Molecular clock

The molecular clock is a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged.

The notion of the existence of a so-called "molecular clock" was first attributed to Émile Zuckerkandl and Linus Pauling who, in 1962, noticed that the number of amino acid differences in hemoglobin between different lineages changes roughly linearly with time, as estimated from fossil evidence.

[1] They generalized this observation to assert that the rate of evolutionary change of any specified protein was approximately constant over time and over different lineages (known as the molecular clock hypothesis).

Similarly, the difference between the cytochrome c of a bacterium and yeast, wheat, moth, tuna, pigeon, and horse ranges from 64% to 69%.

Together with the work of Emile Zuckerkandl and Linus Pauling, the genetic equidistance result led directly to the formal postulation of the molecular clock hypothesis in the early 1960s.

[3] Similarly, Vincent Sarich and Allan Wilson in 1967 demonstrated that molecular differences among modern primates in albumin proteins showed that approximately constant rates of change had occurred in all the lineages they assessed.

Sarich and Wilson's paper reported, for example, that human (Homo sapiens) and chimpanzee (Pan troglodytes) albumin immunological cross-reactions suggested they were about equally different from Ceboidea (New World Monkey) species (within experimental error).

However, most phylogenies require that the molecular clock be calibrated using independent evidence about dates, such as the fossil record.

There are a number of strategies for deriving the maximum bound for the age of a clade including those based on birth-death models, fossil stratigraphic distribution analyses, or taphonomic controls.

[12] Unlike node calibration, this method reconstructs the tree topology and places the fossils simultaneously.

Expansion dating has been used to show that molecular clock rates can be inflated at short timescales[18] (< 1 MY) due to incomplete fixation of alleles, as discussed below[20][21] This approach to tip calibration goes a step further by simultaneously estimating fossil placement, topology, and the evolutionary timescale.

By allowing all aspects of tree reconstruction to occur simultaneously, the risk of biased results is decreased.

Other sets of species have abundant fossils available, allowing the hypothesis of constant divergence rates to be tested.

DNA sequences experiencing low levels of negative selection showed divergence rates of 0.7–0.8% per Myr in bacteria, mammals, invertebrates, and plants.

[25] In the same study, genomic regions experiencing very high negative or purifying selection (encoding rRNA) were considerably slower (1% per 50 Myr).

[30][31][32] According to Ayala's 1999 study, five factors combine to limit the application of molecular clock models: Molecular clock users have developed workaround solutions using a number of statistical approaches including maximum likelihood techniques and later Bayesian modeling.

In particular, models that take into account rate variation across lineages have been proposed in order to obtain better estimates of divergence times.

The inclusion of differences that have not yet become fixed leads to a potentially dramatic inflation of the apparent rate of the molecular clock at very short timescales.