Case 1: What was the first nucleic acid molecule, and how did it arise?

CASE 1 The First Cell: Life’s Origins

RNA is a remarkable molecule. Like DNA, it can store information in its sequence of nucleotides. In addition, some RNA molecules can actually act as enzymes that facilitate chemical reactions. Because RNA has properties of both DNA (information storage) and proteins (enzymes), many scientists think that RNA, not DNA, was the original information-storage molecule in the earliest forms of life on Earth. This idea, sometimes called the RNA world hypothesis, is supported by other evidence as well. Notably, as we will see, RNA is involved in key cellular processes, including DNA replication, transcription, and translation. Many scientists believe that this involvement is a remnant of a time when RNA played a more central role in life’s fundamental processes.

Ingenious experiments carried out by Jack W. Szostak and collaborators show how RNA could have evolved the ability to catalyze a simple reaction. A strand of RNA was synthesized in the laboratory and then replicated many times to produce a large population of identical RNA molecules. Next, the RNA was exposed to a chemical that induced random changes in the identity of some of the nucleotides in these molecules. These random changes were mutations that created a population of diverse RNA molecules, much in the way that mutation builds genetic variation in cells.

Next, all of these RNA molecules were placed into a container, and those RNA variants that successfully catalyzed a simple reaction—cleaving a strand of RNA, for example, or joining two strands together—were isolated, and the cycle was repeated. In each round of the experiment, the RNA molecules that functioned best were retained, replicated, subjected to treatments that induced additional mutations, and then tested for the ability to catalyze the same reaction. With each generation, the RNA catalyzed the reaction more efficiently, and after only a few dozen rounds of the procedure, very efficient RNA catalysts had evolved. Experiments such as this one suggest that RNA molecules can evolve over time and act as catalysts. Therefore, many scientists believe that RNA, with its dual functions of information storage and catalysis, was a key molecule in the very first forms of life.

If RNA played a key role in the origin of life, why do cells now use DNA for information storage and proteins to carry out other cellular processes? RNA is much less stable than DNA, and proteins are more versatile, so a plausible explanation is that life evolved from an RNA-based world to one in which DNA, RNA, and proteins are specialized for different functions.