Magazine article Natural History

An Alternative to the RNA World

Magazine article Natural History

An Alternative to the RNA World

Article excerpt

Centuries of scientific inquiry have brought us progressively closer to answering the big question: how did organisms such as ourselves come to exist? The most stunning advance so far has been the 1952 discovery of the structure of deoxyribonucleic acid, or DNA. The elegance of DNA's structure decisively solved the mystery of genetic inheritance. From opposite strands of DNA's antiparallel double helix, the nucleotide bases adenine (A) and thymine (T) always face and bind to each other, as do guanine (G) and cytosine (C). This "base pairing" explained in one stroke why the two DNA strands can be copied during cell division-a process called replication-and passed correctly from generation to generation. In doing so, it also confirmed Darwin's theory of natural selection by furnishing a solid basis for imagining how we and other living things evolved from simpler common ancestors. By connecting us in this way to our past, base pairing became essential to thinking about the origins of life.

To realize the immense power and diversity apparent in biology, however, information in the sequence of DNA bases must first be read out, and then interpreted. Analogous to transcribing drafts of a document, readout involves making a copy in a slightly different molecule called ribonucleic acid (RNA) by a process called "transcription." The RNA copy preserves the language-sequences of the A, T, C, and G bases-in which genetic information is stored, but cannot normally function without being interpreted. Interpretation uses each sequence as a blueprint for an entirely different molecule. That process, "translation," converts genetic information from one alphabet-four bases- into an unrelated one-twenty amino acids. These amino acids are strung together in various combinations to make a vast array of proteins.

Translation is not the end of the process. Once a set of amino acids has been produced, another crucial step remains before the resulting protein can function: it must fold into a unique three-dimensional configuration. Amino acids in widely separated positions along the linear protein chain form oily inclusions to avoid interacting with water. These movements eventually lead to more specific packing arrangements that, in turn, order the remaining chain. Folding organizes various amino acid groups into an active arrangement at a site in the protein.

This information flow-from DNA to RNA to protein chain to folded protein-proceeds only in one direction. Inherent redundancy of the genetic code, along with the difficulty of unfolding, copying, and reversing the translation of a folded protein, make it impossible to recover a protein's original gene sequence.

The clarity with which base-pairing solved the inheritance problem highlighted an even more challenging question. The many chemical reactions in the cell must be synchronized. Without proteins called enzymes, different reactions proceed at rates that differ by more than twenty powers of ten. Nearly all reactions in contemporary biology are therefore synchronized by enzymes that speed up the slower reactions through catalysis, so that they all have almost the same rate. Otherwise, the entire orchestra of chemical reactions would be chaotic.

An answer to this difficult question-how to satisfy the simultaneous requirement for replication and catalysis- was proposed in the mid-1960s: RNA molecules, which can carry genetic information and serve as genes, can also accelerate some chemical reactions. The hypothesis that RNA molecules might have functioned alone, as both genes and catalysts, in an early life form populated entirely by RNA, was posited independently in papers by Francis Crick and Leslie Orgel, both then at the Salk Institute, and promoted in Carl R. Woese's 1967 book, The Genetic Code: The Molecular Basis for Genetic Expression. In a 1986 paper, Nobel laureate and Harvard physicist Walter Gilbert named it "the RNA World." It was rapidly embraced by most students of the origin of life. …

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