Capecchi says that by combining parts of both Hoxa1 and Hoxb1, he and Tvrdik reversed evolution.
"What we have done is essentially go back in time to when Hox1 did what Hoxa1 and Hoxb1 do today," he says. "It gives a real example of how evolution works because we can reverse it."
The hybrid Hoxa1-Hoxb1 gene is not fully identical to the half-billion-year-old Hox1 because it lacks Hoxc1 and Hoxd1. But Hoxc1 vanished during evolution because it was redundant, and Hoxd1 plays a minor role. So the combined Hoxa1-Hoxb1 gene performs essentially all the functions of the ancient gene, Capecchi says.
A New Approach to Gene Therapy?
Capecchi says scientists hypothesized that when a gene duplicates into identical genes, mutations can occur so the once-identical duplicates evolve to split the original job ?a process is called subfunctionalization.
"We are giving an example of how it actually happened ?what elements are involved and how you initially separate the functions, and how can you reconstruct the [ancient] gene to put the functions back again," Capecchi says.
The study raises the prospect of a new approach to gene therapy, Tvrdik says.
If a gene duplicated into two and they evolved separate functions in the body ?for example, one gene works in the liver and the other in the brain ?then "if the brain version of the gene becomes mutated or deleted [to cause a disease] and its gene replacement is difficult or impractical, then our work shows that the 'liver copy' potentially could be recruited to do the brain functions," Tvrdik says.
In other words, regulatory elements from the brain gene might be inserted into the liver gene to reconstruct a gene similar to the normal brain gene.
Source:University of Utah Health Sciences Center