Evolution of histone 2A for chromatin compaction in eukaryotes

There are up to three meters of DNA in a human cell. To fit this length into the cell's nucleus in an organized manner, DNA is wrapped around proteins called histones and then tightly packaged to form a structure called chromatin. The interaction between the histones and the DNA is helped by certain amino acids on the surface of the histones fitting snugly into the DNA molecule. Plants and animals have genomes that are significantly larger than those of single-celled organisms. However, although genome size has increased gradually during the evolution of complex organisms, the size of the nucleus has not undergone a similar expansion. Large genomes are therefore packaged more tightly than small genomes. However, we do not fully understand how different species evolved the ability to do this. Now Macadangdang, Oberai, Spektor et al. have compared the histones of 160 species ranging from single-celled microorganisms to plants and animals. This revealed that the amino acids in a particular type of histone—histone 2A—vary according to genome size. Organisms with small genomes use histone 2A proteins with fewer arginine amino acids on their surface than organisms with large genomes. Further experiments showed that yeast cells engineered to contain arginine-rich histones wind their DNA more tightly; and, in some cases when the chromatin was more compacted, the nuclei were also smaller. On the other hand, removing arginines from histones in human cells cause the chromatin to be loosely packed and the nuclei to be larger than normal. Moreover, chromatin is often abnormally packed in cancer cells and Macadangdang et al. found that many of these cells contained histones with fewer arginines than normal. Plants, animals, and other eukaryotes have evolved a variety of mechanisms to control how much they compact their chromatin in addition to the way discovered by Macadangdang et al. Future work is now needed to determine how these different mechanisms work together in different species such that the chromatin is compacted to the optimal level.