Search tips
Search criteria

Results 1-4 (4)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
Econometric reviews  2013;33(1-4):10.1080/07474938.2013.807103.
This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low-dimensional vector of latent factors. The analyst is assumed to have access to a set of measurements generated by the latent factors. This approach has attractive features from both theoretical and practical points of view. Not only does it address the fundamental identification problem arising from the inability to observe the same person in both the treated and untreated states, but it also turns out to be straightforward to implement. Formulae are provided to compute mean treatment effects as well as their distributional versions. A Monte Carlo simulation study is carried out to illustrate how the methodology can easily be applied.
PMCID: PMC3811964  PMID: 24187431
Potential Outcomes; Treatment Effects; Bayesian; Counterfactual Distributions
2.  Segmental dataset and whole body expression data do not support the hypothesis that non-random movement is an intrinsic property of Drosophila retrogenes 
Several studies in Drosophila have shown excessive movement of retrogenes from the X chromosome to autosomes, and that these genes are frequently expressed in the testis. This phenomenon has led to several hypotheses invoking natural selection as the process driving male-biased genes to the autosomes. Metta and Schlötterer (BMC Evol Biol 2010, 10:114) analyzed a set of retrogenes where the parental gene has been subsequently lost. They assumed that this class of retrogenes replaced the ancestral functions of the parental gene, and reported that these retrogenes, although mostly originating from movement out of the X chromosome, showed female-biased or unbiased expression. These observations led the authors to suggest that selective forces (such as meiotic sex chromosome inactivation and sexual antagonism) were not responsible for the observed pattern of retrogene movement out of the X chromosome.
We reanalyzed the dataset published by Metta and Schlötterer and found several issues that led us to a different conclusion. In particular, Metta and Schlötterer used a dataset combined with expression data in which significant sex-biased expression is not detectable. First, the authors used a segmental dataset where the genes selected for analysis were less testis-biased in expression than those that were excluded from the study. Second, sex-biased expression was defined by comparing male and female whole-body data and not the expression of these genes in gonadal tissues. This approach significantly reduces the probability of detecting sex-biased expressed genes, which explains why the vast majority of the genes analyzed (parental and retrogenes) were equally expressed in both males and females. Third, the female-biased expression observed by Metta and Schlötterer is mostly found for parental genes located on the X chromosome, which is known to be enriched with genes with female-biased expression. Fourth, using additional gonad expression data, we found that autosomal genes analyzed by Metta and Schlötterer are less up regulated in ovaries and have higher chance to be expressed in meiotic cells of spermatogenesis when compared to X-linked genes.
The criteria used to select retrogenes and the sex-biased expression data based on whole adult flies generated a segmental dataset of female-biased and unbiased expressed genes that was unable to detect the higher propensity of autosomal retrogenes to be expressed in males. Thus, there is no support for the authors’ view that the movement of new retrogenes, which originated from X-linked parental genes, was not driven by selection. Therefore, selection-based genetic models remain the most parsimonious explanations for the observed chromosomal distribution of retrogenes.
PMCID: PMC3532075  PMID: 22950647
3.  Re-analysis of the larval testis data on meiotic sex chromosome inactivation revealed evidence for tissue-specific gene expression related to the drosophila X chromosome 
BMC Biology  2012;10:49.
Meiotic sex chromosome inactivation (MSCI) during spermatogenesis has been proposed as one of the evolutionary driving forces behind both the under-representation of male-biased genes on, and the gene movement out of, the X chromosome in Drosophila. However, the relevance of MSCI in shaping sex chromosome evolution is controversial. Here we examine two aspects of a recent study on testis gene expression (Mikhaylova and Nurminsky, BMC Biol 2011, 9:29) that failed to support the MSCI in Drosophila. First, Mikhaylova and Nurminsky found no differences between X-linked and autosomal genes based on the transcriptional profiling of the early testis development, and thus concluded that MSCI does not occur in D. melanogaster. Second, they also analyzed expression data from several D. melanogaster tissues and concluded that under-representation on the X chromosome is not an exclusive property of testis-biased genes, but instead, a general property of tissue-specific genes.
By re-analyzing the Mikhaylova and Nurminsky's testis data and the expression data on several D. melanogaster tissues, we made two major findings that refuted their original claims. First, the developmental testis data has generally greater experimental error than conventional analyses, which reduced significantly the power to detect chromosomal differences in expression. Nevertheless, our re-analysis observed significantly lower expression of the X chromosome in the genomic transcriptomes of later development stages of the testis, which is consistent with the MSCI hypothesis. Second, tissue-specific genes are also in general enriched with genes more expressed in testes than in ovaries, that is testis-biased genes. By completely excluding from the analyses the testis-biased genes, which are known to be under-represented in the X, we found that all the other tissue-specific genes are randomly distributed between the X chromosome and the autosomes.
Our findings negate the original study of Mikhaylova and Nurminsky, which concluded a lack of MSCI and generalized the pattern of paucity in the X chromosome for tissue-specific genes in Drosophila. Therefore, MSCI and other selection-based models such as sexual antagonism, dosage compensation, and meiotic-drive continue to be viable models as driving forces shaping the genomic distribution of male-related genes in Drosophila.
PMCID: PMC3391172  PMID: 22691264
4.  Stage-Specific Expression Profiling of Drosophila Spermatogenesis Suggests that Meiotic Sex Chromosome Inactivation Drives Genomic Relocation of Testis-Expressed Genes 
PLoS Genetics  2009;5(11):e1000731.
In Drosophila, genes expressed in males tend to accumulate on autosomes and are underrepresented on the X chromosome. In particular, genes expressed in testis have been observed to frequently relocate from the X chromosome to the autosomes. The inactivation of X-linked genes during male meiosis (i.e., meiotic sex chromosome inactivation—MSCI) was first proposed to explain male sterility caused by X-autosomal translocation in Drosophila, and more recently it was suggested that MSCI might provide the conditions under which selection would favor the accumulation of testis-expressed genes on autosomes. In order to investigate the impact of MSCI on Drosophila testis-expressed genes, we performed a global gene expression analysis of the three major phases of D. melanogaster spermatogenesis: mitosis, meiosis, and post-meiosis. First, we found evidence supporting the existence of MSCI by comparing the expression levels of X- and autosome-linked genes, finding the former to be significantly reduced in meiosis. Second, we observed that the paucity of X-linked testis-expressed genes was restricted to those genes highly expressed in meiosis. Third, we found that autosomal genes relocated through retroposition from the X chromosome were more often highly expressed in meiosis in contrast to their X-linked parents. These results suggest MSCI as a general mechanism affecting the evolution of some testis-expressed genes.
Author Summary
During the course of Drosophila evolution, genes expressed in males have accumulated on the autosomes. Meiotic sex chromosome X inactivation in males was proposed, among other hypotheses, as a selective force favoring the accumulation of testis-expressed genes on the autosomes. Under such a model, the inactivation of X-linked genes would favor the accumulation of testis-expressed genes in autosomes, wherein these genes would still be expressed. In this study, we observed meiotic expression reduction for X-linked genes in D. melanogaster through a global gene expression analysis in different phases of spermatogenesis, in agreement with MSCI. In order to test the effects of MSCI on the chromosomal distribution of testis-expressed genes, we analyzed their expression pattern throughout spermatogenesis. First, X chromosome underrepresentation was restricted to testis-biased genes over-expressed in meiosis. Second, we observed that the autosomal genes retroposed from the X chromosome more often showed complementary expression in meiosis to their X-linked parents. These results support MSCI in Drosophila, suggesting its mechanistic role in the evolution of testis-expressed genes.
PMCID: PMC2770318  PMID: 19936020

Results 1-4 (4)