One of the most pressing quests for molecular biologists is to understand the functioning of centromeres, the regions of DNA that hold together the two branches of chromosomes and that play a key role in cell duplication. New information has emerged from a study on zebras by scientists at the University of Pavia, that shows that centromeres do not really need to look like human ones to fulfil their function.
The team, led by Elena Giulotto and Solomon Nergadze, has been using members of the Equus family such as horses, asses, and zebras, as model organisms to study chromosomes. Equids are a good model because they have a fast rate of chromosome evolution and a much simpler centromeric structure than other mammals. The Pavia group had previously found that, unlike in humans and many other species, some chromosomes in horses and donkeys lack satellite DNA, made of short DNA sequences repeated many times, in their centromeric region.
The new study, published in Molecular Biology and Evolution, adds the zebra chromosomes to the picture1. A molecular analyses of skin cells of two species of zebras (Equus burchelli and Equus grevyi) revealed that most of their chromosomes have their centromeres in the middle and are free from satellite DNA. By comparing zebras and horses, that are considered closer to the ancestor of all equid species, the researchers concluded that the chromosomes of zebras derived from the fusion of previous ones during evolution. “We can guess that the ancestor species had many more chromosomes, all with centromeres on one end and with satellite DNA,” says Giulotto.
The researchers also described a new mechanism for forming satellite-free centromeres. When two chromosomes fuse (a phenomenon known as Robertsonian fusion), the centromeric function shifts away from a region of satellite DNA and moves to a new, satellite-free position. The new results confirm that other genetic and epigenetic factors, beyond position and satellite DNA, determine the centromere's function.
“This group is bringing revolutionary knowledge to the field,” says Terje Raudsepp, a geneticist at Texas A&M University, who was not involved in the study. “They are getting to the essence of the dynamic of centromeres, dissecting what is functionally important.”
In humans, chromosomal fusion and rearrangements can lead to cancer and other diseases. Comparing centromeres with and without satellite DNA ,and understanding the biology of centromeres in equids can inform about molecular dysfunctions in human diseases. “We are currently basing our knowledge on a few species, and we are missing important pieces of the puzzle,” says Giulotto.
“This paper presents a natural experiment undertaken with the evolution of zebras, which broadens our understanding of the components that interact to segregate the chromosome”, adds Oliver Ryder, a Professor at the University of California at San Diego.