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just a matter of time before we collect them all), computer searches will turn up only weak similarities. Before attempting to read biological significance into such weak similarities, one must evaluate their statistical significance. Not surprisingly, this is an area in which mathematics has much to offer molecular biology. To motivate the study of the statistical significance of sequence similarities, we consider a single data set that provoked a great deal of excitement a few years ago when a team of researchers thought that they saw extraordinary clues about early evolution in the sequences of genes encoding certain ribonucleic acid (RNA) molecules.

The origin of the universe and the origin of life are topics of wide interest to both biologists and nonbiologists. One approach to studying the origin of the universe is to listen to faint echoes from the Big Bang. Similar approaches are used in studying the origin of life. Are there any molecular echoes remaining from the origin of life? Each of the three key molecules in molecular biology—DNA, RNA, and protein—has been championed by some theorists as the earliest self-replicating molecule. Proteins have seemed attractive to some because of their ability to catalyze chemical reactions. DNA has seemed attractive to others because it is a stable store of information. Lately, however, RNA has taken the lead based on the well-known ability of RNA to encode information in the same manner as DNA and the recently discovered ability of RNA to act as nonprotein enzymes that are able to catalyze some chemical reactions. These properties suggest that some RNA sequence might have been able to achieve the key feat of self-replication—serving as both self-template and replication enzyme. Thus, life may have started out as an RNA world.

As indicated in Chapter 1, modern RNAs come in three varieties: messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). mRNAs are the messages copied from genes. rRNAs are components of the macromolecular structure, called the ribosome, used for translating RNA sequences into protein sequences. tRNAs are the ''adapter molecules" that read the genetic code, with an anticodon loop recognizing a particular codon at one end and an attachment site for the amino acid corresponding to this codon at the other. rRNAs and tRNAs are clearly ancient inventions, necessary for the progression from life based only on RNA to organisms employing proteins for efficient catalysis of biochemical reactions.

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