Inferred prediction, probability theory

With tree analysis it is possible to infer sequences of ancestral proteins and probable evolutionary pathways to their modern descendants.1 The advent of site-directed mutagenesis makes possible the recreation of evolutionary intermediates based on these predictions. One may then compare the properties of reconstructed intermediates with one another and with proteins from contemporary creatures. These comparisons provide a way of testing theories about the mechanism of molecular evolution. For example, this approach has provided a new criterion for distinguishing between neutral and nonneutral events.2 This chapter describes the use of site-directed mutagenesis to recreate ancestral lysozymes and presents methods of evaluating their properties. 

Nearly every inference we make with respect to any future event is more or less doubtful. If the circumstances are favourable, a forecast may be made with a greater degree of confidence than if the conditions are not so disposed. A prediction made in ignorance of the determining conditions is obviously less trustworthy than one based upon a more extensive knowledge. If a sportsman missed his bird more frequently than he hit, we could safely infer that in any future shot he would be more likely to miss than to hit. In the absence of any conventional standard of comparison, we could convey no idea of the degree of the correctness of our judgment. The theory of probability seeks to determine the amount of reason which we may have to expect any event when we have not sufficient data to determine with certainty whether it will occur or not and when the data will admit of the application of mathematical methods. 

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