Mammals have the oldest sex chromosome system known: the mammalian X and Y chromosomes evolved from ordinary autosomes beginning at least 180 million years ago. Despite their shared ancestry, ...mammalian Y chromosomes display enormous variation among species in size, gene content, and structural complexity. Several unique features of the Y chromosome-its lack of a homologous partner for crossing over, its functional specialization for spermatogenesis, and its high degree of sequence amplification-contribute to this extreme variation. However, amid this evolutionary turmoil many commonalities have been revealed that have contributed to our understanding of the selective pressures driving the evolution and biology of the Y chromosome. Two biological themes have defined Y-chromosome research over the past six decades: testis determination and spermatogenesis. A third biological theme begins to emerge from recent insights into the Y chromosome's roles beyond the reproductive tract-a theme that promises to broaden the reach of Y-chromosome research by shedding light on fundamental sex differences in human health and disease.
The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We ...reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sex differences abound in human health and disease, as they do in other mammals used as models. The extent to which sex differences are conserved at the molecular level across species and tissues is ...unknown. We surveyed sex differences in gene expression in human, macaque, mouse, rat, and dog, across 12 tissues. In each tissue, we identified hundreds of genes with conserved sex-biased expression-findings that, combined with genomic analyses of human height, explain ~12% of the difference in height between females and males. We surmise that conserved sex biases in expression of genes otherwise operating equivalently in females and males contribute to sex differences in traits. However, most sex-biased expression arose during the mammalian radiation, which suggests that careful attention to interspecies divergence is needed when modeling human sex differences.
In mammals, the Y chromosome plays the pivotal role in male sex determination and is essential for normal sperm production. Yet only three Y chromosomes have been completely sequenced to date-those ...of human, chimpanzee, and rhesus macaque. While Y chromosomes are notoriously difficult to sequence owing to their highly repetitive genomic landscapes, these dedicated sequencing efforts have generated tremendous yields in medical, biological, and evolutionary insight. Knowledge of the complex structural organization of the human Y chromosome and a complete catalog of its gene content have provided a deeper understanding of the mechanisms that generate disease-causing mutations and large-scale rearrangements. Variation among human Y-chromosome sequences has been an invaluable tool for understanding relationships among human populations. Comprehensive comparisons of the human Y-chromosome sequence with those of other primates have illuminated aspects of Y-chromosome evolutionary dynamics over much longer timescales (>25 million years compared with 100,000 years). The future sequencing of additional Y chromosomes will provide a basis for a more comprehensive understanding of the evolution of Y chromosomes and their roles in reproductive biology.
The reference sequence of structurally complex regions can only be obtained through a highly accurate clone-based approach that we call Single-Haplotype Iterative Mapping and Sequencing (SHIMS). In ...recent years, improvements to SHIMS have reduced the cost and time required by two orders of magnitude, but internally repetitive clones still require extensive manual effort to transform draft assemblies into reference-quality finished sequences. Here we describe SHIMS 3.0, using ultra-long nanopore reads to augment the Illumina data from SHIMS 2.0 assemblies and resolve internally repetitive structures. This greatly minimizes the need for manual finishing of Illumina-based draft assemblies, allowing a small team with no prior finishing experience to sequence challenging targets with high accuracy. This protocol proceeds from clone-picking to finished assemblies in 2 weeks for about $80 (USD) per clone. We recently used this protocol to produce reference sequence of structurally complex palindromes on chimpanzee and rhesus macaque X chromosomes. Our protocol provides access to structurally complex regions that would otherwise be inaccessible from whole-genome shotgun data or require an impractical amount of manual effort to generate an accurate assembly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene ...poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of the MSY derives from the ancestral autosomes that gave rise to the mammalian sex chromosomes. Instead, all but 45 of the MSY's genes belong to three acquired, massively amplified gene families that have no homologs on primate MSYs but do have acquired, amplified homologs on the mouse X chromosome. The complete mouse MSY sequence brings to light dramatic forces in sex chromosome evolution: lineage-specific convergent acquisition and amplification of X-Y gene families, possibly fueled by antagonism between acquired X-Y homologs. The mouse MSY sequence presents opportunities for experimental studies of a sex-specific chromosome in its entirety, in a genetically tractable model organism.
Although the mammalian X and Y chromosomes evolved from a single pair of autosomes, they are highly differentiated: the Y chromosome is dramatically smaller than the X and has lost most of its genes. ...The surviving genes are a specialized set with extraordinary evolutionary longevity. Most mammalian lineages have experienced delayed, or relatively recent, loss of at least one conserved Y-linked gene. An extreme example of this phenomenon is in the Japanese spiny rat, where the Y chromosome has disappeared altogether. In this species, many Y-linked genes were rescued by transposition to new genomic locations, but until our work presented here, this has been considered an isolated case.
We describe eight cases of genes that have relocated to autosomes in mammalian lineages where the corresponding Y-linked gene has been lost. These gene transpositions originated from either the X or Y chromosomes, and are observed in diverse mammalian lineages: occurring at least once in marsupials, apes, and cattle, and at least twice in rodents and marmoset. For two genes--EIF1AX/Y and RPS4X/Y--transposition to autosomes occurred independently in three distinct lineages.
Rescue of Y-linked gene loss through transposition to autosomes has previously been reported for a single isolated rodent species. However, our findings indicate that this compensatory mechanism is widespread among mammalian species. Thus, Y-linked gene loss emerges as an additional driver of gene transposition from the sex chromosomes, a phenomenon thought to be driven primarily by meiotic sex chromosome inactivation.
This cohort study evaluates data from the Intern Health Study and uses the 9-item Patient Health Questionnaire to estimate the prevalence of depression among surgical interns.
Purpose
COVID-19 pandemic has had long-standing consequences for all aspects of life. Although young people appear less susceptible to severe forms of physical illness due to the coronavirus, they ...have not escaped unscathed from its’ psychological impacts. The present study measured the content of worries in young people residing in the UK during the pandemic and how it varied with sociodemographic factors.
Methods
Between May and December 2020, UK-residing participants aged 12–25 years completed an online survey that presented participants with free-text fields to describe their top three worries over the last two weeks, in addition to demographic and other information. Cross-sectional data from 2560 participants (Males = 767; Female = 1793) was analyzed.
Results
Irrespective of sociodemographic, a majority of the participants reported worries related to academics, followed by social relationships, own physical health, social and work routines, and physical health of others. Significantly more females reported concerns about academics, finances, physical health, social and work routines, social relationships, mental health and emotions, and physical health of others. Expectedly, more older (18–25 years) than younger (12–17 years) participants reported concerns about career-prospects and finances, while more younger than older ones were worried about academics (98.41% vs. 80.90%). With respect to financial worries, a higher percentage of BAME (Black, Asian and Minority Ethnic) communities in the UK reported such worries. Ethnicity significantly predicted more worries about social relationships among White than BAME participants. Significant differences also existed across different SES groups regarding endorsement of a particular category of worry.
Conclusion
These findings highlight the need for tailored interventions depending on the major concerns for young people of different ages, sexes, ethnicities, and SES.
The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ...ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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