Bayesian molecular clock dating of species divergences in the genomics era
The molecular clock is a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged. The biomolecular data used for such calculations are usually nucleotide sequences for DNA or amino acid sequences for proteins. The benchmarks for determining the mutation rate are often fossil or archaeological dates. The molecular clock was first tested in on the haemoglobin molecular clock dating variants of various animals, and is commonly used in molecular evolution to estimate times of speciation or radiation.
It is sometimes called a gene clock or an evolutionary clock. The genetic equidistance phenomenon was first noted in by Emanuel Margoliashwho wrote: If this is correct, the cytochrome c clcok all mammals dahing be equally different from the cytochrome c of all birds. Since fish diverges from the main stem of vertebrate evolution earlier than either birds or mammals, the cytochrome c of both mammals and birds should be equally different from the cytochrome c of fish.
Similarly, all vertebrate cytochrome c should be molecular clock dating different from the yeast clocm. Together with the work of Emile Zuckerkandl and Linus Pauling, the genetic equidistance result directly led to the formal postulation of the molecular clock hypothesis in the early s. The observation of a clock-like rate of molecular change was originally purely phenomenological. Click, the work of Motoo Kimura  developed the neutral theory of molecular evolutionwhich predicted a molecular clock.
Let there be N individuals, and to keep this calculation simple, let the individuals be haploid i. Let the rate of neutral mutations i. Rocket league matchmaking is bad most changes seen during molecular evolution are neutral, then fixations in a population will accumulate at a clock-rate that is equal to the rate of neutral mutations in an individual.
The molecular clock alone can only say that one time period is twice as long as another: For viral phylogenetics and ancient DNA studies—two areas of evolutionary biology where it is possible to sample sequences over an evolutionary timescale—the dates daing the intermediate samples can be used to more precisely calibrate the molecular clock.
However, most phylogenies require molecular clock dating the molecular clock be calibrated against independent evidence about dates, such as the fossil record. Node calibrationalso referred to as node dating, is dlock method for phylogeny dlock that is done by placing fossil constraints at nodes. A node calibration fossil is the oldest discovered representative of molecular clock dating cladewhich is used to constrain its minimum age.
Due to the fragmentary nature of the fossil record, the true most recent common ancestor of a clade will likely never be found. Determining the maximum clade age is challenging because it relies on negative evidence —the absence of older fossils in that clade. There are a number of methods for deriving molecular clock dating maximum clade clockk using birth-death models, fossil stratigraphic distribution analyses, or taphonomic controls.
There are several prior probability distributions including normallognormalexponentialgammauniformetc that can be used to molecular clock dating the probability of the true age of divergence relative to the age of the fossil  ; however, there are very few methods for estimating the shape and parameters of the probability distribution empirically. Historical methods of clock calibration could only make use of a single fossil constraint non-parametric rate smoothing while modern analyses BEAST  and r8s  allow for the use of multiple fossils to calibrate the molecular clock.
Simulation studies have shown that increasing the number of fossil constraints increases the moleculaf of divergence time estimation. Tip calibrationalso referred to as tip dating, is a method of molecular clock calibration in which fossils are treated as taxa and placed on the tips of the tree. This is achieved by gay speed dating devon a matrix that includes a molecular molecular clock dating for the extant taxa along with a morphological dataset for both the extinct and the extant taxa.
Molecular and morphological models work together simultaneously, allowing morphology to inform the placement of fossils. This method does not rely on the interpretation of negative evidence to infer maximum clade ages. In this method, the age of a fossil can inform its phylogenetic position in addition to morphology. By allowing all aspects of tree reconstruction to occur simultaneously, the risk of biased results is decreased.
One current method of molecular clock calibration is total evidence dating paired with the fossilized birth-death FBD model and a model of morphological evolution. This allows fossils to be placed on a branch above an extant organism, rather than being confined to the tips. Sometimes molecular clock dating a single divergence date can be estimated from fossils, with all other dates inferred from that.
Other sets of species have abundant fossils available, allowing the Molecular clock dating of constant divergence rates to be tested. DNA sequences clkck low levels of negative selection showed divergence rates of 0. In addition to such variation in rate with genomic position, since the early s variation among taxa has proven fertile ground for research too,  even over comparatively short periods of evolutionary time for example mockingbirds .
Tube-nosed seabirds have molecular clocks that on average run at half speed of many other birds,  possibly due to long generation times, and many turtles have a molecular clock running at one-eighth the speed it does in small mammals, or even slower. Researchers such as Francisco Ayala have more fundamentally challenged the molecular clock hypothesis. 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. These models are called relaxed molecular clocks  because they represent an intermediate position between the 'strict' molecular clock hypothesis and Joseph Felsenstein's many-rates model  and are made possible through MCMC techniques that explore a weighted range of tree topologies and simultaneously estimate parameters of the chosen substitution model.