Researchers at The Wistar Institute, studying the mechanisms that control how the genetic material is managed during gamete production, have now identified a single molecule whose presence is required for genome compaction. Their experiments showed that the molecule "marks" the chromatin just prior to compaction and that its presence is mandatory for successful compaction. Additionally, after first noting the molecule's activity during the production of yeast spores, the scientists saw the same activity during the creation of sperm in fruit flies and mice, suggesting that the mechanisms governing genome compaction are evolutionarily ancient, highly conserved in species whose lineages diverged long ago. A report on the new study appears in the September 15 issue of Genes & Development. A "Perspectives" review in the same issue expands on the significance of the findings.
"This molecular mark is required at a critical time leading up to genome compaction in spores and sperm," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. "Also, there seems to be a similarity in the way the mark is used in organisms as different from each other as yeast and mammals, suggesting that compaction has been important throughout evolution."
Berger speculates that compaction might answer a nu mber of important biological purposes.
"During the time the DNA is single-stranded, as it is in the gametes, it's much more susceptible to breaks and mutations," she says. "Compaction may keep the genome resistant to damage of all kinds. This is critical ?if the single-stranded DNA in gametes breaks, it can fall apart and possibly reassemble itself in devastating translocations."
She notes that normal double-stranded DNA, on the other hand, has the ability to repair breaks in one of its single strands by using the chemical bases in the companion strand as a reference. Bases in DNA pair only in predetermined combinations, so that one strand can serve as a template for the other.
"Compaction might also affect sperm fertility and function in the higher organisms, and thus the propagation of the species," says Thanuja Krishnamoorthy, Ph.D., lead author on the study. "It's vital that we better understand genome compaction during the production of mature sperm."
The molecule in question is a phosphorous molecule that modifies a histone. Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, the substructure of chromosomes.
To test the team's observations, Krishnamoorthy performed an experiment in yeast in which she altered the histone's chemical composition at a single point, the point at which the molecule attaches to, or marks, the histone. The results were clear and compelling: With the alteration, the molecule was unable to attach to the histone, and compaction was severely limited.
"We saw a significant increase in genomic volume in the resulting yeast spores, as though the compaction had been lost," Berger says. "The frequency of successful spore creation was also lowered significantly."