• Introduction
(0) What is bioinformatics? What is computational biology? What is molecular evolution?
Two areas of study in molecular evolution: evolution of macromolecules and molecular
phylogenetics. Population genetics plus molecular biology equals molecular evolution.
Population genetics provides the theoretical foundation. Molecular biology provides the
empirical data.
• Genes, Genetic Codes, and Mutation
(1) The central dogma of molecular biology. Nucleotide sequences as strings over alphabets
with four characters. Prefixes, suffices, and substrings. Genomes and DNA replication.
Genes and gene structure. Genic and nongenic DNA. Protein-coding genes, RNAspecifying
genes, and untranscribed genes. Pseudogenes. Three domains, many kingdoms.
(2) Categorization of amino acids. Proteins as strings over an alphabet of twenty characters.
Primary, secondary, tertiary, quartenary structure. Transfer RNAs. Genetic codes
and translation. Role of the ribosome. Set theory, union, intersection. Probability, outcomes,
events. Frequency vs. axiomatic probability. Conditional probability. Random
nucleotide sequences.
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(3) Mutation. Substitution mutations, recombinations, deletions, insertions, inversions.
Transitions vs. transversions. Synonymous vs. nonsynonymous mutations. Silent mutations.
Homologous recombination. Replication slipage. Chromosomal inversions. Hot
spots of mutation.
• Dynamics of Genes in Populations
(4) Allele frequencies in haploid and diploid popluations. Hardy-Weinberg equilibrium and
relative genotype frequencies. Natural selection, fitness of genotypes, and allele frequency.
Deterministic discrete time maps, finding equilibria, classifying equilibria, and cobwebbing.
Dominant, co-dominant, and overdominant selection. Balancing or stabilizing selection vs.
directional selection.
(5) Random genetic drift. Gamete sampling in a diploid population. Binomial probability
distribution. Stochastic model of allele frequencies with no selection. Cumulative behavior,
fixation, and loss. Example Matlab scripts. Expectation and variance of a random variable.
Effective population size. Dynamics of gene substitution. Fixation probability and fixation
time for a new allele. Conditional fixation time. Rate of gene substitution for neutral
mutants vs. advantageous mutants. More Matlab examples.
• Evolutionary Change in Nucleotide Sequences
(6) Mathematical modeling of nucleotide substitution in a DNA sequence. Derivation of
the Jukes-Cantor model. Matrix-vector notation for continous-time Markov chains.
(7) Kimura’s two-parameter model. Number of nucleotide substitutions between two DNA
sequences that share a common origin is greater than the Hamming distance. Modeling
nucleotide divergence between two sequences that share a common origin using Jukes-
Cantor and/or Kimura’s two-parameter model.
(8) Edit distance between two sequences. Similarity scores and distance between two sequences.
Are methods of scoring alignments arbitrary? Alignment of nucleotide and amino
acid sequences. A dynamic programming algorithm for longest common subsequence problem.
(9) A dynamic programming algorithms for global, semi-global, and local sequence alignments.
(10) Multiple alignments. Sum-of-pairs scoring. Induced pair-wise alignments. Star alignments.
(11) Scoring schemes used when comparing amino acid sequences. Point accepted mutation
(PAM) matrices. Constructing a 1-PAM matrix from list of accepted mutations and
probability of occurrence of each amino acid. PAM matrices define discrete-time Markov
chains and evolutionary models. PAM matrices can be used to construct scoring matrices
that reflect important chemical and physical properties of amino acids.
• Rates and Patterns of Nucleotide Substitution
(12) The driving forces in evolution. Mutationism, neutralism, and selectionism. The
synthetic theory of evolution (selectionism). Adaptation. The Panglossian paradigm. The
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neutral theory of molecular evolution (neutralism). Neutrality tests. The distribution of
fitness values of mutant alleles.
(13) Pattern vs. rate of substitution. Causes of variation in substitution rates. Case study
of lysozyme and forgut fermenters. Patterns of substitution in pseudogenes. Methylation,
deamination, and loss of CG in pseudogenes. Detection of stand inequalities in mutation
rates. Patters of amino acid replacement. Conservative vs. radical replacements. Degree of
conservation of bulkiness, hydrophobicity, polarity, optical rotation, and charge. Stability
index for amino acids. Amino acid frequency is determined by nucleotide composition and
the number of codons for the amino acid! Codon-usage bias.
(14) The molecular clock hypothesis. Relative-rate tests. Causes of variation in substitution
rates among evolutionary lineages (generation times, metabolic rate). Local clocks.
Rates of substitution in organelle DNA RNA viruses. The tempo of evolution (phyletic
gradualism vs. punctuated equilibrium). No clear relationship between rates of molecular
and morphological evolution!
• Molecular Phylogenetics
(15) Objectives of phylogenetics. Species concepts (intuitive, morphological, phenetic, biological,
evolutionary/phylogenetic). The Linnaean-Simpsonian hierarchy. Reproductive
barriers and species creation. The impact and advantages of molecular data on phylogenetic
studies.
(16) Terminology of phylogenetic trees (root, internal nodes, internal branches, external
branches, terminal notes). Bifurcation vs. multifurcation. Rooted and unrooted trees.
Cladograms vs. phylograms. Newick format. Cladogenesis vs. anagenesis. True and
inferrred trees. Monophyletic groups and natural clades. Sister taxa. Paraphyletic taxa.
Convenience taxa (e.g., reptiles).
(17) Data types and phylogenetic trees. Characters vs. distances. Unordered, ordered,
and polar characters. Symplesiomorphy, synapomorphy, autapomorphy, and homoplasy.
Methods of tree reconstruction. Distance matrix methods (UPGMA, neighbor-relations,
neighbor joining). Maximum parsimony methods. Variant, invariant, informative, uniformative
traits. Maximum likelihood methods.
(18) Bayesian inference of character evolution.
Reference