John Maynard Smith has been described as one of the most creative biologists of the post neo-Darwinian synthesis era, with a career defined by boundless courage and curiosity ( Charlesworth 2004 Michod 2005). This is possible because functional molecules are not dispersed randomly through spaces of possible sequences, but rather, can be located in a manner analogous to the words in his example: clustered in networks, such that natural selection can serve as an effective search algorithm for locating biophysically viable protein sequences (and by extension, adaptation writ large). His main point: in order for natural selection to “locate” solutions in the vast space of possible protein sequences, incremental solution steps only need to be to other meaningful words, that is, protein forms that are functional. In this respect, functional proteins resemble four-letter words in the English language, rather than eight-letter words, for the latter form a series of small isolated islands in a sea of nonsense sequences (Maynard Smith 1970). It follows that if evolution by natural selection is to occur, functional proteins must form a continuous network which can be traversed by unit mutational steps without passing through nonfunctional intermediates. In the context of the word game, the path containing WORD, WORE, GORE, GONE, and GENE would be preferred because it contains viable, sensical English words at every step, unlike the other example four-step moves. He proposed that this could be achieved with the following four-step move: The example he used was in the transformation from “WORD” into “GENE,” using the rules from the word game. The model of protein evolution I want to discuss is best understood by analogy with a popular word game (Maynard Smith 1970). In this letter, Maynard Smith-by then a well-known theoretical biologist at the University of Sussex-compared natural selection in the context of proteins to a word game where the goal is to convert one word into another by changing one letter at a time: When effective, they capture the essence of complicated or counterintuitive ideas, can transform or reframe debates, and generate hypotheses.įebrumarked the 50th anniversary* of one of the most influential analogies ever proposed in evolutionary genetics, appearing in the 1970 letter to Nature entitled “Natural Selection and the Concept of a Protein Space,” written by Maynard Smith (1970). Metaphors and analogies have long served as central actors in scientific communication.
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