7 Jul 2026
Researchers from the Becker Lab show that when the vital regulation of equal gene expression of the sex chromosomes in Drosophila is disabled, cultured cells regain their fitness by reversibly adjusting the numbers of sex chromosomes.
© Becker Lab / LMU
These findings document a rare example of genome evolution under selective pressure.
Evolution’s invention of sexuality has been remarkably successful. The two sexes often differ in their sex chromosomes. In humans and Drosophila fruit flies, females have two X chromosomes, whereas males have only one. The female genome is balanced, but the males must compensate the deficiency of having only one X with a specialised molecular machine, the dosage compensation complex (DCC). This gene regulator boosts the activity of genes on that lone X chromosome. Failure to compensate is fatal.
So it was a surprise when fruit fly cells, stripped of a system that keeps their sex chromosome in balance, simply carried on. The team deleted roX2, the gene for the RNA component the DCC needs to locate the X, in cultured male cells. Without it, the complex could no longer bind the X or upregulate its genes. Strangely, overall gene expression remained balanced.
The cells compensated not by responding to the defect, but by an interesting process of evolutionary selection. Upon DCC loss, cells that had by chance acquired and extra X chromosome through cell division errors retained balanced gene expression. They gradually outgrew the rest and came to dominate the population. In this way gene dosage balance was restored. The change proved reversible. When the researchers restored roX2, an extra X became a disadvantage, and cells carrying it were outcompeted. Within weeks, the population returned to its original chromosome number. The selective pressure for balanced gene expression that had added a chromosome could take it away again.
The findings show how critical balanced X chromosome expression is for cell survival, strict enough to reshape a genome even in these tissue culture cells with sloppy chromosome distribution during cell division. Because the system can be switched off and on, it also provides a unique experimental model for studying how genomes evolve under selective pressure, offering new insights into chromosome biology and cellular adaptation.
Publication: Gkountromichos et al.: Dosage compensation defects due to roX RNA loss are rescued by recalibration of X/autosome stoichiometry. Nucleic Acids Research, 2026