Dosage compensation

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

Dosage Compensation and Effect for RNA Synthesis in Chromosome Puffs of Drosophila melanogaster

Abstract: SEX linked genes are usually expressed equally in both sexes of Drosophila, although they are present as a single dose in males and a double dose in females. This is known as dosage compensation1, a term also used when abnormal increases or decreases of gene doses are compensated. If phenotypic expression deviates from dosage compensation towards an effect proportional to the gene dose2 the term “dosage effect” is used.

Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4

Abstract: Background: Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2) is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17b-hydroxysteroid dehydrogenase type 4 (HSD17B4), an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ) and females (ZW) because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. Results: Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. Conclusions: Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.

Dosage compensation of the period gene in Drosophila melanogaster.

Abstract: The period (per) gene is located on the X chromosome of Drosophila melanogaster. Its expression influences biological clocks in this fruit fly, including the one that subserves circadian rhythms of locomotor activity. Like most X-linked genes in Drosophila, per is under the regulatory control of gene dosage compensation. In this study, we assessed the activity of altered or augmented per+ DNA fragments in transformants. Relative expression levels in male and female adults were inferred from periodicities associated with locomotor behavioral rhythms, and by histochemically assessing beta-galactosidase levels in transgenics carrying different kinds of per-lacZ fusion genes. The results suggest that per contains multipartite regulatory information for dosage compensation within the large first intron and also within the 3' half of this genetic locus.

Red cell glucose-6-phosphate dehydrogenase activity in individuals with abnormal numbers of X-chromosomes

Abstract: SUMMARY Red cell glucose-6-phosphate dehydrogenase (G-6-PD) activity was measured in fourteen XXX, eleven XX Y, three XO individuals, four individuals who were 17 but had testicular feminization, and in appropriate male and female controls. No evidence for any quantitative relationship between the number of X-chromosomes present and the level of red-cell G-6-PD activity was observed. Since G-6-PD is known to be determined by at least one gene locus in the X-chromosome, these results in agreement with others imply complete dosage compensation. In thirteen patients with thyrotoxicosis a significant elevation of the mean level of red cell G-6-PD was demonstrated, indicating that such increases could be detected under the general conditions of the investigation. The results are discussed in terms of various hypotheses accounting for dosage compensation.