8.592J - HST.452J (Fall 2026)

Statistical Physics in Biology

Lecture 1

Outline

A random walk in biological physics, motivated by statistical physics, and organized according to:

I.   Sequence nucleic acids in DNA/RNA; amino-acids in proteins, shaped by mutations and fixation  [population genetics]
information
II.  Structure DNA double helix; RNA secondary form; protein folding  [Polymer physics]
interaction
III. Function building blocks of force and motion: membranes, tubules, motors, ... [non-equilibrium methods]
cooperation
IV. Emergence networks: modules, patterns, collective dynamics, ... [emergent phenomena]
complexity

Preliminary schedule of activities

Foundations of molecular evolution and population genetics

  1. Review of the central dogma
    1. Human genome consist of
    2. Replication
    3. Coding sequence

                                                            i.     Gene

                                                           ii.     Protein

                                                          iii.     Genome

    1. Genetic code
  1. Genetic Variations
  2. 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]
  3. Foundations of genetics
    1. One locus

                                                         i.     Genotype

                                                         ii.     Haploids vs diploids

                                                        iii.     Homo/heterozygosis, allele frequency

                                                         iv.     Dominant vs recessive: blood types

    1. Random mating: Hardy-Weinberg equilibrium
  1. 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
  2. Mutations
    1. Random allele model
    2. Steady state
  3. Varying population size

(Mirny 2009 lecture notes)

(Kardar lecture notes)

8.592  lec1- last update  9/2/2026   by M. Kardar