《生物系统学原理与方法》第4章Substitutionmodeles,NeutralTheoryandmolecularclock.ppt

Neutral Theory of Molecular Evolution Endorsement of the Neutral Theory Science (1969) 164: 788-798 Neutral Theory of Molecular Evolution Critiques of the Neutral Theory Neutral Theory of Molecular Evolution Inconsistencies with the neutral theory Overdispersion of the protein clock Lack of a generation time effect in protein clock Heterozygosity is much lower, and more even among species, than predicted from population size. The molecular clock The Molecular Evolutionary Clock t0 t1 As proteins (genes) diverge from a common ancestor, they accumulate changes at a constant rate Zuckerkandl & Pauling (1962, 1965) – hemoglobin Margoliash (1963) – cytochrome c Doolittle & Blomback (1964) - fibrinopeptides ? The utility of this concept lies in its application to dating diversification events e.g. Wilson & Sarich 1967 human-chimp diversification ~5my The rate at which the clock ticks fluctuates over time Time Divergence stochastic metronomic The molecular clock In order to use the molecular clock to date diversification events, you must first ensure that sequences are evolving at a relatively constant rate A B Time (mya) genetic differences the common ancestor Rate = number of genetic differences twice the divergence time of A and B Measuring Evolutionary time with a molecular clock Estimate genetic distance d = number amino acid replacements Use paleontological data to determine date of common ancestor T = time since divergence Estimate calibration rate (number of genetic changes expected per unit time) r = d / 2T Calculate time of divergence for novel sequences T_ij = d_ij / 2r The molecular clock Estimating Genetic Distance with a Substitution Model accounts for relative frequency of different types of substitutions allows variation in substitution rates between sites given learned parameter values nucleotide frequencies transition/transversion bias alpha parameter of gamma distribution can infer branch