Lectures 1 - 4 Flashcards
Why is loss of genetic diversity a problem?
Natural selection theorem - rate of evolutionary change in a population is proportional to the amount of genetic diversity available. Genetic diversity equates to evolutionary potential for response to environmental change. High genetic variation within individuals or populations is positively related to fitness. Global pool of genetic diversity represents all the information for all biological processes on the planet “primary level of biodiversity”.
Why is loss of genetic diversity a problem? (pt2)
Loss of genetic diversity will decrease the ability of organisms to respond to environmental changes, and likely discard information potentially useful to humans. Conservation genetics is motivated by the need to reduce current rates of extinction and to preserve biodiversity.
Why conserve biodiversity?
Food and drink, Medicines, Industrial resources, Ecosystem services, Ecotourism
What is genetic diversity?
Interspecific - diversity hotspots. Intraspecific (within a species): between populations, within a population, within an individual. Genetic diversity is originally generated by mutations in DNA sequence. Genetic diversity within a population may increase via migration/dispersal of gametes. Outbreeding: higher within population variation, Interbreeding: higher between population variation
Why measure genetic diversity?
Document losses of genetic variation. Document evolutionary changes. Document genetic differentiation of populations. Predict changes in the genetic composition of populations
How to measure genetic diversity?
Polymorphism (P): proportion of loci that are polymorphic i.e. loci with >1 allele Heterozygosity (H): proportion of loci that are heterozygous in an average individual Allelic diversity (A): mean number of alleles per locus (depends on the marker type)
Hardy-Weinberg Key assumptions
If large population, mating random, no mutation, migration. Allele frequencies in a population will remain at equilibrium over time. Also assumes Mendelian segregation of alleles, equal fertility of parent genotypes, equal survival of genotypes, equal fertilising capacity of gametes, random union of gametes.
Rare alleles and recessive traits
Most mutations are recessive as it is easier to disrupt the function of a gene than to create a new gain-of-function. They are normally also relatively rare in a population. Thus, for a recessive human disease gene, a heterozygote won’t experience any negative selection pressure. Only the homozygote form will be selected against, but because they are rare, the frequency of the double mutant will be very low. Thus, the mutant allele is maintained in a population by carriers – providing the population is large-enough.
Five agents of evolutionary change
- Mutation 2. Gene flow 3. Non-random Mating 4. Genetic drift 5. Selection
New Mutations
At the moment of formation a new mutation will be heterozygous. Mutation occurs in an exon: Silent mutation, conservative change, non-conservative change. Mutation occurs in the promoter: Can change where/when the protein is expressed
Use of Hardy-Weinberg
Can calculate expected heterozygosity – evolutionary potential depends on genetic diversity. Can see loss of genetic diversity over time by comparing heterozygosities over time. Estimate the frequency of recessive alleles in a large population. Estimate the frequency of carriers in a population. Deviations from H-W allow us to detect inbreeding, genetic drift, migration, selection and loss of diversity
Microsatellite markers = Simple Sequence Repeats (SSR)
Repeats of 2-5 nucleotide sequences – powerful tool for population genetics. High mutation rate gives high levels of genetic diversity – up to 20 alleles per microsatellite. Usually neutral (not normally in coding sequences) – not under direct selection. Coding region SSRs often trinucleotide repeats, corresponding to codon repeats.
Detection of microsatellite allele length using PCR
Need specific primers for each locus, but these can work across closely related species. They are not multiplexed to a high degree, i.e. can only assay a small number of loci in one PCR reaction – low throughput markers.
Different fragment lengths can be separated by:
- Gel electrophoresis 2. Use of fluorescently tagged primers and analysis on a capillary DNA sequencer 3. Or simply identify them from next gen sequence data
Single nucleotide polymosphisms (SNPs)
A site in a DNA sequence that is variable for at least 2 nucleotides (alleles) - the site becomes the locus. Most are bi-allelic. In non-coding regions. Human genome on average 1 major SNP (present in >5% population) every 300 to 1000 bp. Non-synonymous substitutions will change protein sequence - functional variation – possible selection pressure
Genome-wide SNP detection methods include:
Whole genome sequencing – detailed bioinformatics. Transcriptome sequencing – polymorphisms in genes. Genotyping by sequencing (GBS) – high multiplexing. SNP chips - genotyping arrays – simple data analysis.
Genotype by Sequencing - GBS
Robust, simple Genotyping-by-Sequencing (GBS). Approach for high diversity species. No knowledge of genome sequence required. Relatively low cost due to high degree of multiplexing.
How is genetic diversity lost?
Decreasing population size usually results in loss of genetic diversity. Population fragmentation stops flow of genetic material between populations - lack of dispersal. Loss of diversity in domestic species due to agricultural policy, consumer demand and the consequences of breeding strategies.
Why small population size leads to loss of genetic diversity?
More vulnerable to genetic effects: genetic drift, inbreeding, population bottlenecks, Less likely to be able to maintain diversity through gene flow. Evolutionary consequences: Chance dominates, little effect of selection = replicate small populations varying outcomes. “Sitting duck” – vulnerable to not being able to adapt
Effective population size, Ne
To a geneticist, populations are smaller than they seem (Ne is less than N). Ne is the size of an idealised population that would lose genetic diversity at the same rate as the population being considered. Genetic diversity is lost as Ne declines, not just N.
Genetic drift
Each generation derived from a sample of parental gametes. Allele frequencies fluctuate/drift from one generation to another. Effect more pronounced in smaller populations.
Genetic drift has major impacts on evolution of small populations
Allele frequencies change over generations. Diversification of allele frequencies. between fragmented populations. Loss of genetic diversity = fixation. Can overpower natural selection. Some alleles go extinct or become fixed.
Fixation
Genetic drift ultimately causes loss of diversity through fixation, all but one allele is lost. Prob of losing an allele = (1-p)^(2N). Therefore rare alleles more likely to be lost. Alleles more likely to be lost in small pops
Population bottlenecks
Sharp reduction in pop size (short or long term). Reduces genetic diversity (even if population recovers). Time spent as small population also reduces genetic diversity.
