Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University
Every sexually reproducing organism has some autosomes and sex chromosomes. The sex chromosomes determine the sex of the organism. In the pair of sex chromosomes, one chromosome comes from the father while the other chromosome comes from the mother. While the number of autosomes remains the same, the number of the X chromosome is different in males and females. This makes adjustment of the somatic expression of X-linked genes mandatory so that both males and females produce the same level of proteins encoded by genes present on the X chromosome.
Transcription of the X-linked genes is adjusted to compensate for the differing number of X chromosomes, this phenomenon is known as dosage compensation. The strategy for dosage compensation varies across the animal kingdom, some to increase chromosome X transcription in males, others to randomly inactivate one X or partially suppress both X chromosomes in females. To understand gene expression and its role in development the understanding of the spatial and temporal patterns of dosage compensation is crucial. ScRNA-seq is used to study dosage compensation.
More about dosage compensation
Extensive studies on dosage compensation have been done on drosophila somatic tissues (brain) in the past. However, the role of dosage compensation in germ cells (testis) and its role in spermatogenesis is not yet known. Prior studies have shown the possibility of germline dosage compensation however to what extent and its timing is not fully understood. At the time of meiosis in a male germ cell (spermatocyte) the sex chromosomes are epigenetically silenced becoming inaccessible to the cell’s transcriptional machinery. This is called Meiotic Sex Chromosome Inactivation (MSCI).
The occurrence of MSCI is widespread and fairly conserved in many organisms. However previous studies have shown that both dosage compensation and MSCI are absent in drosophila. In germ cells, the maleless (MLE) protein in drosophila does not associate with the X chromosome unlike in somatic cells. This suggests an alternative role of MLE in germ cells. The male sex lethal (MSL) protein that regulates dosage compensation does not localize to the male germline X chromosome. So, the mechanism of germline dosage compensation in male drosophila continues to be a mystery.
The study
In recent research published in PLOS Genetics, Witt et al. sought to quantify the relative transcriptional dynamics of sex chromosomes and autosomes using high throughput scRNA-sequencing using testis from two different strains of Drosophila melanogaster. The researchers observed dosage compensation in terms of X:autosome count ratio and differential gene activity.
The pre-meiotic cells and somatic cells show X:autosome expression ratios close to 1. However, after meiosis, this ratio declined to around 0.6 to 0.7. According to researchers the X:autosome ratio which is higher early in germ cells than somatic cells are indicative of dosage compensation. The rox1 and rox2 RNAs are the components of the dosage compensation machinery in drosophila. In this study, the researchers found that pre-meiotic dosage compensation occurred despite negligible expression of germline rox1 and rox2. The same was confirmed with RNA-FISH.
What next?
This study strongly supports the presence of germline dosage compensation in drosophila pre-meiotic germ cells. The dosage compensation was found to occur despite the sparse expression of rox1, rox2, and most DCC (dosage compensation complex) proteins. The researchers believe that the germline dosage compensation may be mediated by CLAMP which binds to the MSL CE site and in turn increase the X chromosome accessibility as its expression was observed to be upregulated in early germ cells. Future studies are required to confirm this assumption assert the researchers.
Also read: Importance of Organoid Technology in Cancer Research
Reference:
- Witt E, Shao Z, Hu C, Krause HM, Zhao L (2021) Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis. PLoS Genet 17(8): e1009728. https://doi.org/10.1371/journal.pgen.1009728
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Author info:
Vaishnavi Kardale is a master’s student at the Bioinformatics Centre, Savitribai Phule University. She is interested in protein folding mechanisms and wants to study them further.
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