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Molecular Clock

Zuckerkandl and Pauling (1965) were the first to propose that various proteins and DNA sequences might evolve at constant rates over time, and thereby provide internal biological timepieces for dating past evolutionary events. The concept of a molecular clock fits well with neutrality theory because the rate of neutral evolution in genetic sequences is equal simply to the mutation rate to neutral alleles. However, clock concepts are not necessarily incompatible with selectionist scenarios. If a large number of assayed genes was acted on by multivarious selection processes over long periods of time, short-term fluctuations in selection intensities might tend to average out and the magnitudes of overall genetic distance between isolated taxa could well be correlated strongly with the time elapsed since common ancestry.

Few concepts in molecular evolution have been more debated (or abused) than those concerning molecular clocks. At the outset, three general points must be understood. First, the debate is not whether molecular clocks behave metronomically, like a working timepiece—they do not. If molecular clocks exist, both neutralists and selectionists predict at best a "stochastically constant" behavior, like radioactive decay (Ayala, 1982c; Fitch, 1976). Second, not all molecular phylogenetic applications hinge critically on the reliability of molecular clocks. For example, genetic characters likely to be of monophyletic origin (such as gene duplications or differences in gene arrangement) remain powerful as phylogenetic markers, regardless of the rate of evolution at the level of DNA sequence; and, appraisals of genetic identity and parentage (e.g., DNA fingerprinting) hardly depend on a steady pace for DNA sequence evolution. Many tree-building algorithms based on genetic distance matrices relax assumptions of rate homo­geneity among lineages , and indeed branching orders, in principle, can be inferred directly from distributions of qualitative character states using techniques such as cladistic or parsimony analyses that remain valid irrespective of whether molecules evolve in strictly time-dependent fashion. Nevertheless, data and concepts pertaining to molecular clocks are of funda­mental importance in many phylogenetic contexts.

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