scholarly journals Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes

2021 ◽  
Author(s):  
Juraj Bergman ◽  
Mikkel Heide Schierup
Keyword(s):  
Sex Chromosomes ◽  
Evolutionary Dynamics ◽  
Mutagenic Effect ◽  
Great Apes ◽  
Strand Break ◽  
Male Meiosis ◽  
Pseudoautosomal Region ◽  
Telomeric Region ◽  
Male Recombination ◽  
Telomeric Sequences

The pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. As the largest point of contact between the X and Y, PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and associated mutational processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes and two archaic human genome sequences. We find that the PAR1 sequence is closer to nucleotide equilibrium than autosomal telomeric sequences. We detect a difference between long-term substitution patterns and extant diversity in PAR1 that is mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. Additionally, we detect excess C→G mutations in PAR1 of all great ape species, specific to the mutagenic effect of male recombination. Analysis of differences between frequencies of alleles segregating in females and males provided no evidence for sexually antagonistic selection in this region. Furthermore, despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence, as is the case for the X chromosome and the autosomes. Lastly, we study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis. Our study provides an unprecedented quantification of population genetic forces and insight into evolutionary processes governing PAR1 biology.

scholarly journals Evolutionary dynamics of the human pseudoautosomal regions

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009532
Author(s):  
Bruno Monteiro ◽  
Miguel Arenas ◽  
Maria João Prata ◽  
António Amorim
Keyword(s):  
Genetic Diversity ◽  
Evolutionary Dynamics ◽  
Male Meiosis ◽  
Normal Male ◽  
Male Recombination ◽  
Evolutionary Forces ◽  
Evolutionary Origins ◽  
Y Chromosomes ◽  
Pseudoautosomal Regions ◽  
Transmission Studies

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2. Comparisons were performed through allele diversities, linkage disequilibrium status and recombination frequencies within and between X and Y chromosomes. In agreement with previous studies, we confirmed the role of PAR1 as a male-specific recombination hotspot, but also observed similar characteristic patterns of diversity in both regions although male recombination occurs at PAR2 to a much lower extent (at least one recombination event at PAR1 and in ≈1% in normal male meioses at PAR2). Furthermore, we demonstrate that both PARs harbor significantly different allele frequencies between X and Y chromosomes, which could support that recombination is not sufficient to homogenize the pseudoautosomal gene pool or is counterbalanced by other evolutionary forces. Nevertheless, the observed patterns of diversity are not entirely explainable by sexually antagonistic selection. A better understanding of such processes requires new data from intergenerational transmission studies of PARs, which would be decisive on the elucidation of PARs evolution and their role in male-driven heterosomal aneuploidies.

Sex Chromosomes and Psychosis

1988 ◽  
Vol 153 (5) ◽  
pp. 675-683 ◽  
Author(s):  
T. J. Crow
Keyword(s):  
Sex Chromosomes ◽  
Distal Segment ◽  
Depressive Illness ◽  
Male Meiosis ◽  
High Rate ◽  
Pseudoautosomal Region ◽  
Psychiatric Disease ◽  
Same Sex ◽  
Y Chromosomes ◽  
Gender Influences

Although the incidence of the recurrent psychoses (bipolar affective illness and schizophrenia) in the two sexes is approximately equal, gender influences a number of aspects of major psychiatric disease: unipolar depressive illness is twice as common in females, onset of schizophrenia is earlier and outcome is worse in males, and pairs of psychotic first-degree relatives are more often than expected of the same sex. In addition, sex chromosomal aneuploidies (e.g. XXY and XXX) are more frequent in patients with psychosis. Some of these findings can be explained if there is a major locus of predisposition to psychiatric disease in the ‘pseudoautosomal’ region of the sex chromosomes – that distal segment of the short arms in which there is genetic exchange between X and Y chromosomes at male meiosis. A gene located here would be transmitted in an autosomal manner, but would be passed above chance expectation to children of the same sex when inherited through a male. In that this segment of the sex chromosomes is subject to a high rate of recombination (which could generate new mutations), and may include determinants of brain lateralisation, it appears that the pseudoautosomal region could carry the genes which predispose to the major psychoses.

scholarly journals The Location of the Pseudoautosomal Boundary in Silene latifolia

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 610
Author(s):  
Marc Krasovec ◽  
Yu Zhang ◽  
Dmitry A. Filatov
Keyword(s):  
Genetic Map ◽  
Sex Chromosomes ◽  
Male Meiosis ◽  
Silene Latifolia ◽  
Pseudoautosomal Region ◽  
Wild Populations ◽  
Y Chromosomes ◽  
Polymorphism Data ◽  
Fuzzy Boundary ◽  
Over Time

Y-chromosomes contain a non-recombining region (NRY), and in many organisms it was shown that the NRY expanded over time. How and why the NRY expands remains unclear. Young sex chromosomes, where NRY expansion occurred recently or is on-going, offer an opportunity to study the causes of this process. Here, we used the plant Silene latifolia, where sex chromosomes evolved ~11 million years ago, to study the location of the boundary between the NRY and the recombining pseudoautosomal region (PAR). The previous work devoted to the NRY/PAR boundary in S. latifolia was based on a handful of genes with locations approximately known from the genetic map. Here, we report the analysis of 86 pseudoautosomal and sex-linked genes adjacent to the S. latifolia NRY/PAR boundary to establish the location of the boundary more precisely. We take advantage of the dense genetic map and polymorphism data from wild populations to identify 20 partially sex-linked genes located in the “fuzzy boundary”, that rarely recombines in male meiosis. Genes proximal to this fuzzy boundary show no evidence of recombination in males, while the genes distal to this partially-sex-linked region are actively recombining in males. Our results provide a more accurate location for the PAR boundary in S. latifolia, which will help to elucidate the causes of PAR boundary shifts leading to NRY expansion over time.

scholarly journals rahu is a mutant allele of Dnmt3c, encoding a DNA methyltransferase homolog required for meiosis and transposon repression in the mouse male germline

2017 ◽  
Author(s):  
Devanshi Jain ◽  
Cem Meydan ◽  
Julian Lange ◽  
Corentin Claeys Bouuaert ◽  
Christopher E. Mason ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Evolutionary Dynamics ◽  
Strand Break ◽  
Transcription Unit ◽  
Male Meiosis ◽  
Forward Genetics ◽  
Binding Interface ◽  
Male Germline ◽  
Cytosine Methyltransferase

AbstractTranscriptional silencing by heritable cytosine-5 methylation is an ancient strategy to repress transposable elements. It was previously thought that mammals possess four DNA methyltransferase paralogs—Dnmt1, Dnmt3a, Dnmt3b and Dnmt3l—that establish and maintain cytosine-5 methylation. Here we identify a fifth paralog, Dnmt3c, that is essential for retrotransposon methylation and repression in the mouse male germline. From a phenotype-based forward genetics screen, we isolated a mutant mouse called ‘rahu’, which displays severe defects in double-strand-break repair and homologous chromosome synapsis during male meiosis, resulting in sterility. rahu is an allele of a transcription unit (Gm14490, renamed Dnmt3c) that was previously mis-annotated as a Dnmt3-family pseudogene. Dnmt3c encodes a cytosine methyltransferase homolog, and Dnmt3crahu mutants harbor a non-synonymous mutation of a conserved residue within one of its cytosine methyltransferase motifs, similar to a mutation in human DNMT3B observed in patients with immunodeficiency, centromeric instability and facial anomalies syndrome. The rahu mutation lies at a potential dimerization interface and near the potential DNA binding interface, suggesting that it compromises protein-protein and/or protein-DNA interactions required for normal DNMT3C function in vivo. Dnmt3crahu mutant males fail to establish normal methylation within LINE and LTR retrotransposon sequences in the germline and accumulate higher levels of transposon-derived transcripts and proteins, particularly from distinct L1 and ERVK retrotransposon families. Phylogenetic analysis indicates that Dnmt3c arose during rodent evolution by tandem duplication of Dnmt3b, after the divergence of the Dipodoidea and Muroidea superfamilies. These findings provide insight into the evolutionary dynamics and functional specialization of the transposon suppression machinery critical for mammalian sexual reproduction and epigenetic regulation.

scholarly journals Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes

2001 ◽  
Vol 78 (1) ◽  
pp. 23-30 ◽  
Author(s):  
MARIKO KONDO ◽  
ERIKO NAGAO ◽  
HIROSHI MITANI ◽  
AKIHIRO SHIMA
Keyword(s):  
Genetic Map ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Oryzias Latipes ◽  
Male Recombination ◽  
Male And Female ◽  
Y Chromosomes ◽  
Genetic Length ◽  
Expressed Sequence ◽  
Group 1

In the medaka, Oryzias latipes, sex is determined chromosomally. The sex chromosomes differ from those of mammals in that the X and Y chromosomes are highly homologous. Using backcross panels for linkage analysis, we mapped 21 sequence tagged site (STS) markers on the sex chromosomes (linkage group 1). The genetic map of the sex chromosome was established using male and female meioses. The genetic length of the sex chromosome was shorter in male than in female meioses. The region where male recombination is suppressed is the region close to the sex-determining gene y, while female recombination was suppressed in both the telomeric regions. The restriction in recombination does not occur uniformly on the sex chromosome, as the genetic map distances of the markers are not proportional in male and female recombination. Thus, this observation seems to support the hypothesis that the heterogeneous sex chromosomes were derived from suppression of recombination between autosomal chromosomes. In two of the markers, Yc-2 and Casp6, which were expressed sequence-tagged (EST) sites, polymorphisms of both X and Y chromosomes were detected. The alleles of the X and Y chromosomes were also detected in O. curvinotus, a species related to the medaka. These markers could be used for genotyping the sex chromosomes in the medaka and other species, and could be used in other studies on sex chromosomes.

scholarly journals Subtelomeric Repeat Amplification Is Associated With Growth at Elevated Temperature in yku70 Mutants of Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1039-1051
Author(s):  
Barbara Fellerhoff ◽  
Friederike Eckardt-Schupp ◽  
Anna A Friedl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Elevated Temperature ◽  
Alternative Pathway ◽  
Dna Amplification ◽  
Strand Break ◽  
Significant Loss ◽  
Growth Defect ◽  
Slight Reduction ◽  
Telomeric Sequences ◽  
Repair Defect

Abstract Inactivation of the Saccharomyces cerevisiae gene YKU70 (HDF1), which encodes one subunit of the Ku heterodimer, confers a DNA double-strand break repair defect, shortening of and structural alterations in the telomeres, and a severe growth defect at 37°. To elucidate the basis of the temperature sensitivity, we analyzed subclones derived from rare yku70 mutant cells that formed a colony when plated at elevated temperature. In all these temperature-resistant subclones, but not in cell populations shifted to 37°, we observed substantial amplification and redistribution of subtelomeric Y′ element DNA. Amplification of Y′ elements and adjacent telomeric sequences has been described as an alternative pathway for chromosome end stabilization that is used by postsenescence survivors of mutants deficient for the telomerase pathway. Our data suggest that the combination of Ku deficiency and elevated temperature induces a potentially lethal alteration of telomere structure or function. Both in yku70 mutants and in wild type, incubation at 37° results in a slight reduction of the mean length of terminal restriction fragments, but not in a significant loss of telomeric (C1-3A/TG1-3)n sequences. We propose that the absence of Ku, which is known to bind to telomeres, affects the telomeric chromatin so that its chromosome end-defining function is lost at 37°.

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.

scholarly journals ZZ/ZW Sex Determination with Multiple Neo-Sex Chromosomes is Common in Madagascan Chameleons of the Genus Furcifer (Reptilia: Chamaeleonidae)

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1020 ◽  
Author(s):  
Rovatsos ◽  
Altmanová ◽  
Augstenová ◽  
Mazzoleni ◽  
Velenský ◽  
...  
Keyword(s):  
Sex Determination ◽  
Sex Chromosomes ◽  
Comparative Genomic ◽  
Telomeric Sequences ◽  
Female Heterogamety ◽  
Chromosomal Variability ◽  
Determination System ◽  
Hybridization In Situ ◽  
Sex Determination System

Chameleons are well-known, highly distinctive lizards characterized by unique morphological and physiological traits, but their karyotypes and sex determination system have remained poorly studied. We studied karyotypes in six species of Madagascan chameleons of the genus Furcifer by classical (conventional stain, C-banding) and molecular (comparative genomic hybridization, in situ hybridization with rDNA, microsatellite, and telomeric sequences) cytogenetic approaches. In contrast to most sauropsid lineages, the chameleons of the genus Furcifer show chromosomal variability even among closely related species, with diploid chromosome numbers varying from 2n = 22 to 2n = 28. We identified female heterogamety with cytogenetically distinct Z and W sex chromosomes in all studied species. Notably, multiple neo-sex chromosomes in the form Z1Z1Z2Z2/Z1Z2W were uncovered in four species of the genus (F. bifidus, F. verrucosus, F. willsii, and previously studied F. pardalis). Phylogenetic distribution and morphology of sex chromosomes suggest that multiple sex chromosomes, which are generally very rare among vertebrates with female heterogamety, possibly evolved several times within the genus Furcifer. Although acrodontan lizards (chameleons and dragon lizards) demonstrate otherwise notable variability in sex determination, it seems that female heterogamety with differentiated sex chromosomes remained stable in the chameleons of the genus Furcifer for about 30 million years.

scholarly journals Sex Chromosomes and Internal Telomeric Sequences in Dormitator latifrons (Richardson 1844) (Eleotridae: Eleotrinae): An Insight into Their Origin in the Genus

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 659
Author(s):  
Fabilene Gomes Paim ◽  
Mauro Nirchio ◽  
Claudio Oliveira ◽  
Anna Rita Rossi
Keyword(s):  
Sex Chromosomes ◽  
Food Resource ◽  
5S Rdna ◽  
Molecular Techniques ◽  
Chromosomal Mapping ◽  
Nucleolar Organizer Regions ◽  
Neotropical Fish ◽  
Telomeric Repeats ◽  
Western Atlantic ◽  
Telomeric Sequences

The freshwater fish species Dormitator latifrons, commonly named the Pacific fat sleeper, is an important food resource in CentralSouth America, yet almost no genetic information on it is available. A cytogenetic analysis of this species was undertaken by standard and molecular techniques (chromosomal mapping of 18S rDNA, 5S rDNA, and telomeric repeats), aiming to describe the karyotype features, verify the presence of sex chromosomes described in congeneric species, and make inferences on chromosome evolution in the genus. The karyotype (2n = 46) is mainly composed of metacentric and submetacentic chromosomes, with nucleolar organizer regions (NORs) localized on the short arms of submetacentric pair 10. The presence of XX/XY sex chromosomes was observed, with the X chromosome carrying the 5S rDNA sequences. These heterochromosomes likely appeared before 1 million years ago, since they are shared with another derived Dormitator species (Dormitator maculatus) distributed in the Western Atlantic. Telomeric repeats hybridize to the terminal portions of almost all chromosomes; additional interstitial sites are present in the centromeric region, suggesting pericentromeric inversions as the main rearrangement mechanisms that has driven karyotypic evolution in the genus. The data provided here contribute to improving the cytogenetics knowledge of D. latifrons, offering basic information that could be useful in aquaculture farming of this neotropical fish.

scholarly journals Human Spermatogenesis Tolerates Massive Size Reduction of the Pseudoautosomal Region

2020 ◽  
Vol 12 (11) ◽  
pp. 1961-1964
Author(s):  
Maki Fukami ◽  
Yasuko Fujisawa ◽  
Hiroyuki Ono ◽  
Tomoko Jinno ◽  
Tsutomu Ogata
Keyword(s):  
Animal Studies ◽  
Male Meiosis ◽  
Size Reduction ◽  
Pseudoautosomal Region ◽  
Minimal Size ◽  
Y Chromosomes ◽  
Cytogenetic Analyses ◽  
Human Spermatogenesis ◽  
Complete Deletion ◽  
Chromosomal Recombination

Abstract Mammalian male meiosis requires homologous recombination between the X and Y chromosomes. In humans, such recombination occurs exclusively in the short arm pseudoautosomal region (PAR1) of 2.699 Mb in size. Although it is known that complete deletion of PAR1 causes spermatogenic arrest, no studies have addressed to what extent male meiosis tolerates PAR1 size reduction. Here, we report two families in which PAR1 partial deletions were transmitted from fathers to their offspring. Cytogenetic analyses revealed that a ∼400-kb segment at the centromeric end of PAR1, which accounts for only 14.8% of normal PAR1 and 0.26% and 0.68% of the X and Y chromosomes, respectively, is sufficient to mediate sex chromosomal recombination during spermatogenesis. These results highlight the extreme recombinogenic activity of human PAR1. Our data, in conjunction with previous findings from animal studies, indicate that the minimal size requirement of mammalian PARs to maintain male fertility is fairly small.

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