Basic Graduate Evolution

Table of Contents


Review genetic basics 2013-01-15 Tue


nucleotide ≅ base


  • purines (A T), 3 H bonds, less stable (fewer bonds)
  • pyrimidine (GC), 3 H bonds
RNAnormally single stranded
DNAdouble stranded

Each strand has a 5' end and a 3' end. The convention is to write from the 5' and to the 3' end when transcribing DNA. The strands are anti-parallel.

RNA (as compared to DNA)

  • single stranded
  • much shorter (often 20-24 nucleotides long)
  • Bases: (A C G U)


  • traditionally, something that codes for a protein, i.e., gene → messenger-RNA → protein (this was previously the only functionality known for DNA segments)
  • now, genes also include sequences which do other things, e.g., transcribe RNA, some RNA sequences are functional as themselves

Types of Genes

  • protein coding
  • RNA
  • regularity

Eukaryotic protein coding genes comprise both transcribed () and non-transcribed () parts.

Gene's are transcribed by polymerase, which first anchors to a "promoter region" which flanks the gene, and then travels the gene transcribing its contents.

A "codon" is 3 nucleatides which are transcribed into 1 amino-acid.

Gene Structure (we're talking about protein coding gene)

TATA box
in the promoter region -19 from the gene start, in a GC-rich region of the DNA. Not required, but prevalent

A Gene with the promoter region.

    promoter region       Gene->
  ---->  --  <---  --     ----------   --------   ---------
  GC    CAAT   GC  TATA    
  box    box  box  box   

RNA polymerase

IIprotein coding
IIIsmall RNA
  • Genes specifying proteins

    Transcription and Translation process

    1. DNA -> pre-RNA (which does include non-coding introns)
    2. pre-RNA -> mature mRNA, this is done by the spicing machinery (these arose early in evolution and are very intricate machines). Genes are spliced using the "GT-AT rule" (introns often start with GT and end with AG)
    3. Mature mRNA -> the remainder of the gene is split up into codons and transcribed, it must start with one of three start codons (UGA UAA UAG). The start code does not code for an amino acid. This is still capped by small untranslated sections on either side.
    4. Protein -> only the translated regions converted to amino acids

    There are many other regulatory sequences in introns or between genes which do things like increase or decrease the speed of translation.

  • RNA-specifying genes (transcribed to RNA, not translated to protein)
    • transfer RNA
    • ribosomal RNA
    • similar sequences between (eukaryotes and prokaryotes) which means they arose early and are important

    Degenerate genetic code

    • 20 Amino Acids
    • 64 codons (4 × 4 × 4)
  • Regulatory Genes
    • regulate the expression of another gene
    • not transcribed or translated

    enhancers or repressors (change tempo of translation)

    notable examples

    replicator genes
    initialize and terminate replication
    "cap" at the end of a chromosomes, these erode with age, these don't erode as quickly in sea turtles
    segregator genes
    help split the DNA pair (sisters) for translation, this is where the zippers attach to unzip
    recombination genes
    sites for recombination during meiosis (crossover more likely to happen here)

Amino Acids

Composed of

  • a central carbon
  • an amino end
  • a carboxyl end
  • a hydrogen
  • a side chain – this is the most variable and the most important

Simplest is glycine

  • single H side chain
  • fits in nooks and crannies of proteins

Five classes

  • positively charged
  • negatively charged
  • hydrophobic
  • neutral
  • special


string of amino acid

  • secondary structure – two most common 2-D structures for folded proteins
    • α helix
    • β pleated sheet
  • tertiary structure – these combine into 3-D structures of the protein
  • quartinary structure – two tertiary molecules

More genetic basics 2013-01-17 Thu


Losing the phase (correct codon alignment) can be caused by mutations and garbles the translation resulting in a garbled protein. The phase is determined by the start or initiation codon, and is called the "reading frame" or "open reading frame" (ORF).


Genetic code is degenerate but not ambiguous.


Multiple codons coding for an amino acid will often differ in the third position.


fourfold-degenerate site
any nucleotide in this position will specify the same amino acid.
twofold-degenerate site
two of the four nucleotides at this position will specify the same amino acid.
non-degenerate site
every nucleotide here results in a different amino acid, called an "amino-acid substitution".
synonymous codons
different codons which code for the same amino acid.

In most codons the first two positions are non-degenerate sites.

numbers of codons

  • 61 sense codons (remaining 3 are STOP codons)
  • 549 possible codon nucleotide substitutions
    • 61 codons × 3 positions × (4-1) alternatives for each position
  • assuming equally probable mutations (not true), then 70% of all 3^{rd} position changes are synonymous
  • 2^{nd} site is the most sensitive to substitution, 0% of changes are synonymous
  • in the 1^{st} site only 4% of changes are synonymous

Main evolutionary forces (on populations)

  • mutation
  • selection
  • migration (new alleles from outside)
  • drift


Mutations are hereditary changes in the genetic material due to errors in DNA replication or DNA repair.

Types of mutations

  • substitutions
  • recombination (crossing-over and gene conversion)
  • deletions/insertions ("indels")
  • duplication
  • inversions

Evolutionarily mutations that occur in germ cells are the only hereditary ones.

  • classes of mutations
    • substitutions
      also called "point mutations"


      1. transitions (purine to purine, pyrimidine to pyrimidine), there are four possibilities for this
        • a ↔ g
        • t ↔ c
      2. transversions change the type, there are eight possibilities for this

      If these were equally likely you would expect twice as many transversions as compared to transitions.

      You actually see many more transitions than translations.

      Also classified by effect (only applies to protein coding genes)

      1. silent or synonymous (no amino acid change)
      2. replacement or non-synonymous (cause aa change)
        • missense (now codes a new aa)
        • nonsense (changes to a termination codon, will prematurely terminate translation)
    • crossing-over and gene conversion
      homologous recombination
      occurs between strands which are similar through a shared common ancestry

      This happens most often during repair. Say a chromosome breaks (very common) there is a machine which comes along and repairs the broken chromosome (sometimes this causes a change).

      This also happens during meiosis.

      Two types of homologous recombination

      1. crossing over (reciprocal recombination), two chromosomes pair up and each gets a bit of the other
      2. gene-conversion (nonreciprocal recombination), a bit of one goes to another, but one remains unchanged
    • insertions and deletions
      unequal crossing over
      May be caused by unequal crossing over, this is often caused by similar sub-sequences, this could cause an insertion and a deletion. Generally 10-13 nucleotides long.
       -----=====-----                -------------
         ---------======-----     -----====---====------
      replication slippage
      (look up in a text book), when a repeating pattern is offset. These can be thousands of base pairs long
      Selfish elements which are prone to copy themselves anywhere throughout the genome (discovered by Barbara McKlintoc in corn). Sometimes these elements will grab a nearby section of the sequence and bring them along.
    • inversion
      A rotation of a double-stranded segment by 180.
       |     |
      a b c d e f g h
      a d c b e f g h

      These often occur between genes where they don't have much effect.

  • spatial distribution of mutation
    Often 100-fold differences in mutation rates between elements of the sequence. These are often very repetitive sequences of the genome.

    Some groups of nucleotides are prone to change. E.g., CG is easily methelated causing the C to become a T. TT is also a hot spot.


    epigenetics (non-genetic), e.g., chemical elements changing genetic interpretations.

    • chemicals inhibiting expression
    • proteins binding up DNA into little balls, by histomes, this inhibits transcription
  • substitution in non-coding sequences and pseudo-genes
    important to determine the pattern of spontaneous mutation

    no selective pressure

    mutation accumulation experiments, you maintain the lowest possible population size

    you could bottleneck a population, no selection, only genetic drift

    Pseudo-genes are dead (premature STOP or something), these can also indicate baseline rates.

    • can compare to an active duplicate
    • can compare to a homolog (inactive in people, compared to active in chimps)

    Trend from GC to AT, so non-coding regions become AT-rich.

Dynamics of Genes in Populations 2013-01-22 Tue

Why does population size matter?
Selection does not work in small populations.

Evolution as a population-level process

Big "macro-level" changes (e.g., between species) are results of the same small "micro-level" changes between individuals.

Four major evolutionary forces

  • mutation
  • random genetic drift – ∃! animal, the Atlantic eel, which has an effectively infinite population size, because they all come together to one place annually to mate.
  • natural selection
  • gene flow

The study of gene changes in populations is population genetics.

  • what influences mutant allele over time
  • how is genetic variability maintained
  • probability of going to fixation
  • how fast will replacement take place
  • influence of chance effects on molecular genetic change


chomosomal location of a gene (often a synonym for gene)
alternate forms of a gene
allele frequencies
relative proportions of alleles in a population
genetic constitution of an individual
observable characteristic or trait of an organism
discrete trait
finite number of phenotypes in discrete classes, often controlled by one or a few genes
continuous or quantitative trait
what is sounds like, controlled by at least 100 genes, most traits fall into these categories
homozygous vs. heterozygous
whether alleles are of the same type or different
genotypic vs. phenotypic ratios
dominant vs. recessive allele
change in allele frequency
natural selection
differential reproduction of genetically distinct individuals or genotypes within a population
fitness (w)
measure of an individuals ability to reproduce
  • absolute fitness – total progeny (might only count progeny which make it to reproductive age)
  • relative fitness – progeny relative to rest of the population, the most fit genotype is assigned a fitness of 1

Punnett Square

  • BB is homozygous
  • Bb is heterozygous

Mendel bred purple × purple plants and got both purple and white plants. Specifically 705 purple and 224 white.

Diploid parent will produce single-ploid gametes (else there would be a combinatorial explosion in the ploidy of the offspring).

A Punnett Square

pistilBBB (purple)Bb (purple)
bBb (purple)bb (purple)
  • phenotypic ratio of above is
    • 3 purple
    • 1 white
  • genotypic ratio of above is
    • 1 BB
    • 2 Bb
    • 1 bb

Changes in allele frequencies


  • 1000 peppered moths in Manchester
  • dark melanic form of allele is dominant (M)
  • ancestral is recessive (m)
  • 825 melanic
  • 175 peppered
  • 512 of melanic are heterozygous

Some calculations

  • Phenotypic ratio is 875/175 or 4.7 melanic to peppered
  • Genotypic ratio is 313 MM, 512 Mm, 175 mm or 1.78 : 2.93 : 1
  • Allele frequencies of M and m 616 + 512 / 2000 = 0.569 (2 * 175) + 512 / 2000 = 0.431

Allele frequencies are changed by

  • selection
  • drift
  • migration

2 Mathematical approaches

(analytic) can predict changes unambiguously. The first of these was "Harvey Weinberg".
probabilistic, associates probability distributions with environmental conditions

Deterministic assumptions

  • infinite population size
  • constant environment

Needed for Darwinian selection (influenced by Menthusian principles)

  • variation
  • environmental limit to population size (carry capacity)
  • differential reproduction (because of the above)

Types of mutation

                +------------ mutation ------------------+
                |                  |                     |
                |                  |                     |
                |                  |                     |
           deleterious          neutral            advantageous
                |                  |                     |
                |                  |                     |
                |                  |                     |
                |                  |                     |
           purifying            chance             positive selection
           selection            events                   or

Normally selection reduces genetic variation, however "overdominant" selection can increase genetic variation. This is when the heterozygote has the highest fitness.

Hardy-Weinberg principle

1 locus, 2 alleles (A_{1} A_{2})

  • 3 possibly diploid genotypes
  • allelic frequencies are
    • f(A_{1}) = p
    • f(A_{2}) = q
    • p + q = 1

genotypic frequencies

  • f(A_{1}) = p^{2}
  • f(A_{2}) = 2pq
  • p + q = q^{2}

This is the null model.

Back to our problem.

  • melanic is dominant and is 87% (could be heterozygotes)
  • → 13% is non-melanic
  • → q = 0.13
  • → q = \sqrt{0.13} = 0.36
  • → p = 1 - q = 0.64
  • → f(Mm) = 2pq = 2 × 0.36 × 0.64

Graph (frequency of a, by frequency of genotype in population)

set xrange [0:1]
set xlabel 'frequency of A'
plot x * x title 'AA', (1-x) * (1-x) title 'aa', 2 * x * (1-x) title 'Aa'


Natural Selection changes allelic frequencies

genotypeA1 A1A1 A2A2 A2
afterp * p w112pqw12q * q * w22
\begin{equation*} q' = \frac{pqw_{12} + q^{2}w_{22}}{p^{2}w_{11} + 2pqw_{12} + q^{2}w_{22}} \end{equation*}

change in frequency \begin{equation*} \delta q = q' - q \end{equation*} \begin{equation*} \delta q = \frac{pq(p(w_{12} - w_{11}) + q(w_{22} - w_{12}))}{p^{2}w_{11} + 2pqw_{12} + q^{2}w_{22}} \end{equation*} Example

  • heterozygous individuals have lighter eye spots (increased predation)
  • relative fitness of genotypes
  • p(S) = 0.7

p = 0.7 q = 0.3

Frequencies in the original


Relative fitness


Next generation frequencies

  • f(SS)' = p^{2}w_{11} = 0.49 × 1
  • f(Ss)' = 2pqw_{12} = 0.42 × 0.9
  • f(ss)' = q^{2}w_{22} = 0.09 × 0.6

Next generation's allelic frequencies

  • f(SS) × 2 + f(Ss)
  • f(ss) × 2 + f(Ss)


Heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.