YOU have probably heard of evolution in action – but how about evolution in reverse?
Many of the genes in our bodies have descended from ancient genes that have mutated and changed their function. Petr Tvrdik and Mario Capecchi of the University of Utah, Salt Lake City, have now managed to demonstrate this in mice by recreating an ancient gene from two of its modern descendants.
Half a billion years ago, the size of our ancestor’s genome quadrupled. With four copies of every gene knocking about, genes either had to make themselves useful, or be swiftly dumped. The quadrupling meant that 13 Hox genes, which control the development of body shape, became 52. The ones that didn’t mutate to do something useful were lost, so today mammals have 39 Hox genes.
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Tvrdik and Capecchi focused on two that were originally duplicates but have evolved to perform different functions. Hoxa1 controls brain stem development in the early embryo, while Hoxb1 directs nerve growth in an area of the brain that controls facial expression.
The two genes make the same protein, but in different places in the brain, and at different times. In other words, it is the regulatory region of the gene that differs between Hoxa1 and Hoxb1, not the protein-coding region.
To reconstruct the ancestral Hox1 gene, Tvrdik and Capecchi attached the regulatory sequence from Hoxb1 – which turns the gene on later in fetal development – to the Hoxa1 gene. That way, one gene did the job of two. Mice with the new Hox1 gene, but with their Hoxa1 and Hoxb1 genes knocked out, developed normally (Developmental Cell, DOI: 10.1016/j.devcel.2006.06.016).
“We constructed a gene that is fairly similar to the ancestral Hox1 gene present in the vertebrate lineage half a billion years ago,” says Tvrdik.