Sex chromosome evolution results in the disparity in gene content between heterogametic sex chromosomes and creates the need for dosage compensation to counteract the effects of gene dose imbalance of sex chromosomes in males and females. It is not known at which stage of sex chromosome evolution dosage compensation would evolve. We used global gene expression profiling in male and female papayas to assess gene expression patterns of sex-linked genes on the papaya sex chromosomes. By analyzing expression ratios of sex-linked genes to autosomal genes and sex-linked genes in males relative to females, our results showed that dosage compensation was regulated on a gene-by-gene level rather than whole sex-linked region in papaya. Seven genes on the papaya X chromosome exhibited dosage compensation. We further compared gene expression ratios in the two evolutionary strata. Y alleles in the older evolutionary stratum showed reduced expression compared to X alleles, while Y alleles in the younger evolutionary stratum showed elevated expression compared to X alleles. Reduced expression of Y alleles in the older evolutionary stratum might be caused by accumulation of deleterious mutations in regulatory regions or transposable element-mediated methylation spreading. Most X-hemizygous genes exhibited either no or very low expression, suggesting that gene silencing might play a role in maintaining transcriptional balance between females and males.
Sex chromosomes frequently differ from the autosomes in the frequencies of genes with sexually dimorphic or tissue-specific expression. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments that have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (upregulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (downregulated) following treatment. We further show that whether a gene is bound by the dosage compensation complex in males can largely explain the paucity of both up- and downregulated genes on the X chromosome. Specifically, genes that are bound by the dosage compensation complex, or close to a dosage compensation complex high-affinity site, are unlikely to be up- or downregulated after treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that dosage compensation complex binding, or the associated chromatin modifications, inhibit both up- and downregulation of X chromosome gene expression within specific contexts, including tissue-specific expression. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first, a component of the dosage compensation complex, as a dampener of gene expression variance in both males and females. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific or induced expression, while the mammalian X has an excess of genes with tissue-specific expression.
more » « less- Award ID(s):
- 1845686
- PAR ID:
- 10370533
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- G3 Genes|Genomes|Genetics
- Volume:
- 12
- Issue:
- 9
- ISSN:
- 2160-1836
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Palli, Subba Reddy (Ed.)The transformer ( tra ) gene is essential for female development in many insect species, including the Australian sheep blow fly, Lucilia cuprina . Sex-specific tra RNA splicing is controlled by Sex lethal ( Sxl ) in Drosophila melanogaster but is auto-regulated in L . cuprina . Sxl also represses X chromosome dosage compensation in female D . melanogaster . We have developed conditional Lctra RNAi knockdown strains using the tet-off system. Four strains did not produce females on diet without tetracycline and could potentially be used for genetic control of L . cuprina . In one strain, which showed both maternal and zygotic tTA expression, most XX transformed males died at the pupal stage. RNAseq and qRT-PCR analyses of mid-stage pupae showed increased expression of X-linked genes in XX individuals. These results suggest that Lctra promotes somatic sexual differentiation and inhibits X chromosome dosage compensation in female L . cuprina . However, XX flies homozygous for a loss-of-function Lctra knockin mutation were fully transformed and showed high pupal eclosion. Two of five X-linked genes examined showed a significant increase in mRNA levels in XX males. The stronger phenotype in the RNAi knockdown strain could indicate that maternal Lctra expression may be essential for initiation of dosage compensation suppression in female embryos.more » « less
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Premise One evolutionary path from hermaphroditism to dioecy is via a gynodioecious intermediate. The evolution of dioecy may also coincide with the formation of sex chromosomes that possess sex‐determining loci that are physically linked in a region of suppressed recombination. Dioecious papaya (
Carica papaya ) has an XY chromosome system, where the presence of a Y chromosome determines maleness. However, in cultivation, papaya is gynodioecious, due to the conversion of the male Y chromosome to a hermaphroditic Yhchromosome during its domestication.Methods We investigated gene expression linked to the X, Y, and Yhchromosomes at different floral developmental stages to identify differentially expressed genes that may be involved in the sexual transition of males to hermaphrodites.
Results We identified 309 sex‐biased genes found on the sex chromosomes, most of which are found in the pseudoautosomal regions. Female (XX) expression in the sex‐determining region was almost double that of X‐linked expression in males (XY) and hermaphrodites (XYh), which rules out dosage compensation for most sex‐linked genes; although, an analysis of hemizygous X‐linked loci found evidence of partial dosage compensation. Furthermore, we identified a candidate gene associated with sex determination and the transition to hermaphroditism, a homolog of the MADS‐box protein
SHORT VEGETATIVE PHASE .Conclusions We identified a pattern of partial dosage compensation for hemizygous genes located in the papaya sex‐determining region. Furthermore, we propose that loss‐of‐expression of the Y‐linked
SHORT VEGETATIVE PHASE homolog facilitated the transition from males to hermaphrodites in papaya. -
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Abstract Dosage compensation in
Caenorhabditis elegans equalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin- containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression. Condensin IDCand an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC’s continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin IDCin X chromosome compaction, additional mechanisms contribute to X- linked gene repression. DPY-21, a non-condensin IDCDCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4 tethers H3K9me3-rich chromosomal regions to the nuclear lamina, which also contributes to X- linked gene repression. To investigate the necessity of condensin IDCduring the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin IDCsubunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin IDCwas no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression. These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin IDC. A loss-of-function mutation incec-4 , in addition to the depletion of DPY-27 or the genetic mutation ofdpy- 21 , led to even more significant increases in X-linked gene expression, suggesting that tethering heterochromatic regions to the nuclear lamina helps stabilize repression mediated by condensin IDCand H4K20me1.Author Summary In some organisms, whether an individual becomes male, female, or hermaphrodite is determined by the number of their sex chromosomes. In the nematode
Caenorhabditis elegans , males have one X chromosome, whereas hermaphrodites have two X chromosomes. This difference in the number of X chromosomes is crucial for deciding whether an individual becomes a hermaphrodite or a male. However, having two X chromosomes can lead to problems because it results in different gene expression levels, resulting in hermaphrodite lethality. To solve this issue, many organisms undergo a process called dosage compensation. Dosage compensation inC. elegans is achieved by a group of proteins known as the dosage compensation complex (DCC), which includes a protein called DPY-27. The function of DPY-27 is essential during early embryonic development. This study shows that in contrast to early embryonic development, larvae and adults can still survive when DPY-27 is missing. In these worms, all known mechanisms involved in dosage compensation are disrupted and the X is no longer repressed. Our results suggest that the maintenance of dosage compensation in nematodes is an active process, and that it is essential for survival when the organism is developing, but once fully developed, the process becomes dispensable. -
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Abstract Background The increase in DNA copy number in Down syndrome (DS; caused by trisomy 21) has led to the DNA dosage hypothesis, which posits that the level of gene expression is proportional to the gene’s DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.0×). In contrast, other reports suggest that dosage compensation is not a common mechanism of gene regulation in trisomy 21, providing support to the DNA dosage hypothesis.
Results In our work, we use both simulated and real data to dissect the elements of differential expression analysis that can lead to the appearance of dosage compensation, even when compensation is demonstrably absent. Using lymphoblastoid cell lines derived from a family with an individual with Down syndrome, we demonstrate that dosage compensation is nearly absent at both nascent transcription (GRO-seq) and steady-state RNA (RNA-seq) levels. Furthermore, we link the limited apparent dosage compensation to expected allelic variation in transcription levels.
Conclusions Transcription dosage compensation does not occur in Down syndrome. Simulated data containing no dosage compensation can appear to have dosage compensation when analyzed via standard methods. Moreover, some chromosome 21 genes that appear to be dosage compensated are consistent with allele specific expression.
