Since its proposal in the 1960s, the molecular clock has become an essential tool in many areas of evolutionary biology, including systematics, molecular ecology, and conservation genetics. The molecular clock hypothesis states that DNA and protein sequences evolve at a rate that is relatively constant over time and among different organisms. A direct consequence of this constancy is that the genetic difference between any two species is proportional to the time since these species last shared a common ancestor. Therefore, if the molecular clock hypothesis holds true, this hypothesis serves as an extremely useful method for estimating evolutionary timescales. This is of particular value when studying organisms that have left few traces of their biological history in the fossil record, such as flatworms and viruses.
The Molecular Clock Is Proposed and Refined
The molecular clock hypothesis was originally proposed by researchers Emile Zuckerkandl and Linus Pauling on the basis of empirical observations, but it soon received theoretical backing when biologist Motoo Kimura developed the neutral theory of molecular evolution in 1968. Kimura suggested that a large fraction of new mutations do not have an effect on evolutionary fitness, so natural selection would neither favor nor disfavor them. Eventually, each of these neutral mutations would either spread throughout a population and become fixed in all of its members, or they would be lost entirely in a stochastic process called genetic drift. Kimura then showed that the rate at which neutral mutations become fixed in a population (known as the substitution rate) is equivalent to the rate of appearance of new mutations in each member of the population (the mutation rate). Provided that the mutation rate is consistent across species, the substitution rate would remain constant throughout the tree of life.
Subsequent research has shown that Kimura's assumption of a strict molecular clock is too simplistic, because rates of molecular evolution can vary significantly among organisms. However, there has been a general reluctance to abandon the molecular clock entirely, because it represents such a valuable tool in evolutionary studies. Instead, researchers have undertaken efforts to retain some aspects of the original clock hypothesis while "relaxing" the assumption of a strictly constant rate.
Such efforts have led to the development of so-called "relaxed" molecular clocks, which allow the molecular rate to vary among lineages, albeit in a limited manner. There are currently two major types of relaxed-clock models. The first type assumes that the rate varies over time and among organisms, but that this variation occurs around an average value. The second type allows the evolutionary rate to "evolve" over time, based on the assumption that the rate of molecular evolution is tied to other biological characteristics that also undergo evolution. For instance, there is some evidence that substitution rates are influenced by an organism's metabolic rate.
