@misc{vensko_stone_2015, title={Recent progress and open questions in Drosophila dosage compensation}, volume={9}, ISSN={["1933-6942"]}, DOI={10.1080/19336934.2015.1074786}, abstractNote={Sexual dimorphism is observed in many traits across diverse taxa, and often it is quite extreme. Within a species, individuals of opposing sex can appear strikingly different, reflecting differences at the molecular level that may be similarly striking. Among the most extreme cases of such molecular sexual dimorphism is the quantity of sex chromosomes that each sex possesses. Hemizygous sex chromosomes are common to many species, and various mechanisms have evolved to regulate transcriptional activity to ensure appropriate sex chromosome-to-autosome gene expression stoichiometry. Among the most thoroughly investigated of these mechanisms is Drosophila melanogaster's male-specific lethal (MSL) complex-mediated dosage compensation. In Drosophila, the male X chromosome transcription is upregulated approximately two-fold in somatic tissues to counterbalance the effects of sex chromosome hemizygosity on transcript abundance. Despite dramatic advances in our understanding of the Drosophila dosage compensation, many questions remain unanswered, and our understanding of its molecular underpinnings remains incomplete. In this review, we synthesize recent progress in the field as a means to highlight open questions, including how the MSL complex targets the X chromosome, how dosage compensation has shaped evolution of X-linked genes, and the degree to which MSL complex-mediated dosage compensation varies in activity across somatic tissues.}, number={1}, journal={FLY}, author={Vensko, Steven P., II and Stone, Eric A.}, year={2015}, month={Jan}, pages={29–35} } @article{vensko_stone_2015, title={X-to-autosome expression and msl-2 transcript abundance correlate among Drosophila melanogaster somatic tissues}, volume={3}, ISSN={["2167-8359"]}, DOI={10.7717/peerj.771}, abstractNote={In Drosophila melanogaster, the male-specific lethal (MSL) complex has been studied extensively for its role in upregulating male X-linked genes. Recent advances in high-throughput technologies have improved our understanding of how the MSL complex mediates dosage compensation through chromosome-wide chromatin modifications. Most studies, however, have focused on cell line models that cannot reflect any potential heterogeneity of in vivo dosage compensation. Comparisons between cell line and organismal gene-level dosage compensation upregulation suggest the possibility of variation in MSL complex activity among somatic tissues. We hypothesize the degree, up to but not exceeding 2-fold, to which the MSL complex upregulates male X-linked genes varies quantitatively by tissue type. In this model, MSL complex abundance acts as a rheostat to control the extent of upregulation. Using publicly available expression data, we provide evidence for our model in Drosophila somatic tissues. Specifically, we find X-to-autosome expression correlates with the tissue-specific expression of msl-2 which encodes an essential male-specific component of the MSL complex. This result suggests MSL complex mediated dosage compensation varies quantitatively by tissue type. Furthermore, this result has consequences for models explaining the organismal-scale molecular and evolutionary consequences of MSL-mediated dosage compensation.}, journal={PEERJ}, author={Vensko, Steven P., II and Stone, Eric A.}, year={2015}, month={Feb} } @article{vensko_stone_2014, title={No Evidence for a Global Male-Specific Lethal Complex-Mediated Dosage Compensation Contribution to the Demasculinization of the Drosophila melanogaster X Chromosome}, volume={9}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0103659}, abstractNote={In Drosophila melanogaster males, the expression of X-linked genes is regulated by mechanisms that operate on a chromosomal scale. One such mechanism, male-specific lethal complex-dependent X-linked dosage compensation, is thought to broadly enhance the expression of male X-linked genes through two-fold transcriptional upregulation. The evolutionary consequences of this form of dosage compensation are not well understood, particularly with regard to genes more highly expressed in males. It has been observed the X chromosome arrangement of these male-biased genes is non-random, consistent with what one might expect if there is a selective advantage for male-biased genes to avoid dosage compensation. Separately, it has been noted that the male-specific lethal complex and its dosage compensation mechanism appear absent in some male tissues, thus providing a control for the selection hypothesis. Here we utilized publicly available datasets to reassess the arrangement of X-linked male-biased expressed genes after accounting for expression in tissues not dosage compensated by the male-specific lethal complex. Our results do not corroborate previous observations supporting organismal-wide detrimental effects by dosage compensation on X-linked male-biased expressed genes. We instead find no evidence that dosage compensation has played a role in the arrangement of dosage compensated male-biased genes on the X chromosome.}, number={8}, journal={PLOS ONE}, author={Vensko, Steven P., II and Stone, Eric A.}, year={2014}, month={Aug} } @article{li_vensko_belikoff_scott_2013, title={Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0056303}, DOI={10.1371/journal.pone.0056303}, abstractNote={Transformer (TRA) promotes female development in several dipteran species including the Australian sheep blowfly Lucilia cuprina, the Mediterranean fruit fly, housefly and Drosophila melanogaster. tra transcripts are sex-specifically spliced such that only the female form encodes full length functional protein. The presence of six predicted TRA/TRA2 binding sites in the sex-specific female intron of the L. cuprina gene suggested that tra splicing is auto-regulated as in medfly and housefly. With the aim of identifying conserved motifs that may play a role in tra sex-specific splicing, here we have isolated and characterized the tra gene from three additional blowfly species, L. sericata, Cochliomyia hominivorax and C. macellaria. The blowfly adult male and female transcripts differ in the choice of splice donor site in the first intron, with males using a site downstream of the site used in females. The tra genes all contain a single TRA/TRA2 site in the male exon and a cluster of four to five sites in the male intron. However, overall the sex-specific intron sequences are poorly conserved in closely related blowflies. The most conserved regions are around the exon/intron junctions, the 3′ end of the intron and near the cluster of TRA/TRA2 sites. We propose a model for sex specific regulation of tra splicing that incorporates the conserved features identified in this study. In L. sericata embryos, the male tra transcript was first detected at around the time of cellular blastoderm formation. RNAi experiments showed that tra is required for female development in L. sericata and C. macellaria. The isolation of the tra gene from the New World screwworm fly C. hominivorax, a major livestock pest, will facilitate the development of a “male-only” strain for genetic control programs.}, number={2}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Li, Fang and Vensko, Steven P. and Belikoff, Esther J. and Scott, Maxwell J.}, editor={Tear, GuyEditor}, year={2013}, month={Feb}, pages={e56303} }