Dosage compensation

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

[Structural heterochromatin and X-chromosome inactivation].

Abstract: Our previous studies on the expression of the G6PD and alpha-GAL genes from the X chromosome of inter-specific hybrids of voles of the Microtus genus have demonstrated an unusual pattern of X-inactivation in the parents. The observed phenomenon was explained as the presumable result of nonrandom inactivation of the X chromosomes with a heterochromatin block in crosses involving Microtus arvalis whose X lacks a heterochromatin region and also of random X inactivation when both parents had heterochromatin blocks on the Xs. Based on known models, we discuss here the possible mechanisms of the effect of heterochromatin on X-inactivation; we give preference to the model postulating binding of nonhistone protein to the inactivation centre as the key event. The hypothesis we offer suggests change in chromatin conformation in the inactivation centre during packaging of heterochromatic region of a chromosome; the protein molecules diffusing along the chromosome towards the heterochromatin region by the "facilitated diffusion" mechanism may happen to be in the region of the X-inactivation centre, which, being in a favorable state, binds specifically to it; as a consequence, the binding probability of protein to heterochromatin increases as compared to chromosome without heterochromatin block.

Concurrent X chromosome inactivation and upregulation during non-human primate preimplantation development revealed by single-cell RNA-sequencing.

Abstract: In mammals, dosage compensation of X-linked gene expression between males and females is achieved by inactivation of a single X chromosome in females, while upregulation of the single active X in males and females leads to X:autosome dosage balance. Studies in human embryos revealed that random X chromosome inactivation starts at the preimplantation stage and is not complete by day 12 of development. Alternatively, others proposed that dosage compensation in human preimplantation embryos is achieved by dampening expression from the two X chromosomes in females. Here, we characterize X-linked dosage compensation in another primate, the marmoset (Callithrix jacchus). Analyzing scRNA-seq data from preimplantation embryos, we detected upregulation of XIST at the morula stage, where female embryos presented a significantly higher expression of XIST than males. Moreover, we show an increase of X-linked monoallelically expressed genes in female embryos between the morula and late blastocyst stages, indicative of XCI. Nevertheless, dosage compensation was not achieved by the late blastocyst stage. Finally, we show that X:autosome dosage compensation is achieved at the 8-cell stage, and demonstrate that X chromosome dampening in females does not take place in the marmoset. Our work contributes to the elucidation of primate X-linked dosage compensation.

Acceleration of X-chromosome gene order evolution in the cattle lineage

Abstract: The gene order on the X chromosome of eutherians is generally highly conserved, although an increase in the rate of rearrangement has been reported in the rodent lineage. Conservation of the X chromosome is thought to be caused by selection related to maintenance of dosage compensation. However, we herein reveal that the cattle (Btau4.0) lineage has experienced a strong increase in the rate of X-chromosome rearrangement, much stronger than that previously reported for rodents. We also show that this increase is not matched by a similar increase on the autosomes and cannot be explained by assembly errors. Furthermore, we compared the difference in two cattle genome assemblies: Btau4.0 and Btau6.0 (Bos taurus UMD3.1). The results showed a discrepancy between Btau4.0 and Btau6.0 cattle assembly version data, and we believe that Btau6.0 cattle assembly version data are not more reliable than Btau4.0.

Avian Genome Evolution - Gene Expression, Gene Divergence and Sexual Dimorphism

Abstract: This study has focused on: (i) differences in how males and females use the genes in the genome, (ii) how sex chromosomes evolve and (iii) how the evolutionary rate of genes are affected by the chromosome on which they are located on and the gene expression level they experience. A large-scale microarray was developed for the zebra finch, Taeniopygia guttata and techniques were developed so that this microarray could also be used for wild passerine birds. Results from this thesis show that sexual dimorphism in gene expression is extensive in the brain of birds and that most genes involved in this sexual dimorphism is expressed at higher levels in males than in females and are located on the sex chromosome called the Z chromosome. Results further indicate that female birds dosage compensate to quite a high extent, a fact that has been questioned in recent studies. Dosage compensation is the process by which the sex with only one Z chromosome achieves gene expression on Z-linked genes that is balanced with gene expression from autosomal chromosomes, which are all present in the genome in two copies. Moreover, results from this study show that dosage compensation is more likely to be achieved for genes with low expression levels than for highly expressed genes on the Z chromosome. Furthermore, we have demonstrated that genes on the Z chromosome have very high evolutionary rates between species and that genes on large autosomal chromosomes evolve at a higher pace than on small chromosomes. We also find that genes with low gene expression levels evolve faster than other genes in the genome and results indicate that genes with medium high gene expression are the most conserved in birds. Moreover, genes on the Z chromosome which have higher expression in males than in females, so called male-biased genes, evolve faster than unbiased genes on the Z chromosome. Male-biased Z-linked genes were also shown to evolve at the same rates regardless of their gene expression level, a pattern which was not true for unbiased Z-linked genes or autosomal genes. Lastly, we have also identified a previously un-know sex-chromosome in birds. Gene expression analyses and linkage mapping shows that chromosome 4a, a regular autosome in the zebra finch, has become a neo-sex chromosome in warblers (Sylviidae). Our results indicate that the avian Z chromosome is highly likely to have played a large role in speciation and adaptive evolution in birds, and opens up for interesting comparisons with the well-studied sex chromosomes in for example mammals.

The Basic Difference in Constitution between the Mammalian X and the Drosophila X

Abstract: During the course of evolution progressive genetic deterioration occurred to the Y-chromosome. As a result, the Y-chromosome of placental mammals became a highly specialized male-determiner, having but one function namely to induce the indifferent embryonic gonad to develop as testis. The consequence of this specialization by the Y was that almost all of the original Mendelian genes which had been maintained by the X-chromosome, had to accommodate themselves to a hemizygous existence in the heterogametic male sex. The hemizygous existence for all the genes on the X should be very perilous since monosomy for even the smallest autosome (only one-fourth the size of the X) is apparently lethal in man.