Genes come and go in our quadrupled genomes

It was recently confirmed that human genes were originally quadrupled, something that occurred before the emergence of vertebrates with jaws.  Careful mapping of several gene families now shows that since then the human evolutionary line has lost many genes that still occur in other animal groups. Certain groups of vertebrates that have doubled their genes on further occasions therefore have more genes than humans do.

As early as 1993 Uppsala researcher Lars G. Lundin found that several chromosome segments in human genes evince noticeable similarities with each other. This indicated that our genome had expanded by copying huge gene regions. Since then careful analyses of gene families have yielded ever stronger support for notion that the entire genome having been doubled twice prior to the emergence of the first vertebrates with jaws, some 450 million years ago. Last summer this hypothesis received more support when the genes of a close relation to vertebrates, the small lancet fish, were published in the journal Nature.

A research team directed by Dan Larhammar has published six articles in 2008 containing painstaking comparisons of gene families and chromosome regions in several different vertebrates, including humans, dogs, chickens, several species of bony fishes, and a shark.

“"The comparison shows that the chromosome regions are surprisingly similar to each other despite the enormous span of time that has passed since the mammalian and bony fish animals groups parted ways in evolution",” says Dan Larhammar.

The gene family that has been studied most closely creates peptides (signal molecules) that are involved in the regulation of appetite. One of these peptides is called NPY and leads to hunger while two related peptides that exist in mammals lead to satiety. In humans these peptides achieve their effect via four different receptors. The latest report from the research team now confirms that the original vertebrates had as many as seven receptors. In the course of evolution nearly half of the receptors were thus lost in the evolutionary line leading to humans.

“"The new study shows that sharks still have all seven original receptors",” says Dan Larhammar.

The researchers describe the loss of genes also for many other gene families that lie in the same chromosome regions as the appetite genes. On the other hand, genes have been added in the various animal groups, especially dramatically in the very bony fishes whose predecessors quadrupled the genes once again about 350 million years ago. Bony fishes therefore have more genes than humans do.

“We show that in certain respects humans have lost genetic complexity and that in some respects other species are genetically considerably more complex than humans. These studies help explain how genes function and how new and more specialized functions arose through evolution.”

Several of the studies were carried out in collaboration with a research team in Singapore. The articles were published in BMC Evolutionary Biology (2 articles), Genomics, Gene, and General and Comparative Endocrinology.  Recently Dan Larhammar’s research team described how the four receptors for opioid peptides (and for morphine) arose in the same way, with chromosome copying 450 million years ago, which was then published in the Proceedings of the American Academy of Sciences PNAS, see press release.

Läs artiklarna; i Evolutionary Biology, nästa i Evolutionary Biology, Genomics, Gene, General and Comparative Endocrinology och PNAS.

For more information please contact Dan Larhammar, phone: +46 (0)18-471 4173, e-mail: Dan.Larhammar@neuro.uu.se