Has recombination changed during the recent evolution of the guppy Y chromosome?

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms. We used molecular markers to directly estimate genetic maps in sires from 4 guppy populations. The maps are very similar, suggesting that their crossover patterns have not recently changed. Our maps are consistent with population genomic results showing that variants within the terminal 5 Mb of the 26.5 Mb sex chromosome, chromosome 12, are most clearly associated with the maleness factor, albeit incompletely. We also confirmed occasional crossovers proximal to the male-determining region, defining a second, rarely recombining, pseudo-autosomal region, PAR2. This fish species may therefore have no completely male-specific region (MSY) more extensive than the male-determining factor. The positions of the few crossover events suggest a location for the male-determining factor within a physically small repetitive region. A sex-reversed XX male had few crossovers in PAR2, suggesting that this region's low crossover rate depends on the phenotypic, not the genetic, sex. Thus, rare individuals whose phenotypic and genetic sexes differ, and/or occasional PAR2 crossovers in males can explain the failure to detect fully Y-linked variants.

How did the guppy Y chromosome evolve?

The sex chromosome pairs of many species do not undergo genetic recombination, unlike the autosomes. It has been proposed that the suppressed recombination results from natural selection favouring close linkage between sex-determining genes and mutations on this chromosome with advantages in one sex, but disadvantages in the other (these are called sexually antagonistic mutations). No example of such selection leading to suppressed recombination has been described, but populations of the guppy display sexually antagonistic mutations (affecting male coloration), and would be expected to evolve suppressed recombination. In extant close relatives of the guppy, the Y chromosomes have suppressed recombination, and have lost all the genes present on the X (this is called genetic degeneration). However, the guppy Y occasionally recombines with its X, despite carrying sexually antagonistic mutations. We describe evidence that a new Y evolved recently in the guppy, from an X chromosome like that in these relatives, replacing the old, degenerated Y, and explaining why the guppy pair still recombine. The male coloration factors probably arose after the new Y evolved, and have already evolved expression that is confined to males, a different way to avoid the conflict between the sexes.

PromethION Sequencing and Assembly of the Genome of Micropoecilia picta, a Fish with a Highly Degenerated Y Chromosome.

We here describe sequencing and assembly of both the autosomes and the sex chromosome in Micropoecilia picta, the closest related species to the guppy, Poecilia reticulata. Poecilia (Micropoecilia) picta is a close outgroup for studying the guppy, an important organism for studies in evolutionary ecology and in sex chromosome evolution. The guppy XY pair (LG12) has long been studied as a test case for the importance of sexually antagonistic variants in selection for suppressed recombination between Y and X chromosomes. The guppy Y chromosome is not degenerated, but appears to carry functional copies of all genes that are present on its X counterpart. The X chromosomes of M. picta (and its relative Micropoecilia parae) are homologous to the guppy XY pair, but their Y chromosomes are highly degenerated, and no genes can be identified in the fully Y-linked region. A complete genome sequence of a M. picta male may therefore contribute to understanding how the guppy Y evolved. These fish species' genomes are estimated to be about 750 Mb, with high densities of repetitive sequences, suggesting that long-read sequencing is needed. We evaluated several assembly approaches, and used our results to investigate the extent of Y chromosome degeneration in this species.

Mental Health Outcomes Among British Healthcare Workers-Lessons From the First Wave of the Covid-19 Pandemic.

OBJECTIVE: To ascertain the level of psychological distress, using validated psychology tools, among British National healthcare workers (HCW) during the first wave of the Covid-19 crisis. METHODS: A multi-centre, anonymized, all-comer staff survey across 3 hospitals in Lancashire, England during the Covid-19 first wave (April to June 2020), consisting of Patient Health Questionnaire (PHQ-9), Perceived Stress Scale-10 (PSS-10), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Events Scale (IES-6). RESULTS: Among 1113 HCW, median (IQR) PHQ-9, GAD-7, PSS-10, and IES-6 score was 7 (3 to 11), 6 (3 to 11), 19 (13 to 24), and 9 (5 to 14), respectively. Potential predictors of higher levels of psychological distress included living alone, disabled dependents, history of depression/anxiety, and being female. CONCLUSIONS: The study indicates a high prevalence of psychological distress during the acute Covid-19 period among HCW, identifies groups at risk and areas of future research.

Locating the Sex Determining Region of Linkage Group 12 of Guppy (Poecilia reticulata).

Despite over 100 years of study, the location of the fully sex-linked region of the guppy (Poecilia reticulata) carrying the male-determining locus, and the regions where the XY pair recombine, remain unclear. Previous population genomics studies to determine these regions used small samples from recently bottlenecked captive populations, which increase the false positive rate of associations between individuals' sexes and SNPs. Using new data from multiple natural populations, we show that a recently proposed candidate for this species' male-determining gene is probably not completely sex-linked, leaving the maleness factor still unidentified. Variants in the chromosome 12 region carrying the candidate gene sometimes show linkage disequilibrium with the sex-determining factor, but no consistently male-specific variant has yet been found. Our genetic mapping with molecular markers spread across chromosome 12 confirms that this is the guppy XY pair. We describe two families with recombinants between the X and Y chromosomes, which confirm that the male-determining locus is in the region identified by all previous studies, near the terminal pseudo-autosomal region (PAR), which crosses over at a very high rate in males. We correct the PAR marker order, and assign two unplaced scaffolds to the PAR. We also detect a duplication, with one copy in the male-determining region, explaining signals of sex linkage in a more proximal region.

Using GC Content to Compare Recombination Patterns on the Sex Chromosomes and Autosomes of the Guppy, Poecilia reticulata, and Its Close Outgroup Species.

Genetic and physical mapping of the guppy (Poecilia reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, as in pseudoautosomal regions of mammalian sex chromosomes. We used GC content to indirectly infer recombination patterns on guppy chromosomes, based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. We used intron sequences and third positions of codons to make comparisons between sequences that are matched, as far as possible, and are all probably under weak selection. Almost all guppy chromosomes, including the sex chromosome (LG12), have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localization in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localization than the autosomes, or than the homologous chromosome in the close relative, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. We also identify the centromere ends of guppy chromosomes, which were not determined in the genome assembly.

Exaggerated heterochiasmy in a fish with sex-linked male coloration polymorphisms.

It is often stated that polymorphisms for mutations affecting fitness of males and females in opposite directions [sexually antagonistic (SA) polymorphisms] are the main selective force for the evolution of recombination suppression between sex chromosomes. However, empirical evidence to discriminate between different hypotheses is difficult to obtain. We report genetic mapping results in laboratory-raised families of the guppy (Poecilia reticulata), a sexually dimorphic fish with SA polymorphisms for male coloration genes, mostly on the sex chromosomes. Comparison of the genetic and physical maps shows that crossovers are distributed very differently in the two sexes (heterochiasmy); in male meiosis, they are restricted to the termini of all four chromosomes studied, including chromosome 12, which carries the sex-determining locus. Genome resequencing of male and female guppies from a population also indicates sex linkage of variants across almost the entire chromosome 12. More than 90% of the chromosome carrying the male-determining locus is therefore transmitted largely through the male lineage. A lack of heterochiasmy in a related fish species suggests that it originated recently in the lineage leading to the guppy. Our findings do not support the hypothesis that suppressed recombination evolved in response to the presence of SA polymorphisms. Instead, a low frequency of recombination on a chromosome that carries a male-determining locus and has not undergone genetic degeneration has probably facilitated the establishment of male-beneficial coloration polymorphisms.

Chemotherapy treatment and survival in older women with estrogen receptor-negative metastatic breast cancer: a population-based analysis.

UNLABELLED: To investigate the survival benefit associated with chemotherapy receipt in older women with estrogen receptor-negative (ER-) Stage IV breast cancer. DESIGN: Observational, retrospective cohort study using Cox proportional hazards regression to determine effect of chemotherapy on hazard of all-cause mortality. The two samples were an overall sample (n=1,519) and a propensity score-matched sample (n=580) to control for selection to treatment receipt. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained for regression models. SETTING: U.S. women within the National Cancer Institute Surveillance, Epidemiology and End Results cancer registries (SEER) linked to Medicare enrollment and claims database. PARTICIPANTS: Female Medicare beneficiaries aged 66 and older with Stage IV ER- breast cancer diagnosed between 1999 and 2005. MEASUREMENTS: Outcome measure was all-cause death during the follow-up period. Survival was measured as time from breast cancer diagnosis until death or last follow-up date. Information on receipt of chemotherapy, defined as chemotherapy received within 6 months after diagnosis, was obtained from linked Medicare claims. RESULTS: One thousand five hundred nineteen ER- women diagnosed with metastatic breast cancer were identified; 494 (33%) received chemotherapy. Chemotherapy was associated with a statistically significant survival benefit (HR=0.61, 95% CI=0.54-0.70). Age did not modify the survival benefit of chemotherapy. CONCLUSION: Chemotherapy received within 6 months after diagnosis was associated with a 39% lower hazard of death within the time period for the study. These findings reflect chemotherapy use outside of the clinical trial setting and have important clinical and policy implications for the study of treatments in older women with advanced ER- breast cancer.

Prehospital triage of acute myocardial infarction: wireless transmission of electrocardiograms to the on-call cardiologist via a handheld computer.

BACKGROUND: Use of intravenous fibrinolytic agents and percutaneous coronary interventions produce the greatest benefit when they are implemented in the first 2 hours after symptom onset. Further delays in the time to treatment typically lead to reduced benefits and poorer outcomes. METHODS: Cabarrus County Emergency Medical Service personnel complete an acute myocardial infarction case report form and assess a 12-lead electrocardiogram (ECG) to determine if ST elevation of at least 1 mV in at least 2 contiguous leads is present and then to transmit the ECG wirelessly to the emergency department (ED). The ECG is then forwarded wirelessly from the ED to the on-call cardiologist who is carrying the IPAQ handheld computer. RESULTS: Five representative patients managed using this system during the initial year of its implementation are presented. CONCLUSION: The examples included in this article illustrate that the system and technology can work if applied in a coordinated fashion using multiple disciplines including emergency medical service, cardiologists, ED personnel, and the hospital cardiac care team, which includes the catheterization laboratory call team, acute coronary care nurses, and clerical support staff.