The Search for an RNA "Eve"

The Search for an RNA "Eve," a hypothetical ancestor of some or all of the types of RNA now known, might be possible using a technique pioneered by scientists at MIT's Whitehead Institute. Just as DNA samples are used by paleo-anthropologists to study the spread of humans to different part of the world, and by evolutionary biologists to study connections among various lineages on the tree of living organisms, so too there might be ways of studying the origins of RNA, or at least the relation between RNA foldedness and biochemical function. Unlike DNA, its double-stranded cousin, RNA starts out single-stranded, but can at many places along its length double over on itself to arrive at complicated, twisted shapes.

Speaking at the APS March Meeting, Erik Schultes (MIT-Whitehead) reported on an experiment in which a particular sequence of RNA bases could, by altering one base at a time, take on rather quickly the identity of either of two very different ribozymes (RNA molecules that can catalyze reactions) with two very different functions, one for cleavage and one for ligation. Continuing to substitute different bases in a clever way, the researchers noticed that they could retain the functionality of the two RNA species (that is, the ribozymes went on performing their cleavage or ligation jobs) even though the two were getting progressively further apart in "sequence space." At the end one could look at the two contrasting ribozymes, with different function and very different sequences, and hardly suspect that they had a common origin. Schultes compared this to transforming the word cat into the word dog through a sequence of single-letter "mutations," each one of which resulted in a legitimate word: cat-cot-cog-dog (for background see Science, 21 July 2000).

At the same RNA session Ranjan Mukhopadhyay reported that he and his colleagues at NEC Laboratories in New Jersey have found that a typical RNA sequence with its 4-base chemical code folds more predictably and stably than would hypothetical RNA sequences based on a two-base or six-base "alphabet. Both 4-base and 6-base RNA proved to be more stable than 2-base RNA. Furthermore, 4-base RNA possessed more stable, foldable structures than 6-base RNA (just as it is easier to form 4-letter Scrabble words than it is to form 6-letter words).

In other theoretical work, Ralf Bundschuh of Ohio State and Terence Hwa of UC-San Diego have showed that RNA could exhibit several different "phases," just as water can exist on a pressure-versus-temperature phase diagram in the solid, gaseous, or liquid forms. In the case of RNA, Bundschuh showed mathematically, RNA could exist in a normal, glassy, molten, or denatured phase. At low temperatures, for instance, in the "glassy" phase, a given RNA sequence can get stuck in a random structure. At higher temperatures, RNA can assume a more flexible molten state, in which it is free to fold into a variety of different shapes.