Study offers insights into evolutionary origins of life

IN SOME of the strongest evidence yet to support the RNA world - an era in early evolution when life forms depended on RNA - scientists at the Whitehead Institute for Biomedical Research have created an RNA catalyst, or a ribozyme, that possesses some of the key properties needed to sustain life in such a world.

The new ribozyme, generated by David Bartel and his colleagues at the Whitehead, can carry out a remarkably complicated and challenging reaction, especially given that it was not isolated from nature but created from scratch in the laboratory. This ribozyme can use information from a template RNA to make a third, new RNA. It can do so with more than 95 percent accuracy, and most importantly, its ability is not restricted by the length or the exact sequence of letters in the original template. The ribozyme can extend an RNA strand, adding up to 14 nucleotides, or letters, to make up more than a complete turn of an RNA helix.

These results, described in a recent issue of Science, suggest that RNA could have had the ability to replicate itself and sustain life in early evolution, before the advent of DNA and proteins. The findings will ultimately help evolutionary biologists address questions about how life began on earth more than three billion years ago.

Until almost two decades ago, many researchers thought that RNA was nothing more than a molecular interpreter that helps translate DNA codes into proteins. Then scientists discovered that not all enzymes were proteins - some were made of RNA. Over the past decade, they have developed techniques for producing new ribozymes in the lab, and a series of studies by the Bartel lab at the Whitehead has been lending credence to the notion of an RNA world. Still, none of the ribozymes generated by the Bartel lab or others in the field possessed the sophisticated properties needed to accurately replicate RNA. "Creating a complimentary strand of RNA is a challenging enzymatic reaction because it requires several things to happen at the same time. The reaction must be accurate in incorporating nucleotides based on the template strand, general enough that any template can be copied, and efficient enough to add on a large number of nucleotides," says Wendy Johnston, first author on the paper and research associate in the Bartel lab.

Theories about life's origins

Theories about the origins of life have long intrigued scientists and lay people alike. "A fundamental question about the origin of life is what class of molecules gave rise to some of the earliest life forms?" says Bartel.

For years, scientists debated this question, some arguing that RNA molecules were the progenitors and others arguing in favor of proteins. "It was a classic chicken-and-egg argument. RNA, like DNA, has the genetic information necessary to reproduce but needs proteins to catalyze the reaction. Conversely, proteins can catalyze reactions but cannot reproduce without the information supplied by RNA," says Bartel.

The discovery in 1982 of ribozymes bolstered the notion that RNA came before proteins, but more challenges lay ahead for evolutionary biologists before they could espouse the RNA worldview. For one, there are only eight known ribozymes in nature - nowhere near enough to sustain the range of reactions in an RNA world. Furthermore, compared to protein enzymes, ribozymes seemed slow and inefficient as catalysts. So scientists set out to make artificial ribozymes that were more versatile and efficient than the natural ones. If they could create such ribozymes in the lab, it would suggest that natural ones could have existed during the RNA era, but have become extinct since.

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