitive DNA. Even though Y chromosomes show structural heteromorphism, the functional significance of such differences remains elusive. Correlative studies suggest that the amount of Y chromosome heterochromatin might be responsible for several male-specific traits, including sex-specific differences in longevity observed across a wide spectrum of species, including humans. However, experimental models to test this hypothesis have been lacking. Here we use the Drosophila melanogaster Y chromosome to investigate the relevance of sex chromosome heterochromatin in somatic organs in vivo. Using CRISPR-Cas9, we generated a library of Y chromosomes with variable levels of heterochromatin. We show that these different Y chromosomes can disrupt gene silencing in trans, on other chromosomes, by sequestering core components of the heterochromatin machinery. This effect is positively correlated to the level of Y heterochromatin. However, we also find that the ability of the Y chromosome to affect genome-wide heterochromatin does not generate physiological sex differences, including sexual dimorphism in longevity. Instead, we discovered that it is the phenotypic sex, female or male, that controls sex-specific differences in lifespan, rather than the presence of a Y chromosome. Altogether, our findings dismiss the 'toxic Y' hypothesis that postulates that the Y chromosome leads to reduced lifespan in XY individuals.
Topics: Humans; Animals; Female; Male; Drosophila melanogaster; Sex Characteristics; Heterochromatin; Longevity; Y Chromosome
PubMed: 37308701
DOI: 10.1038/s41559-023-02089-7