Image: Lancelet
Carol MacKintosh
An amphioxus (also called a lancelet), which is a very distant cousin to humans and other vertebrates. It is the creature most similar to the original spineless organism that existed before a major genomic event occurred.
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updated 7/24/2012 8:08:41 PM ET 2012-07-25T00:08:41

Over 500 million years ago a spineless creature on the ocean floor experienced two successive doublings in the amount of its DNA, a "mistake" that eventually triggered the evolution of humans and many other animals, says a new study.

The good news is that these ancient DNA doublings boosted cellular communication systems, so that our body cells are now better at integrating information than even the smartest smartphones. The bad part is that communication breakdowns, traced back to the very same genome duplications of the Cambrian Period, can cause diabetes, cancer and neurological disorders.

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"Organisms that reproduce sexually usually have two copies of their entire genome, one inherited from each of the two parents," co-author Carol MacKintosh explained to Discovery News. "What happened over 500 million years ago is that this process 'went wrong' in an invertebrate animal, which somehow inherited twice the usual number of genes. In a later generation, the fault recurred, doubling the number of copies of each gene once again."

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MacKintosh, a professor in the College of Life Sciences at the University of Dundee, said that such duplications also happened in plant evolution. As for the progeny of the newly formed animal, they remarkably survived and thrived.

"The duplications were not stable, however, and most of the resulting gene duplicates were lost quickly — long before humans evolved," she continued. But some did survive, as MacKintosh and her team discovered.

Her research group studies a network of several hundred proteins that work inside human cells to coordinate their responses to growth factors and to insulin, a hormone. Key proteins involved in this process are called 14-3-3.

For this latest study, the scientists mapped, classified and conducted a biochemical analysis of the proteins. This found that they date back to the genome duplications, which occurred during the Cambrian.

The first animal to carry them remains unknown, but gene sequencing shows that a modern day invertebrate known as amphioxus "is most similar to the original spineless creature before the two rounds of whole genome duplication," MacKintosh said. "Amphioxus can therefore be regarded as a ‘very distant cousin’ to all the vertebrate (backboned) species."

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The inherited proteins appear to have evolved to make a "team" that can tune into more growth factor instructions than would be possible with a single protein.

"These systems inside human cells therefore behave like the signal multiplexing systems that enable our smartphones to pick up multiple messages," MacKintosh shared.

The teamwork may not always be a good thing, though. The researchers propose that if a critical function were performed by a single protein, as in amphioxus, then its loss or mutation would likely be lethal, resulting in no disease.

If multiple proteins are working as a team, however, and one or more becomes lost or mutated, the individual may survive, but could still wind up with a debilitating disorder. Such breakdowns could help to explain how diseases, such as diabetes and cancer, are so entrenched in humans.

"In type 2 diabetes, muscle cells lose their ability to absorb sugars in response to insulin," MacKintosh said. "In contrast, greedy cancer cells don't await instructions, but scavenge nutrients and grow out of control."

Chris Marshall, a professor of cell biology at the Institute of Cancer Research at Royal Cancer Hospital, told Discovery News that he thinks the research "gives new insights into the evolution of signaling mechanisms that control cell behavior."

MacKintosh and her team are now focusing on the protein families whose upset causes melanoma and neurological disorders. Because of the likely connection to ancient genetic events, the research could shed light on human and other animal evolution while also helping to unravel diseases.

© 2012 Discovery Channel

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