Origin of genetic variation – Chapter 8
DNA makes up an organism’s genome
• Nucleotide base pairs
– Purine
• Adenine (A)
• Guanine (G)
– Pyrimidine
• Thymine (T)
• Cytosine (c)
Chromosome
• Each contains a single long DNA molecule
• A gene is a sequence of DNA that is transcribed into RNA plus its transcription
regulators
• A locus is the chromosome site occupied by a particular gene
– Sometimes refers to gene itself
Transcription
• Transcription regulated by untranscribed control regions – enhancers and
repressors
• Transcribed region consists of coding regions (exons) and non-coding regions
(introns)
• Introns are removed by splicing
• Alternative splicing can result in several proteins being encoded by a single
gene
– 35% of human genes are subject to alternative splicing
Every three nucleotides codes for an amino acid or stop sequence
Repeat sequences
• 45% of human genome is repeat sequences
– Microsatellites
– Tandem repeats
– SINEs
– LINEs
• Last three types were formed by or are capable of transposition
– Transposable elements
Gene families
• 40% of human genome are members of gene families
– Groups of genes that are similar in sequence and often function
– Some are psuedogenes
• Sequences that resemble functional genes but have internal stop codons
Hemoglobin gene family
Mutation
• What is it?
• What causes it?
• How fast does it occur?
• What are its effects?
What is mutation?
• The ultimate source of genetic variation
• Any change in the nucleotide sequence of DNA
– The word mutation can refer to both the process of alteration of a gene or
chromosome and to is product, the altered state of a gene or chromosome
• For historical reasons, mutations are sometimes referred to in terms of
phenotypic effects
– Changes in alleles rather than DNA sequences
What is mutation?
• Base substitutions
– Synonymous
– Non-synonymous
• Insertions and deletions
• Duplications
• Inversions, translocations, polyploidy
Point mutations
• Alteration of a single point in the base sequence of a gene
• Sickle cell anemia is caused by a single amino acid change at position number
6 in the protein chain, which is 146 amino acids long
– Caused by an adenine instead of a thymine at nucleotide 2 in the codon for
amino acid 6
Point mutations
• Cause by random errors in DNA synthesis or random errors in the repair of
sites damaged by chemical mutagens or high-energy radiation
• Result from reactions catalyzed by DNA polymerase
Point mutations
• Transition: Substitution of a purine for a purine
• Transversion: Substitution of a pyrimidine for a purine or vice versa
• Transitions outnumber transversions by 2:1
• Frameshift mutations caused when a single base pair becomes inserted or
deleted from a DNA sequence
Point mutations
• Nonsynonomous or replacement substitutions result in an amino acid change
• Synonomous or silent site mutations result in no change in amino acid
Recombination
• Relies on precise alignment of DNA sequences in meiosis
• Intragenic recombination occurs when homlogous DNA sequences differ
• Unequal crossing over causes duplication on one chromatid and deletion on
another
Recombination
• Generates a great deal of variation within populations
• Recombination can both retard adaptation by breaking down favorable gene
combinations and can enhance adaptation by having many combinations of
alleles that have arisen by mutation
Transposable elements
Effects of TEs
• Destroy function when inserted in coding region
• Alter gene expression when inserted in control region
• Increase mutation rate of host genes
• Insert DNA copies and RNA transcripts of other genes – retrosequences
– Most retrosequences are psuedogenes
• Can increase in number by transposition and unequal crossing over
• Rearrangements in host genome during recombination (deletion or inversion)
Transposable elements
Examples of mutations: FOXP2 gene
Mutations of the karyotype
• Polyploidy
– Increase chromosome number by union of unreduced gametes of same
species (autopolyploidy) or by hybridization by closely related species
(allopolyploidy)
– Important in speciation
Alterations of the karyotype
• Chromosome rearrangements
– Inversions
• Rearranged gene order due to chromosome looping and breakage
– Translocations
• Exchange of segments between two nonhomologous chromosomes
– Fissions and fusions
How do we measure mutation rate?
• Most data on mutation rates comes from analyses of loss-of-function
mutations and phenotypic effects
• VERY small, 10-4 to 10-8 per generation
• Varies with generation time of organism
– Mutation rate per cell division is similar among taxa
– Rate is 10-6 to 10-5 per gamete per generation
How do we measure mutation rate?
• Example: Achondroplastic dwarfism
– Autosomal dominant
– 1/10,000 births from normal parents
– This is 1/20,000 gametes
– Rate is .00005
mutations/gamete/generation
How do we measure mutation rate?
• Bacterial chemostats (LARGE populations)
Rate of mutation
• Molecular methods used to express mutation rates per base pair
– About 10-9 per base pair per generation
– Mutation rates vary among genes and chromosome regions and with
environmental factors
Mutation rates
• Mutation rates summed over the entire genome can be significant
– Genome of humans has 3,200,000,000 base pairs
– For example, in a population of 500,000 humans, at least 800,000 new
mutations arise every generation
Polygenic characters
• Variation in a typical phenotypic character is based on several to many
different genetic loci
• Difficult to determine mutation rate per locus
– Estimate mutational variance – increased variation caused by new
mutations in each generation
Mutation rate
• Mutation rate alone does not cause a character to evolve from one state to
another
– 70,000 generations for a mutation with a rate of 10-5 per gene per
generation to reach a frequency of 75% in the population
What are its effects?
• Random with respect to adaptive significance
• Mutations may have phenotypic effects, which may affect survival or
reproduction
• Most mutations are neutral or negative in effect
Alterations of the karyotype
• Many organisms that are aneuploid fail to develop properly
Homeotic mutations
Dominance
• Describes the effect of an allele on a phenotypic character when it is paired
with another allele
• Complete dominance
– Recessive
• Incomplete dominance
– Additive inheritance
Effects of mutations on fitness
• Some mutations are neutral
• Average effect of mutations is deleterious
• Fitness consequences of mutations depends on environment
• Most mutations are pleiotropic – affect more than one character
Higher the selection coefficient, the more the mutation reduces fitness
Advantageous mutations
• If there were no advantageous mutations, evolution would not occur