Neutral Evolution &

Molecular Clock

Presented By Miss Aditi PatilM.Sc. Part I24/01/2009

Under the Guidance ofDr. Swati Bhavsar

Neutral Theory Of Molecular Evolution

•Motoo Kimura (1960-1970)•Does not deny natural selection•Genetic polymorphism•Neutral alleles with respect to

fitness•Random fixation of selectively

neutral mutants•Mutation and genetic drift

Relative importance of drift and selection

• Molecular

evolution

• Evolution at

phenotypic

levelFigure 1 : Balance between natural selection and random drift

Mathematical Expression Of The Neutral Theory

• If population size is N and µ is neutral mutation rate per gamete per generation at a locus.

No. of new mutations = µ X 2N

(E.g.: mutation in protein ‘x’ in experimental rat)

- given µ for the rat is 2.5 X 10 -9

- consider population size N = 50 No. of new mutations = 1.25X 10 -7

• According to drift theory,

P = 1/(2N)

where P = probability that a mutation will be fixed by drift

Thus, P for protein ‘x’ , P = 1/(2X50) = 0.01

• No. of mutations fixed per generation is,

= µ X 2N X 1/(2N) = µ

Where µ = Neutral mutation rate per gamete per generation at a locus

• No. of mutations in protein ‘x’ fixed per generation is, = 2.5 X 10 -9 X100 X 1/100 =2.5X10 -9 mutation per gamete per generation.

• Therefore, the rate of neutral evolution is theoretically constant and is equal to the rate of mutation.

Applications Of Neutral Theory

•The faster rates

•The degrees of polymorphism

•Constancy of molecular

evolution

•Zuckerkandl and Pauling (1965)

•The rate of molecular evolution

•Molecular clock

•Species divergences and constructing phylogenies

The Molecular Clock Hypothesis

Molecular Clock And Neutral Theory

•The molecular clock hypothesis

•The neutral theory prediction•Rate of evolution per

generation•Rate of mutation•Rate variation among

lineages•Constancy of the molecular

clock

Figure 2 : Proteins evolving at different rates

Causes of Rate Variation Among Lineages

• The Generation-time Effect• Nucleotide substitution rates • Substitution fixation rates• species with shorter generation

times • Higher rates of evolution• Effect of near-neutrality• offset the generation time effect

Limitations Of Molecular Clock• Changing generation times• Population size • Species-specific differences • Changes in the intensity of

natural selection

Applications Of Molecular Clock

• Molecular systematics• Correct scientific classification

of organisms• Dates of phylogenetic events• Divergence of living taxa• Formation of the phylogenetic

tree• Divergences times

References• M. Kimura, The neutral theory of molecular evolution: a

review of recent evidence, Japanese Journal of Genetics (1991), 66: 367-86.

• http://understandingevolution.com/evosite/evo101/IIIE5bNeutraltheory.shtml

• http://plato.stanford.edu/entries/evolutionary-genetics/figure2.gif

• www.pbs.org/wgbh/evolution/library/05/1/pdf/l_051_06.pdf

• http://en.wikipedia.org/wiki/Neutral_theory_of_molecular_evolution

• http://en.wikipedia.org/wiki/Molecular_clock

Thank you