Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.

Genetic control of X inactivation and processes leading to X-inactivation skewing.

Abstract: The chromosomal basis of sex determination (i.e., XX in females, XY in males) results in an inequality of gene copy number and content between males and females. In humans (and other mammals) the potential imbalance of gene expression from the two X chromosomes in females is resolved by inactivating one X in all the somatic tissues. Beginning in the late blastocyst stage of embryonic development, one of the two X chromosomes is globally down-regulated in each somatic cell, resulting in expression from only one allele at the vast majority of X-encoded loci. While the paternal X is selectively inactive in the extraembryonic tissues (vide infra), in the embryo proper the process of X inactivation is random between the maternal and paternal X chromosomes. The result is that most females have mosaic expression of maternal and paternal alleles of X chromosome loci. The mean contribution from each chromosome is 50%, but because the process is generally random, a normal female may vary considerably from the mean. 67 refs., 1 fig.

A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated

Abstract: Mammalian X and Y chromosomes evolved from an autosomal pair; the X retained and the Y gradually lost most ancestral genes1,2. In females, one X chromosome is silenced by X inactivation, a process that is often assumed to have evolved on a broadly regional or chromosomal basis3. Here we propose that genes or clusters common to both the X and Y chromosomes (X–Y genes) evolved independently along a multistep path, eventually acquiring dosage compensation on the X chromosome. Three genes studied here, and other extant genes, appear to be intermediates. ZFX, RPS4 and SMC were monitored for X inactivation in diverse species by assaying CpG-island methylation, which mirrors X inactivation in many eutherians. ZF evidently escaped X inactivation in proto-eutherians, which also possessed a very similar Y-linked gene; both characteristics were retained in most extant orders, but not in myomorph rodents. For RPS4, escape from X inactivation seems unique to primates. SMC escapes inactivation in primates and myomorphs but not in several other lineages. Thus, X inactivation can evolve independently for each of these genes. We propose that it is an adaptation to the decay of a homologous, Y-linked gene.

Replication‐associated gene dosage effects shape the genomes of fast‐growing bacteria but only for transcription and translation genes

Abstract: The bidirectional replication of bacterial genomes leads to transient gene dosage effects. Here, we show that such effects shape the chromosome organisation of fast-growing bacteria and that they correlate strongly with maximal growth rate. Surprisingly the predicted maximal number of replication rounds shows little if any phylogenetic inertia, suggesting that it is a very labile trait. Yet, a combination of theoretical and statistical analyses predicts that dozens of replication forks may be simultaneously present in the cells of certain species. This suggests a strikingly efficient management of the replication apparatus, of replication fork arrests and of chromosome segregation in such cells. Gene dosage effects strongly constrain the position of genes involved in translation and transcription, but not other highly expressed genes. The relative proximity of the former genes to the origin of replication follows the regulatory dependencies observed under exponential growth, as the bias is stronger for RNA polymerase, then rDNA, then ribosomal proteins and tDNA. Within tDNAs we find that only the positions of the previously proposed 'ubiquitous' tRNA, which translate the most frequent codons in highly expressed genes, show strong signs of selection for gene dosage effects. Finally, we provide evidence for selection acting upon genome organisation to take advantage of gene dosage effects by identifying a positive correlation between genome stability and the number of simultaneous replication rounds. We also show that gene dosage effects can explain the over-representation of highly expressed genes in the largest replichore of genomes containing more than one chromosome. Together, these results demonstrate that replication-associated gene dosage is an important determinant of chromosome organisation and dynamics, especially among fast-growing bacteria.

Dosage compensation of the sex chromosomes

Abstract: Differentiated sex chromosomes evolved because of suppressed recombination once sex became genetically controlled In XX/XY and ZZ/ZW systems, the heterogametic sex became partially aneuploid after degeneration of the Y or W Often, aneuploidy causes abnormal levels of gene expression throughout the entire genome Dosage compensation mechanisms evolved to restore balanced expression of the genome These mechanisms include upregulation of the heterogametic chromosome as well as repression in the homogametic sex Remarkably, strategies for dosage compensation differ between species In organisms where more is known about molecular mechanisms of dosage compensation, specific protein complexes containing noncoding RNAs are targeted to the X chromosome In addition, the dosage-regulated chromosome often occupies a specific nuclear compartment Some genes escape dosage compensation, potentially resulting in sex-specific differences in gene expression This review focuses on dosage compensation in mammals, with comparisons to fruit flies, nematodes, and birds