Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline

The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation, including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline. In the male germline of Drosophila melanogaster, a novel but poorly understood form of sex chromosome-specific transcriptional regulation occurs that is distinct from canonical sex chromosome dosage compensation or meiotic inactivation. Previous work shows that expression of reporter genes driven by testis-specific promoters is considerably lower—approximately 3-fold or more—for transgenes inserted into X chromosome versus autosome locations. Here we characterize this transcriptional suppression of X-linked genes in the male germline and its evolutionary consequences. Using transgenes and transpositions, we show that most endogenous X-linked genes, not just testis-specific ones, are transcriptionally suppressed several-fold specifically in the Drosophila male germline. In wild-type testes, this sex chromosome-wide transcriptional suppression is generally undetectable, being effectively compensated by the gene-by-gene evolutionary recruitment of strong promoters on the X chromosome. We identify and experimentally validate a promoter element sequence motif that is enriched upstream of the transcription start sites of hundreds of testis-expressed genes; evolutionarily conserved across species; associated with strong gene expression levels in testes; and overrepresented on the X chromosome. These findings show that the expression of X-linked genes in the Drosophila testes reflects a balance between chromosome-wide epigenetic transcriptional suppression and long-term compensatory adaptation by sex-linked genes. Our results have broad implications for the evolution of gene expression in the Drosophila male germline and for genome evolution

Sex Chromosome-Specific Regulation in the \u3ci\u3eDrosophila\u3c/i\u3e Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation—the equalization of X chromosome gene expression in males and females— and meiotic sex chromosome inactivation (MSCI)—the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila

Sex Chromosome-Specific Regulation in the Drosophila Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation

Suppression of X-linked transgene reporters versus normal expression of endogenous X-linked genes suggest a novel form of X chromosome-specific regulation in Drosophila testes, instead of sex chromosome dosage compensation or meiotic inactivation

Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build- up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey\u27s discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD \u3c 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD

Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication

Evolution: From Autosomes to Sex Chromosomes — and Back

SummaryHeteromorphic sex chromosomes are thought to represent a terminal evolutionary endpoint due to their specialized gene content and chromosome-specific regulation. New findings, however, show that an ancient X chromosome reverted to an autosome in the lineage leading to Drosophila

Seed Production Estimation for Mountain Big Sagebrush (Artemisia tridentata ssp. vaseyana)

Seed production is an essential component of postdisturbance recovery for mountain big sagebrush (Artemisia tridentata Nutt, ssp vaseyana [Rydb] Beetle; MBS). We tested a method for rapid estimation of MBS seed production using measurements of inflorescence morphology. We measured total stem length, stem length from first branchlet to stem tip, stem diameter, fresh weight, and number of stem branchlets for 750 inflorescences collected from five central and southern Utah sites. Florets per inflorescence were counted to provide an estimate of seed production potential. We used regression analysis to assess associations between morphological traits and potential seed production and evaluated the efficiency and scalability of each measure for field application. Site means for morphological measures varied ∼2 to 11-fold while mean number of florets per inflorescence varied ∼ 8-fold. Inflorescence weight was the best predictor of seed production potential (P < 0.0001, r2 = 0.897), although correlations for all tested variables were highly significant. Among-site differences in regression equations for this relationship were not significant (P = 0.226), suggesting that a single conversion factor may have broad application. However, validation will require additional testing across a broader range of sites and field conditions. Scalable methods for efficient estimation of sagebrush seed production potential, such as those evaluated in this study, could be useful for managers charged with assessing variability in sagebrush community stability. © 2017 The Society for Range Management. Published by Elsevier Inc. All rights reserved.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information

Sex Chromosome-Specific Regulation in the \u3ci\u3eDrosophila\u3c/i\u3e Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation—the equalization of X chromosome gene expression in males and females— and meiotic sex chromosome inactivation (MSCI)—the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila

Nondestructive Age Estimation of Mountain Big Sagebrush (Artemisia tridentata ssp. vaseyana) Using Morphological Characteristics

Current methods for determining plant age of shrub species require destructive sampling and annual growth ring analysis on the primary stem. Although individual plant ages can frequently be determined in this manner, the method is time consuming and of limited value for plants that have lost stem wood from stem splitting and rot. Nondestructive methods for estimating big sagebrush (Artemisia tridentata Nutt.) plant age would be useful in assessing stand age structure and population dynamics at variable spatial scales. The purpose of this study was to test a suite of traits for potential use in estimating mountain big sagebrush (Artemisia tridentata ssp. vaseyana [Rydb.] Beetle) age. We evaluated traits including plant height, crown area, subcanopy litter depth, percent crown mortality, bark furrow depth, bark fiber length, circumference and diameter of plant basal stem, and circumference of secondary and tertiary branches. We measured and harvested basal cross-sections from 163 plants of varying sizes from five locations in central and south-central Utah. Plant age was determined from annual growth rings. Linear regression analyses revealed that stem diameter (r2 = 0.507 P < 0.0001) was the most highly correlated variable with plant age across all sites, followed by stem circumference (r2 = 0.474 P < 0.0001), secondary branch circumference (r2 = 0.360, P < 0.0001), tertiary branch circumference (r2 = 0.405, P < 0.0001), and bark fiber length (r2 = 0.373, P < 0.0001). Results support previous findings that stem girth has value for estimating mountain big sagebrush plant age and that this trait is a better indicator of age than any other tested traits. Although the relationship between stem diameter and plant age was significant, substantial stem size variability associated with plants of the same approximate age indicates that the method is most appropriate when precise age estimates are not required. This technique was developed specifically for mountain big sagebrush, but it is expected that it can be adapted for other sagebrush taxa. © 2019 The Society for Range ManagementThe Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information