Bio120 Lec 4: Genetic Variation II: Models and Measurement

Fisher, Haldane and Wright

• Mathematical evolutionary theory for population genetic change

• uses statistical and probabilistic models to track how allele and genotype frequencies change over time

• Provided the foundations for “Neo-Darwinism” and the

  “New Synthesis” (combination of darwin and Mendels concepts)

• Continuous variation and Darwinian natural selection are

  entirely consistent with Mendel’s Laws

• Demonstrated the evolutionary significance of genetic

  variation

Metrics of genetic variation

• Hetrerozygosity

• Polymorphism

Heterozygosity

the fraction of an individual in a population that carries 2 alleles

Polymorphism

• Proportion of gene loci that have 2 or more alleles in the population

• A locus can be polymorphic without being heterozygous

  • ex. different homozygous traits on the same locus of different genes

• monomorphism is every locus having the same gene

Forces that influence patterns of genetic diversity and evolution

• mutation

• genetic drift

• gene flow (migration)

• natural selection

• recombination

Mutation

• Ultimate source of genetic variation

• mutations are rare

• Caused by errors during replication (not directed)

• Increases genetic variation in populations

• mutations mostly decrease the fitness of an organism

Recombination

• crossing of chromosomes

• generates halotype diversity (i.e., new haplotypes)

  • Halotypes: a set of alleles on a single chromosome inherited from one parent

• Increases genetic variation in populations (increased haplotype diversity)

Genetic drift

• Change in the frequency of an existing gene variant (allele) due to random chance.

• random sampling affects every generation

• more important in small population

• decreased genetic variation in populations

  • remove gene versions (alleles) from a population over time

Natural Selection

• negative (purifying selection)

  • Mutations that reduce fitness are removed by natural selection

  • Decreases genetic variation in populations

• Positive (directional selection)

  • Mutations increase fitness and eventually become fixed in a population (fixation: he process by which a specific allele (gene variant) reaches a frequency of 100% in a population's gene pool, permanently eliminating all alternative variants at that specific genetic locus)

  • Decreases genetic variation

• Selection favouring maintenance of multiple alleles (balancing selection)

  • Maintain diversity over the long term

  • increases polymorphism

  • increase in heterozygostity

  • increases or keeps genetic variation

Gene flow (Migration)

• movement of genetic material from one population to another

• introduces alleles from population 1 to population 2

• movement directly shapes how biological, genetic, or cultural traits are organized and distributed across vast geographic areas

• decreases difference/ variability between population

• increases genetic diversity within the population

What influences patterns of genetic diversity and evolution?

mutation: increase diversity

recombination: increases diversity

Genetic drift: decreases diversity

Natural selection: increases or decreases diversity

Migration: increases diversity

Models of population genetic variation

• mutation-selection balance

• selection maintaining varaiation

Mutation-selection balance

• Mutation and purifying selection dominate evolution

• Less fit types (re)introduced by mutation

• Followed by selection acting to remove them

• Most genetic variation in populations is deleterious & transient

• Called the “classical school”

Selection maintaining variation

• Balancing selection dominates evolution

  • Heterozygote advantage

  • Frequency-dependent selection

• Fitness varies across space and time

• Called the “balance school”

Classical school vs Balance school

represent two famous historical, contrasting views in evolutionary genetics regarding how much genetic variation exists within natural populations and how natural selection acts on that variation

Classical school

• Morgan and Muller

• not much genetic diversity within a population

• low heterozygosity

• low polymorphism

• wild type is normal genotype/ ideal genotype which is homozygous

• Negative selection: selection typically negative: removes deleterious alleles

Balance school

• Ford and Dobansky

• there is variation within a population

• high heterozygosity

• high polymorphism

• heterozygote advantage

• balance selection: selection favours/ maintains diversity

Genetic “Markers”

a specific DNA sequence with a known physical location on a chromosome that scientists use to track inheritance or identify individuals and species

• morphological

• cytological

Morphological marker

observable physical or structural traits—such as size, shape, color, and cellular architecture

Cytological marker

a distinctive structural feature on a chromosome - such as a specific banding pattern, size, shape, or translocation—that can be identified under a microscope

Genetic Evidence for the Existence of Genetic Variation

• continuous polygenetic traits

  • conduct artificial selection experiments on different groups of organisms

  • Involves controlled breeding of individuals with particular traits for many generations

  • selection response in corn:

Evolutionary Responses of Continuous Traits

• Demonstrate existence of ample heritable variation in fitness-related

phenotypes

• Are due to many underlying genes (see the continuous response to

selection)

Richard Lewontin

• realized that protein provides information on allelic genetic variation that you cant see

• ectrophoresis revolution Allozyme* gel electrophoresis provided a way to ask:

  • “What proportion of genes or individuals show genetic variation (P & H)?”

  • Answering it addresses a fundamental dispute between classical and balance schools

• Initiated large scale surveys of electrophoretic variation in enzymes & proteins in diverse organisms

• found that individuals have 2 bands of protein meaning it contains both alleles that influence proteins

First Allozyme Studies: Genetic Variation is very high

1. Mutation-selection balance (classical school)

• harmful or less fit genetic variant persists in a population not because natural selection favors it, but because new mutations keep recreating it at the exact same rate natural selection eliminates it.

2. Selection maintaining variation (balance school)

• Heterozygote advantage

• Frequency-dependent selection

• Fitness varies across space and time

3. Selectively neutral variation

• Different types do not differ in their fitness relative to one another

• New mutations neither eliminated nor retained by selection

Advantages of Studies of Enzyme Polymorphism

• Many loci can be examined

• Can be used in nearly any organism

• Loci co-dominant, heterozygotes can be identified

• Variation examined close to DNA level

• Provides genetic marker loci for other studies

Motoo kimura

• neutral variation

• most molecular variation must be selectively neutral

• Negative selection rapidly eliminates detrimental mutations

• Positive selection rapidly fixes beneficial mutations

• The only mutations left to create genetic variation are selectively neutral

• DNA sequencing shows that there are a lot of silent mutations that dont affect the genotype but still causues variation

Genetic variation at the DNA level

• differences in the sequence of nucleotides (adenine, thymine, cytosine, and guanine) among individuals within a species

• The genetic code is redundant (or degenerate), meaning multiple 3-letter codon combinations can code for the exact same amino acid. Because of this property, a mutation in the DNA sequence can either change the resulting protein structure or leave it completely unchanged.

Corn and Teosinte - genetic variation

• corn was domesticated from teosinte (like a very small cornt)

• polymorphism of teosinte is higher than in corn

• corn (maize) lost a significant amount of genetic diversity when it was domesticated from its wild ancestor (bottle neck)

• farmers chose limited and specific traits from corn

• The specific genes controlling these desired traits were swept to fixation (meaning almost all corn plants carried the exact same allele), stripping away variation at those genetic loci.

nonsynomous substitution

single-nucleotide mutation in a gene's coding region that alters the resulting amino acid sequence of the encoded protein.

Frequency of fixed differences

• if functional differences between species are driven by natural selection (adaptation) rather than random genetic drift, we should see an unnaturally high number of permanent amino-acid changes in the protein

• if differences are due to genetic drift then there shouldn’t be as many permanent amino acid changes

• this is assessed with the number of polymorphisms within species

• A high number of fixed differences could simply mean a gene mutates rapidly, not that it was adaptively selected.