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Multi-layer dosage compensation of the avian Z chromosome (single-cell RNA-seq)

ABSTRACT: Multi-layer dosage compensation of the avian Z chromosome (single-cell RNA-seq)

PROVIDER: PRJEB80546 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	ERR13719680_1.fastq.gz	Fastqsanger.gz
	ERR13719680_2.fastq.gz	Fastqsanger.gz

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Multi-layered dosage compensation of the avian Z chromosome

Project description:Sex-chromosome dosage represents a challenge for heterogametic species to maintain correct proportion of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance of X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZW/ZZ system) have been found to lack efficient compensation at RNA level, challenging the necessity of resolving major gene-dosage discrepancies in avian cells. Through allele-resolved multiome analyses, we comprehensively examined dosage compensation in female (ZW), male (ZZ), and rare intersex (ZZW) chicken. Remarkably, this revealed that females exhibit upregulation of their single Z through increased transcriptional burst frequency similar to mammalian X-upregulation, and that Z-protein levels are further balanced via enhanced translation efficiency in females. Global analyses of transcriptional kinetics elements in birds demonstrate remarkable conservation of the genomic encoding of burst kinetics between mammals and birds. Our study uncovers new mechanisms for achieving sex-chromosome dosage compensation and highlights the importance of gene-dosage balance across diverse species.

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A male-essential microRNA is key for avian sex chromosome dosage compensation

Project description:Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ). The differentiation of avian sex chromosomes from ancestral autosomes entailed the loss of most genes from the W chromosome during evolution. However, to what extent mechanisms evolved that counterbalance the consequences of this extensive gene dosage reduction in female birds has remained unclear. Here we report functional in vivo and evolutionary analyses of a Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression that was previously proposed to play a key role in sex chromosome dosage compensation1. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality of homozygous knockout males, likely due to the highly specific upregulation of dosage-sensitive Z-linked target genes of miR-2954. Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution. Altogether, our work unveils a scenario where evolutionary pressures on females following W gene loss led to the evolution of transcriptional upregulation of dosage-sensitive genes on the Z not only in female but also in male birds. The resulting overabundance of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. Our findings demonstrate that birds have evolved a unique sex chromosome dosage compensation system in which a microRNA has become essential for male survival.

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Dosage compensation of Z sex chromosome genes in avian fibroblast cells

Project description:Sex in birds is genetically determined, molecular mechanism of which is not well-understood. Their Z sex chromosome (chrZ) lacks whole chromosome inactivation as known for mammalian chrX. To investigate the extent of chrZ dosage compensation and its role in somatic cell’s sex specification, we used a highly-quantitative method and analyzed transcriptional activities of male and female fibroblasts from seven birds. Our data indicate for the first time that ¾ of chrZ genes are strictly compensated, similar to that observed in chrX. We also describe non-compensated chrZ genes and identify Ribosomal Protein S6 (RPS6) as a candidate for universal, sex-dimorphic genes in birds.

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Project description:Studying X-chromosome dosage compensation dynamics in human early embryos using single cell RNA sequencing

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