Question

How does \(X\) chromosome dosage compensation in Drosophila differ from that process in humans?

Short answer

Answer: The major differences in X chromosome dosage compensation between Drosophila and humans are the mechanism and the regulating complexes. Drosophila upregulates gene expression on the single X chromosome in males through the Male-Specific Lethal (MSL) complex, while humans equalize expression using X-inactivation in female cells, regulated by the long non-coding RNA Xist.

Step-by-step solution

Understand dosage compensation

Dosage compensation is the process by which organisms balance the expression of genes on the sex chromosomes (X and Y) in males and females. In organisms with sex chromosome systems like humans and Drosophila, males have one X and one Y chromosome, while females have two X chromosomes. To ensure equal gene expression levels between sexes, dosage compensation mechanisms have evolved to equalize X-linked gene expression between males and females.

Dosage compensation in Drosophila

In Drosophila, dosage compensation is achieved by upregulating the expression of the single X chromosome in males to reach the same levels as in females with two X chromosomes. The Male-Specific Lethal (MSL) complex, a group of proteins and non-coding RNAs, is responsible for this upregulation. The MSL complex specifically binds to the male X chromosome, modifying its chromatin structure, and consequently enhancing transcription of the X-linked genes.

Dosage compensation in humans

In humans, dosage compensation is primarily accomplished by the process of X-inactivation. X-inactivation results in the inactivation of one of the two X chromosomes in female cells, equalizing gene expression levels between males and females. The inactivated X chromosome forms a condensed structure called a Barr body, which prevents transcription of its genes. This process is regulated by a long non-coding RNA called Xist, which coats the inactivated X chromosome and initiates the formation of the Barr body.

Major differences between Drosophila and humans

There are two key differences in the processes of X chromosome dosage compensation between Drosophila and humans: 1. The mechanism: Drosophila upregulates gene expression on the single X chromosome in males to equalize expression with females, while humans inactivate one of the X chromosomes in female cells via X-inactivation. 2. The regulating complexes: Drosophila dosage compensation is mediated by the MSL complex, which binds to and modifies the male X chromosome to enable gene upregulation. In humans, the process is regulated by the long non-coding RNA Xist, which initiates the inactivation of one X chromosome in females by coating it and leading to the formation of a Barr body.

Key concepts

X-inactivation

X-inactivation is a critical process in mammals that enables effective dosage compensation. Without it, females having two X chromosomes would produce double the amount of X-linked gene products compared to males, who have one X and one Y chromosome. The solution? Silence one of the X chromosomes to balance the scale.

Every cell in a female randomly inactivates one X chromosome during early embryonic development. This inactivation is permanent; the same X chromosome remains inactive in all progeny of each cell. The hero of this process is the Xist RNA, a long non-coding RNA produced by the X chromosome slated for inactivation. Xist RNA coats the chromosome, initiating a cascade of molecular events that lead to its DNA being packaged tightly, forming what’s known as a Barr body. As a result, genes on the inactivated X are effectively turned off.

• Initiation by Xist RNA
• Random inactivation of one X chromosome in females
• Formation of Barr body

Male-Specific Lethal (MSL) complex

In Drosophila, dosage compensation is a fascinating orchestration managed by the Male-Specific Lethal (MSL) complex. Unlike mammals, where one X chromosome is inactivated, Drosophila males increase the expression of genes on their single X chromosome through a process called upregulation.

The MSL complex, an assembly of proteins and non-coding RNAs, rallies to the X chromosome in males. It modifies the chromatin (the material chromosomes are made of) to make it more accessible for transcription. This accessibility encourages the transcriptional machinery to express the X-linked genes at higher levels, thereby ensuring that male Drosophila produce levels of X-linked gene products comparable to their female counterparts.

• Composed of proteins and non-coding RNAs
• Binds to the male X chromosome
• Enhances transcription via chromatin modification

Barr body

A Barr body is the physical manifestation of an inactivated X chromosome in female cells. Identified as a dense, dark-staining spot found in the nucleus, the Barr body is a hallmark feature of cells that have achieved dosage compensation in mammals.

The formation of a Barr body begins when X-inactivation is initiated by the Xist RNA, which spreads across the prospective Barr body chromosome. As the chromosome condenses, regions of its DNA become inaccessible, shutting down gene expression. The presence of the Barr body thus ensures that females do not overexpress X-linked genes relative to males. Each cell nucleus in a typical female has one Barr body, effectively balancing the gene dosage between the sexes.

• Result of X chromosome inactivation
• Visible as a dark spot in the cell nucleus
• Ensures equal gene expression as males