Genetic Variation, DNA and RNA

Variation

• Variation is essential for evolution and is found everywhere within populations.

DNA, RNA, and Genes

• DNA: The double-stranded genetic material of organisms, arranged around proteins called histones, which help maintain chromosome shape.
• Histones: Influence gene expression by turning genes on or off.
• RNA: Single-stranded, made from DNA, contains uracil instead of thymine.
• Genes: Sequences along a DNA strand.
• Synonymous Change: Genetic changes that result in the same protein product.
• Proteins: Synthesized based on genetic information.
• Promoter Regions: Control sequences adjacent to genes that code for proteins.
• Introns: DNA regions that do not code for proteins.
• Alternative Splicing: Allows different protein variants to be produced from a single gene by removing exons.

Measuring Genetic Variation

• Nucleotide diversity (π): Measures DNA sequence variation between two random individuals.
• Single Nucleotide Polymorphism (SNP): A single position in a DNA sequence with variation (e.g., GGG to GCG).
• Genetic Bottleneck: A sharp reduction in population size that leads to decreased genetic diversity in subsequent generations.
• Humans have low genetic diversity, the result of a genetic bottleneck

Genotypes and Phenotypes

• Phenotypes: Observable and measurable traits influenced by both genetics and environment; natural selection acts on phenotypes.
• Genotypes: Genetic makeup, with different gene versions called alleles located at a specific locus on a chromosome.
• Allele Frequency: How often an allele appears in a population.
• Some alleles are very rare.

Genetic Principles

• Mendel's Law of Segregation: Alleles for a gene separate during gamete formation.
• Hardy-Weinberg Equilibrium: A theoretical state of no genetic change in a randomly mating population.
• Genotype Frequency: How often a genotype occurs in a population
• Gene Frequency: How often a gene occurs in a population
• Law of Mass Action: The rate of a chemical reaction is proportional to the product of the masses of the reactants
• The Hardy-Weinberg equation is p + q = 1 and p^2 + 2pq + q^2 = 1 where p and q are the allele frequencies

Recombination and Linkage Disequilibrium

• Mendel's Law of Independent Assortment: Genes sort into gametes independently of each other.
• Recombination: Combines gene copies from different parents.
• Recombination Rate: Probability of recombination between two loci.
  • Low recombination rate: Genes close together are likely inherited together.
  • High recombination rate: Genes far apart are less likely to be inherited together
• Linkage Disequilibrium: Non-random association of alleles at different loci.
• Recombination reduces linkage disequilibrium.
• D (linkage disequilibrium) = P(AB) - P(A)P(B), where P(AB) is the frequency of haplotype AB, and P(A) and P(B) are the frequencies of alleles A and B.
• Natural selection can drive linkage disequilibrium if certain genes are selected to be inherited together to cause certain phenotypes.

Epistasis

• Situation where different genes interact with each other to affect a given phenotype.
• Linkage disequilibrium can also be affected by the position of alleles on a chromosome, where genes in close proximity to each other tend to separate together.

Sources of Variation

• Phenotypic and genomic variation must differentiate from each other
• Recombination: Creates new gene combinations, associated with sexual reproduction.
• Horizontal Gene Transfer: Bacteria exchange genes.
• Jumping Genes: Insert themselves into an individual's genome; can cause useful variation
• Hybridization: Joining of two genomes, more important in plants.
• Introgression: Acquiring genes through hybridization, becoming part of a lineage until something happens

Mutation

• Mutation: Errors in DNA replication.
• Point Mutation: Single nucleotide change.
  • The 3 positions of codons evolve differently from each other.
  • Any change to the second position of a codon is nonsynonymous
  • Nonsynonymous mutations change the encoded amino acid.
  • Most (but not all) changes to the 1st position are also nonsynonymous
  • Mutations in noncoding genes are important.
• Structural Mutations: Affect more than one DNA base.

Structural Mutations

• Affect an entire chromosome
  • Deletion: Loss of a chromosome region.
  • Duplication: Copying a chromosome region, which can lead to gene evolution.
  • Inversion: A region is copied reversibly and flipped over.
  • Fission: Breaking apart of things; a chromosome copies itself as 2 different pieces
  • Fusion: Chromosomes break apart and recombine at any point.
• Variation in Haploid Chromosome Numbers: Different plants with different chromosomes can copy them and it's not a problem for them
• Mutation Rates: Happen all the time but rare

Features of Mutation

• Pleiotropy: Single gene affects multiple phenotypes.
• Single mutation can affect multiple phenotypes
• Deleterious: Most mutations are harmful with negative effects on fitness and phenotype.
• Low mutation rates.
• Only a small fraction of mutations are useful.
• Transversion mutations
• Random on their effects on fitness
• Most new mutations that affect fitness are deleterious

Non-Genetic Inheritance

• Epigenetic Inheritance: Changes in gene expression without changing DNA sequence.
  • Gene expressed when turned on and doesn't do anything when turned off
  • The environment can cause this.
  • Can go away after a couple of changes
• Maternal Effects: Mothers affect offspring phenotype through genetic and nongenetic effects.
  • Transcended can occur from one generation to the next
  • Don't affect the long term only the short
• Cultural Inheritance: Learned behaviors; cognition has strong genetic effects.

Genetic Theory of Natural Selection

• Selective Coefficient: Measures the fitness reduction of a genotype.
• Industrial Melanism: Example of natural selection where dark-colored (melanic) forms become more common in polluted environments.
  • Melanic: Colored entirely dark, high melanin
  • Typical: Speckled form (good unpolluted)
• Artificial Selection: Selective breeding for human needs.

Evolution by Natural Selection

• Correlation between a phenotypic trait and the number of offspring that bearers of that trait leave in the next generation.
• A correlation between the parental phenotype of a trait and the offspring phenotype.
• Fitness: Number of offspring an individual has.
  • Absolute Fitness: Number of zygotes produced during an organism's lifetime.
  • Relative Fitness: Absolute fitness scaled by a reference, such as mean fitness.

Fitness Components

• Viability: Likelihood of becoming a mature organism.
• Mating Success
• Fecundity

Natural Selection and Allele Frequencies

• Positive selection increases the frequency of alleles with higher fitness until the allele reaches one.
• The spread of three beneficial mutations that have different selection coefficients.
  • a2 allele can become fixed in a population when the allele reaches one, when it's the only gene in a population.

Fisher's Fundamental Theorem

• States that the rate of increase in fitness of an organism at any given time is equal to its genetic variance in fitness at that time.
• If (s) is big then the rate of change will be large, if (s) is small then the rate of change will be small.

Additional selection information

• Δp = sp(1-p)
• Dominance affects the evolutionary trajectories of beneficial alleles.
• Heterozygotes is better than the homozygotes
• Lactase persistence persists in adults and babies.

Adaptation and Change

• Adaption and sex-linked inheritance
• An individual with a good gene has a 50/50 chance of giving that kid the gene, if there are 2 offspring there's a 25 percent chance they won't get it.
• A number of traits that are expressed only in males are located on the male chromosome.
• Lots of stuff that can hinder the spread of a gene.

Hitchhiking

• spread of a gene that occurs if it is associated with another allele that is a target of selection.
• Genetic signature “selective sweep” - when an allele under positive selection tends to be inherited along with other, neutral alleles that are in close proximity to it on a chromosome.

Balancing Selection

• Tends to maintain genetic variation in a population, but it is rare in most species.
• Allele frequency trajectories under three kinds of selection
• Negative frequency-dependant selection maintains a remarkable polymorphism in a fish that feeds on the scales of other fish.
  • The individual doing the less common things has an advantage
  • Fitness and benefits switch.
  • Never lost in population will always be maintained
• Positive frequency independent selection favors whatever color pattern is locally most common in populations of distasteful butterflies
  • Other species evolve similar colors
  • Useful to do the most common thing.
• Selection pushes populations uphill toward adaptive peaks
• Mean fitness- average fitness of the entire population
• Mean fitness increases slowly with no genetic variation.
• Adaptive Peaks really high fitness (combination of Gene A and Gene B)
• Adaptive Values- population has particular variation of gene b and gene a.
• Moves up adaptive peaks
• NS increases the mean fitness of a variation
• Wright's adaptive landscape under the three kinds of selection
• Mutation is associated with selection balance
• Purifying selection: Removes deleterious mutations
• Genetic Load: Measures how much a mutation deviates, a number between 0 and 1

Genetic Drift

• The last surviving wooly mammoths were fixed for many deleterious mutations
• Affects small populations and can cause alleles to become fixed randomly.
• Meiosis: gametes are made and carried by mom or dad, the way those gametes link up is random.
• These random events are impactful when pop is small
• Drift is unbiased for computer simulations
• Random allele frequencies are larger in small populations
• Drift decreases genetic variance
• Drift causes populations that are initially identical to become different
• An allele can become fixed in a population without the action of natural selection

Genetic Drift: Experimental Populations

• N is the population size
• Random genetic drift in experimental populations of Drosophilia melanogaster
• Variation among the population, earlier variation disappears

Genetic Drift: Natural Populations

• Allele frequency differences between two populations of the garden snail is caused by genetic drift
• Snails adapting to different environments across the road, this is bc of genetic drift

Effective Population Size

• All population effect by Genetic Drift
• Only population it doesnt happen to are populations that are too large, even still effected by genetic drift.
• Every population is potentially affected by genetic drift.
• Provides a measure of how prone a population is to genetic drift.
• Bottleneck: Population reduction where not every individual survives.
• Founder Effect: Subset of a population breaks off.
• Measure of Polymorphism
• Genetic variation in humans declines with distance from East Asia
• Amish
  • One of the original founders of the US has been passed on to the rest of the population

Gene Trees

• The evolution of a gene tree
• Coalesce- when 2 genes copies merge
• Trace anything to the founder

Genetic Drift and Variation

• Any 2 humans and compare their genomes and see that they are similar!
• A fair amount of polymorphism
• Much higher genetic variation between genes and within introns than within coding regions
• Background selection:
• Nonsonomous - change amino acid coding form
• Selective constraint- can't be allowed to tolerate mutations, bc mutations are generally bad.
• Nucleotide diversity along the left and right arms of chromosomes 2 and 3 of Drosophila melanogaster is the result of a deleterious mutation

DNA Polymorphism

• Effective population size estimated from levels of DNA polymorphism
• Isn't much genetic variation in the human genome

Population Variation

• Northern and Southern populations
• Arrive in the US from Cuba millions of years ago. Differences in the populations, because of local adaptations. Habitatis are totally different.
• The color of the fur of deer mice is locally adapted to the color of the soil they live on; the wrong color is bad and a difference in one allele
• Fixation index: commonly used to find differences in population, specifically genetic differences.
• Fst is a statistic used to measure genetic differences between two or more populations.
• A lot of variation, it will become large
• Considers the amount of fixation within and between a population

Isolation and Phenotypic Plasticity

• Isolation-by-distance in human populations: As populations become more distant, the greater the difference
• Yarrow is tall in populations near sea level and short in populations at high elevation
• Phenotypic Plasticity: variation due to environmental effects.
• Common garden experiment: eliminate differences in the environment and raise them when they are smaller to adult organisms, and see if there are any differences in the environment, started by having no genetic differences.

Gene Flow

• Results in the mixing of alleles from two populations.
• Dispersal: Where individuals or their gametes move over some distance.
• Friction drag (handing out the car window with the wind is an example of friction drag)
• Some of the ways that plants disperse their seeds

Gene Flow Measurement

• Populations can be in and out of isolation
• Migration rate (m)
• Migration variance

Gene Flow vs Selection

• Gene swamping: homogenizing effect of gene flow overwhelms local adaptation.

Clines

• A gradient of phenotypic or genetic change along a line of environmental or geographic transition.
• Gloger’s rule: is similar but applies

Cline Length

• Tension Zone: can occur when fitnesses at one or more loci are underdominant.
• Gene Flow and genetic drift
• Dispersal- organisms disperse for a variety of reasons, may be favored if the environment changes, or if local competition for resources is intense, or organisms may occupy ephemeral habitats.
• Useful but comes with cost: randomness is involved and can be costly, seeds just end up disappearing or are unuseful, where they can't grow and germinate.

Tradeoffs in Dispersal

• Involve the immune system.
• Dispersal evolved in response to environmental disturbance in a laboratory experiment with the nematode.

Consequences of Dispersal

• Tradeoffs have resulted in morphs (Two different morphs)
• Pika populations have become extinct bc of climate change