Dosage sensitivity of X-linked genes in human embryonic single cells.
BMC Genomics
; 20(1): 42, 2019 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-30642250
ABSTRACT
BACKGROUND:
During the evolution of mammalian sex chromosomes, the degeneration of Y-linked homologs has led to a dosage imbalance between X-linked and autosomal genes. The evolutionary resolution to such dosage imbalance, as hypothesized by Susumu Ohno fifty years ago, should be doubling the expression of X-linked genes. Recent studies have nevertheless shown that the X to autosome expression ratio equals ~ 1 in haploid human parthenogenetic embryonic stem (pES) cells and ~ 0.5 in diploid pES cells, suggesting no doubled expression for X-linked genes and refuting Ohno's hypothesis.RESULTS:
Here, by reanalyzing an RNA-seq-based single-cell transcriptome dataset of human embryos, we found that from the 8-cell stage until the time-point just prior to implantation, the expression levels of X-linked genes are not two-fold upregulated in male cells and gradually decrease from two-fold in female cells. Additional analyses of gene expression noise further suggest that the dosage sensitivity of X-linked genes is weaker than that of autosomal genes in differentiated female cells, which contradicts a key assumption in Ohno's hypothesis, that most X-linked genes are dosage sensitive. Moreover, the dosage-sensitive housekeeping genes are preferentially located on autosomes, implying selection against X-linkage for dosage-sensitive genes.CONCLUSIONS:
We observed dosage imbalance between X-linked and autosomal genes, as well as relatively high expression noise from X-linked genes. These results collectively suggest that X-linked genes are less dosage sensitive than autosomal genes, putting one primary assumption of Ohno's hypothesis in question.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mecanismo Genético de Compensação de Dose
/
Genes Ligados ao Cromossomo X
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
BMC Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China