1. Review of the central dogma

1. Human genome consist of
2. Replication
3. Coding sequence

                                                            i.     Gene

                                                           ii.     Protein

                                                          iii.     Genome

3. Genetic code
2. Genetic Variations
• Peppered moth evolution
• gnomad browser (genomic data aggregated by Broad Institute)
• History of mathematical models developed in the 1930s by Fisher, Wright, Haldane, Kimura ...
3. Mutations, DNA variation
1. Human (diploid) genome consist of two copies of DNA [each 3x10^9 base pairs longs] inherited from father and mother
   • Typical variations is around 3x10^6 Single Neucleoide Polymorphisms
     • SNPs, obtained by genotyping: A list of SNPs with two letters for two nucleotides, for comparison with population frequency, X, of alleles
     • Current understanding limited to x>10^{-5}
     • alleles are possible states of a locas, mostly two-allele SNPs, with rare three allele cases
   • Mutation rate in humans is roughly 2x10^{-8} per bp, per generation (in germ line) -> few hundred new mutations per child
2. Coding regions (genes, exons) constitute roughly 1 to 2% of the entire genome [roughly 6 new mutations per child]
3. Synonymous mutations result in the same amino-acid 
4. Non-synonymous  [roughly 4 new mutations lead to new amino-acids in the exome]
4. Foundations of genetics
1. One locus

                                                         i.     Genotype

                                                         ii.     Haploids vs diploids

                                                        iii.     Homo/heterozygosis, allele frequency

                                                         iv.     Dominant vs recessive: blood types

2. Random mating: Hardy-Weinberg equilibrium
3. Genetic Drift
1. Forces of Evolution
   • Mutations, recombination
   • Selection
   • Reproduction
   • Migration
2. Dynamics in population of constants size
3. Reduction of heterozygosity
4. N>>1, Binomial sampling
5. Probability of fixation
6. Time to fixation
4. Mutations
1. Random allele model
2. Steady state
5. Varying population size

(Mirny 2009 lecture notes)

(Kardar lecture notes)

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8.592  lec2-- last update    9/5/24     by M. Kardar