The Masculinizer gene,Masc,encodes a lepidopteran-specific novel CCCHtype zinc finger protein,which controls sex determination and dosage compensation in Bombyx mori.Considering the potential application of it in pest...The Masculinizer gene,Masc,encodes a lepidopteran-specific novel CCCHtype zinc finger protein,which controls sex determination and dosage compensation in Bombyx mori.Considering the potential application of it in pest control,it is necessary to investigate the function of Masc gene in Hyphantria cunea,a globally invasive forest pest.In the present study,we identified and functionally characterized the Masc gene,HcMasc,in H.cunea.Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain,nuclear localization signal,and male determining domain,in which the last was confirmed to be required for its masculinization in BmN cell line.However,expression data showed that unlike male-biased expression in B.mori,Hc-Masc gene expresses in main all developmental stages or tissues in both sexes.Clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes.Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H.cunea and provide a foundation for developing better strategies to control this pest.展开更多
Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re rel...Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re relative global gene expression in diffe rent types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression.While previously available methods require a selective examination of specific genes,RNA sequencing provides a whole-genome view of gene expression in aneuploids.Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms.The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms.Thus,a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible,in both hypoploids and hyperploids,compared with euploid controls.Previous studies observed the inverse trans effect,in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region.This response was also the major type of changes found globally in this study.Many genes varied in dosage showed proportional expression changes,though some were seen to be partly or fully dosage compensated.It was also found that the effects of aneuploidy were progressive,with more severe aneuploids producing effects of greater magnitude.展开更多
A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of thi...A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of this chromosome -- the up-regulation of its expression to be equal to that of two X chromosomes in females. This hypothesis is evaluated in view of lesser known aspects of dosage compensation such as the fact that metafemales with three X chromosomes also have equal expression to normal females, which would require a down-regulation of each gene copy Moreover, when this complex is ectopically expressed in females or specifically targeted to a reporter in males, there is no increase in expression of the genes or targets with which it is associated. These observations are not consistent with the hypothesis that the MSL complex conditions dosage compensation. A synthesis is described that can account for these observations.展开更多
Sex determination system in birds is characterized by a homo-(Neognatae) and heteromorphic (Paleognatae) sex chromosomes. Heterogametic sex is female (ZZ/ZW system). DMRT1 gene is a gene regarded as a main male sex de...Sex determination system in birds is characterized by a homo-(Neognatae) and heteromorphic (Paleognatae) sex chromosomes. Heterogametic sex is female (ZZ/ZW system). DMRT1 gene is a gene regarded as a main male sex determining factor in this group of animals. The question remains about the participation of other factors (HEMOGEN, AMH etc.) in appearance of testis, and the role of steroid hormones in formation of ovaries. Complete sex inversion is not typical for species with genotypic sex determination (GSD), although the effect of estrogen metabolites is noted for birds. For birds epigenetic mechanisms of regulation (methylation of DNA and non-coding RNA) have been described for sex controlling genes such as CYP19A1 and DMRT1.展开更多
In the evolutionary model of dosage compensation,per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males(XY)compared to females(XX).How...In the evolutionary model of dosage compensation,per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males(XY)compared to females(XX).However,the expression regulation of X-linked genes is still controversial,and comprehensive evaluations are still lacking.By integrating multi-omics datasets in mammals,we investigated the expression ratios including X to autosomes(X:AA ratio)and X to orthologs(X:XX ratio)at the transcriptome,translatome,and proteome levels.We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice.Meanwhile,by tracing the evolution of orthologous gene expression in chickens,platypuses,and opossums,we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species(X:XX1)across tissues and developmental stages,demonstrating stable dosage compensation in mammals.We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression,thus affecting X:AA ratios.It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome,rather than the stable dosage compensation.展开更多
The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptio...The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex.However,owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes(S:A ratios)in different studies,we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species.We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes.We found that in mammals and birds,the S:A ratio is approximately 0.5,whereas in insects,fishes,and flatworms,the S:A ratio is approximately 1.0.Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the X/Z chromosome is significantly correlated with the S:A ratio.In addition,the degree of degeneration of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage compensation mechanism.Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that dosage sensitivity states of sex chromosomes are a major factor underlying different evolutionary strategies of dosage compensation.展开更多
基金funded by the Strategic Priority Research Program of Chinese Academy of Sciences(XDB11010600)National Natural Science Foundation of China(32101531 and 31420103918)National Key Research and Development Program of China,grant number 2018YFD0600203.
文摘The Masculinizer gene,Masc,encodes a lepidopteran-specific novel CCCHtype zinc finger protein,which controls sex determination and dosage compensation in Bombyx mori.Considering the potential application of it in pest control,it is necessary to investigate the function of Masc gene in Hyphantria cunea,a globally invasive forest pest.In the present study,we identified and functionally characterized the Masc gene,HcMasc,in H.cunea.Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain,nuclear localization signal,and male determining domain,in which the last was confirmed to be required for its masculinization in BmN cell line.However,expression data showed that unlike male-biased expression in B.mori,Hc-Masc gene expresses in main all developmental stages or tissues in both sexes.Clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes.Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H.cunea and provide a foundation for developing better strategies to control this pest.
基金This work was supported by the National Science Foundation grants IOS-1545780,NSF 1615789,and NSF 1853556。
文摘Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re relative global gene expression in diffe rent types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression.While previously available methods require a selective examination of specific genes,RNA sequencing provides a whole-genome view of gene expression in aneuploids.Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms.The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms.Thus,a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible,in both hypoploids and hyperploids,compared with euploid controls.Previous studies observed the inverse trans effect,in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region.This response was also the major type of changes found globally in this study.Many genes varied in dosage showed proportional expression changes,though some were seen to be partly or fully dosage compensated.It was also found that the effects of aneuploidy were progressive,with more severe aneuploids producing effects of greater magnitude.
基金supported by the National Institutes of Health grant of the United States(No.RO1GM068042)
文摘A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of this chromosome -- the up-regulation of its expression to be equal to that of two X chromosomes in females. This hypothesis is evaluated in view of lesser known aspects of dosage compensation such as the fact that metafemales with three X chromosomes also have equal expression to normal females, which would require a down-regulation of each gene copy Moreover, when this complex is ectopically expressed in females or specifically targeted to a reporter in males, there is no increase in expression of the genes or targets with which it is associated. These observations are not consistent with the hypothesis that the MSL complex conditions dosage compensation. A synthesis is described that can account for these observations.
文摘Sex determination system in birds is characterized by a homo-(Neognatae) and heteromorphic (Paleognatae) sex chromosomes. Heterogametic sex is female (ZZ/ZW system). DMRT1 gene is a gene regarded as a main male sex determining factor in this group of animals. The question remains about the participation of other factors (HEMOGEN, AMH etc.) in appearance of testis, and the role of steroid hormones in formation of ovaries. Complete sex inversion is not typical for species with genotypic sex determination (GSD), although the effect of estrogen metabolites is noted for birds. For birds epigenetic mechanisms of regulation (methylation of DNA and non-coding RNA) have been described for sex controlling genes such as CYP19A1 and DMRT1.
基金supported by the National Natural Science Foundation of China(Grant No.31871305)the Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology,China(Grant No.2020FB08)+1 种基金the Fundamental Research Funds for the Central Universities,China(Grant Nos.2662018PY021 and 2662019PY003)the Huazhong Agricultural University Scientific&Technological Self-innovation Foundation,China(Grant No.2016RC011).
文摘In the evolutionary model of dosage compensation,per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males(XY)compared to females(XX).However,the expression regulation of X-linked genes is still controversial,and comprehensive evaluations are still lacking.By integrating multi-omics datasets in mammals,we investigated the expression ratios including X to autosomes(X:AA ratio)and X to orthologs(X:XX ratio)at the transcriptome,translatome,and proteome levels.We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice.Meanwhile,by tracing the evolution of orthologous gene expression in chickens,platypuses,and opossums,we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species(X:XX1)across tissues and developmental stages,demonstrating stable dosage compensation in mammals.We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression,thus affecting X:AA ratios.It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome,rather than the stable dosage compensation.
基金supported by grants from the National Key R&D Program of China(2017YFA0103504 to X.C.and project number:2018ZX10301402 awarded to J.-R.Y.)the National Natural Science Foundation of China(project numbers:31771406 awarded to X.C.and 31671320,31871320,and 81830103 awarded to J.-R.Y.)
文摘The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems,as in at least one of the sexes,the sex-linked gene dose has been reduced by half.It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex.However,owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes(S:A ratios)in different studies,we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species.We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes.We found that in mammals and birds,the S:A ratio is approximately 0.5,whereas in insects,fishes,and flatworms,the S:A ratio is approximately 1.0.Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the X/Z chromosome is significantly correlated with the S:A ratio.In addition,the degree of degeneration of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage compensation mechanism.Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that dosage sensitivity states of sex chromosomes are a major factor underlying different evolutionary strategies of dosage compensation.
