Huntingtin gene and its CAG repeats number in Primates

The Hdh gene arose with no CAG (cytosine-adenine-guanine) repeats in Dictyostelium discoideum around 800 million years ago, before the protostome-deuterostome divergence. The CAG then appeared in, and is unique to, the deuterostome branch. Two CAGs are found in Hdh in sea urchin (Strongylocentrotus purpuratus) , the first species to carry a primitive nervous system, and two CAGs are present in amphioxus (Branchiostoma floridae) , the first species to exhibit a rudimental hollow nerve tube and cephalization. Four CAGs are found in Hdh from the more evolved fishes, amphibians and birds. The CAG further expands in mammals and reaches its maximum length in humans. In Homo sapiens the Hdh gene is located in the short arm of chromosome 4 and is characterized by a CAG sequence repeated 9–35 times. Normal subjects have revealed an increase in grey matter with increasing length of the CAG repeat, indicating that CAG size can influence normal brain structure. However, CAG repeats exceeding 35 in number cause Huntington’s disease, a neurodegenerative syndrome that occurs earlier due to a greater number of CAG repeats. Our hypothesis is that the progressive increase in CAG length in the Hdh gene observed during evolution may be implicated in the evolutionary changes that have occurred in developing adult nervous systems throughout vertebrate phylogeny, with a possible role for the CAG in newly emerging cognitive functions in the mammalian brain. We have collected genomic DNA and have begun to amplify the CAG tract from primates (Nycticebus pygmaeus, Eulemur fulvus albifrons, Lemur variegatus, Lemur catta, Sanguinus imperator, Cebus apella, Macaca fuscata, Macaca mulatta, Papio hamadryas, Chlorocebus aethiops, Cercocebus atys, Mandrillus sphinx, Colobus, Hylobates lar, Pongo, Gorilla gorilla, Pan troglodytes) in order to examine the inter- and intraspecific variability. Preliminary results will be shown.