University of Queensland ANIM 2503 Animal Breeding and Molecular Genetics Review Lecture for Quiz 2 2022 PDF

ANIM 2503 ANIMAL BREEDING AND MOLECULAR GENETICS SEMESTER 2, 2022 REVIEW LECTURE FOR QUIZ 2 PREPARATION DR LEE MCMICHAEL UNIVERSITY OF QUEENSLAND, GATTON CAMPUS SCHOOL OF VETERINARY SCIENCE [email protected] On Blackboard in your Assessment Folder • Browser recommendation • Technical issues d...

ANIM 2503 ANIMAL BREEDING AND MOLECULAR GENETICS SEMESTER 2, 2022 REVIEW LECTURE FOR QUIZ 2 PREPARATION DR LEE MCMICHAEL UNIVERSITY OF QUEENSLAND, GATTON CAMPUS SCHOOL OF VETERINARY SCIENCE [email protected] On Blackboard in your Assessment Folder • Browser recommendation • Technical issues during Inspera assessments: DO NOT close your browser. Collect evidence of the issue. Contact AskUS on +61 7 3346 4312 (or at https://web.library.uq.edu.au/contact-us) immediately • Assessmment quiz link will become visible in assessment folder at 7:30 am AEST on quiz day, quiz opens 8 am and closes 9 am • Student with approved assessment adjustments have been contacted and can go to Assessment folder to find the link to login for your adjusted quiz time now. Contact me if you should have adjustment and this is not visible to you. [Presentation Title] | [Date] CRICOS code 00025B 2 Epigenetics CRICOS code 00025B 3 Epigenome: • Chemical compounds and proteins that attach to DNA and regulate gene expression, for example, turning genes on or off. • Control the production of proteins in particular cells but do not change the sequence of the DNA, but changes gene expression Epigenetics: • The study of heritable changes in gene function that cannot be explained by changes in gene sequence CRICOS code 00025B 4 Types of Epigenetic Changes DNA methylation: Addition of a methyl group to the 5-position of the cytosine ring. Methyl groups project into the major groove of DNA, inhibiting transcription. • Hypermethylation of silences genes • Hypomethylation can activate gene expression Post-translational histone modifications: Histones H3 and H4 have aminoterminal tail that protrudes from nucleosome which can be covalently modified. Modifications include – acetylation, methylation, phosphorylation plus others. • Histone acetylation → gene activation • Histone deacetylation → gene repression MicroRNAs and RNAi: microRNAs or miRNAs degrade many mRNAs to repress translation. Small interfering RNA or siRNAs are specific to a mRNA sequence and leads to cleavage. CRICOS code 00025B 5 Imprinted Genes • Male and female gametes have different epigenetic modifications • Imprinted gene is silenced • Thus only one allele is expressed in offspring • Which allele is expressed depends on parent-of-origin • Different phenotypic combinations can occur depending on imprint pattern, thus a heterozygote may indeed express a recessive allele if the dominant allele is silenced From: https://www.sciencedirect.com/t opics/medicine-anddentistry/paternal-inheritance CRICOS code 00025B 6 MHC Genes CRICOS code 00025B 7 Major Histocompatibility Complex of genes The major histocompatibility complex (MHC) is a large number of closely linked polymorphic genes on vertebrate DNA that code for cell surface MHC proteins essential for the adaptive immune system Diversity of an individual’s expression of MHC genes is attained in at least three ways: • An individuals MHC repertoire is polygenic (multiple interacting genes) • MHC gene variants are highly polymorphic (diversely varying from organism to organism within a species) • MHC expression is codominant (from both sets of inherited alleles) CRICOS code 00025B 8 MHC Polymorphisms • The products of individual MHC alleles can differ from one another by up to 20 amino acids, making each variant protein quite distinct. • Most of the differences are localized to exposed surfaces of the outer domain of the molecule, and to the peptide-binding groove in particular. • MHC polymorphism appears to have been strongly selected by evolutionary pressures with powerful mechanisms for generating the variability on which selection can act. • Several genetic mechanisms contribute to the generation of new alleles inclusive of point mutations and recombination • The effects of selective pressure in favour of polymorphism can be seen clearly in the pattern of point mutations in the MHC genes. Non-synonymous substitutions occur within the MHC at a higher frequency relative to silent substitutions than would be expected, providing evidence that polymorphism has been actively selected for in the evolution of the MHC. CRICOS code 00025B 9 Importance of MHC genetic variability MHC variants influence many important biological traits: - immune recognition - susceptibility to infectious and autoimmune diseases - mating preferences - kin recognition - cooperation Diverse functions and characteristics place MHC genes among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection CRICOS code 00025B 10 Outbreeding versus inbreeding populations • In large outbred populations, polymorphism at each locus can potentially double the number of different MHC molecules expressed by an individual, as most individuals will be heterozygotes. • Polymorphism has the additional advantage that individuals will differ in the combinations of MHC molecules they express, therefore present different sets of peptides from each pathogen. • This makes it unlikely that all individuals in a population will be equally susceptible to a given pathogen and its spread will therefore be limited. CRICOS code 00025B 11 MHC genes in population genetic studies • Genetic studies of wild animals often employ neutral markers e.g. mtDNA, microsats, SNPs to estimate the amount of variation within and between populations. • Useful for phylogenetic reconstructions and population history but the variation at neutral loci cannot provide information on selective pressures on individuals from their environment or the populations capacity for adaptive change. • MHC markers are valuable as they are highly variable and under selective pressure, while neutral genes may not show changes when the time span between the separation of populations is too short • MHC variability reflects evolutionary relevant and adaptive processes within and between populations and is very suitable to investigate a wide range of open questions in evolutionary ecology and conservation. CRICOS code 00025B 12 Antibiotic Resistance CRICOS code 00025B 13 How does antibiotic resistance occur? CRICOS code 00025B 14 [Entity Name] [Presentation Title] | [Date] Mechanisms of Resistance https://amrls.umn.edu/microbiology CRICOS code 00025B 15 Bacterial transformation: Horizontal gene transfer by which some bacteria take up foreign genetic material (naked DNA) from the environment. It was first reported in Streptococcus pneumoniae by Griffith in 1928. Bacterial Transduction: Horizontal gene transfer by which foreign DNA is introduced into a cell by a viral vector. It is DNase resistant where transformation is susceptible to DNase activity). Bacterial Conjugation: Horizontal transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells. This takes place through a pilus. Image: http://www.nature.com/nrmicro/journal/v4/n1/images/nrmicro1325-f2.jpg CRICOS code 00025B 16 Horizontal gene transfer via Plasmids Continually replicated within the bacterial cell Can spread resistance genes to other microbes Incredibly important and fascinating aspect of bacterial evolution Donor cell produces pilus. Pilus attaches to recipient cell, bringing cells together. Mobile plasmid is nicked and a single strand of DNA is transferred to the recipient cell. Both cells synthesize a complementary strand to produce a double stranded circular plasmid and also reproduce pili; both cells are now viable donors. Image: http://www.scienceprofonline.com/images/Conjugation.png CRICOS code 00025B 17 Gene Discovery and Therapy CRICOS code 00025B 18 Two broad categories of Genome Wide Studies: Linkage vs Association We have two options for trying to predict phenotypes from genotypes Linkage studies use pedigrees and look for evidence of recombination in meiosis - Need information from family members (ideally across several generations) - Useful for simply inherited traits Genome Wide Association studies use allele frequency differences between groups of unrelated cases and controls - Need information from affected individuals and matched controls (unaffected) - Useful for simply inherited and for more complex multifactorial traits CRICOS code 00025B 19 GENOME WIDE STUDIES How do we identify genetic variants if we don’t know where the variants might be? We use an approach that scans the whole genome. All Genome Wide techniques rely on the follow underlying principles: • Groups of markers (SNP/microsatellite) and genes co-segregate with disease phenotype in a pedigree • The chances of recombination between two markers depends on the distance between them CRICOS code 00025B 20 Calculating distances to the disease locus • Genetic distance (cM) = number of recombinant progeny divided by total number of progeny as a% • Don’t count those that came from outside this genetic lineage! • A/G marker locus doesn’t ‘cause’ the disease, but it may be ‘near’ the causative locus AG AG • What is the genetic distance between the disease locus and this A/G locus? GG Not part of genetic lineage; don’t count GG GG * AG AG GG * GG AG AG * • 5/10 = 0.5 cM (centiMorgans or recombination units) SNP101 AG * CRICOS code 00025B 00025B GG * GG Putting recombinant distances from multiple loci into a map • We know where SNPs are located on the chromosomes • Compare distances for loci : A G SNP101 A T SNP102 T C SNP103 • SNP101 A/G = 0.5 • SNP102 A/T = 0.1 • SNP103 C/T = 0.1 • Determine where disease locus is on map: Disease locus Typical to map > 170,000 SNP loci CRICOS code 00025B 00025B Narrowing down on the causative mutation • Once we know the region of the chromosome where the disease mutation is, we can either: • Utilise the marker with high linkage in an indirect genetic test (without finding the true causative marker); or • If there is a whole genome sequence available, look at candidate genes in the vicinity of the marker - Likely genes, i.e. ones with relevant function, can be sequenced in affected and normal individuals to identify the mutation CRICOS code 00025B 00025B CANDIDATE GENE ANALYSIS PRINCIPLES • Biological pathways are relatively conserved across species • If we know the genes involved in the pathway that is not functioning correctly, then we can sequence those genes and find the mutation • Need to have some knowledge (or an educated guess) of the pathways and genes involved • Need to know sequences of genes (or take educated guess) for primer design if using PCR and sequencing • Often relies on similarities across species = comparative genomics CRICOS code 00025B 24 Approaches to gene therapy Gene delivery: a normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene Gene repair: the abnormal gene could be repaired, which returns the gene to its normal function • An abnormal gene could be swapped for a normal gene through: - Homologous recombination - CRISPR-cas9 Gene regulation: the regulation of expression of a particular gene could be altered CRICOS code 00025B 00025B Gene delivery therapies • Exogenous gene introduced and must either • Integrate into the patient’s genome or • Exist as a stable replicating episome (genetic element that can replicate independently of the host) • For long term expression it is more efficient to target stem cells • Needs to be safe and efficient • Approaches can be classified into one of two categories: • In vivo (direct) • Ex vivo (cell-based) CRICOS code 00025B 00025B In vivo gene delivery Ex vivo gene delivery http://stemcells.nih.gov/info/2006report/2006Chapter4.htm CRICOS code 00025B 00025B In vivo Ex vivo • Advantages • Advantages • Cheaper than other methods - No culturing of cells needed • Potentially easier than other methods • Disadvantages • Requires much more testing and refinement • Safety concerns for gene therapy - If something goes wrong, it may be difficult to reverse the process • Select for the modified cells, thereby increasing efficiency • Monitor expression levels before cells are returned to the patient • Monitor for any undesirable characteristics in the modified cells • Because cells are autologous, there is very little chance of rejection by the host immune system • Disadvantages • Only applicable to those cells that can be readily removed from a patient, grown in culture and reintroduced - Skin cells and haemopoietic cells are ideal CRICOS code 00025B 00025B Delivering genes to the right area DNA or mRNA needs to be delivered to the cells: 1. Viral delivery • Lentivirus (retrovirus) • Adenovirus, Adeno-associated virus, Herpes simplex virus 2. Other delivery mechanisms • Lipid nanoparticles e.g. liposomes: artificial lipid sphere with phospholipid and cholesterol bilayer membrane – fuses/penetrates cell membrane or uptake by endocytosis • Biodegradable polymers, exosomes: taken into cell by endocytosis • Injection and spontaneous uptake • Receptor-mediated transfer CRICOS code 00025B 00025B Gene repair: Homologous recombination • Uses cellular DNA repair process for double-strand break (see DNA damage and repair lecture) 1. Therapeutic gene added to a copy of the targeted genomic DNA region in vitro 2. Recombinant DNA is transfected into the cells using a vector 3. The modified copy recombines with the homologous part of the cell’s genome 4. Edited (recombinant) cells given back to the patient • Advantages • Puts gene of interest into a defined region of the genome • Circumvents positional effects and gene silencing mechanisms • Disadvantages • Homologous recombination is rare (when fragment is introduced to mammal cells, the frequency that it is incorporated in a homologous fashion is one recombinant per one million cells) • Need to use some mechanism to allow cells in culture that have recombined in correct position CRICOS code 00025B 00025B to be selected over non- recombinant cells Gene Repair: CRISPR-cas9 • Bacteria have an innate immunity system to protect against viruses • Clustered Regularly Interspaced Short Palindromic Repeats – CRISPR • Series of repeat and spacer regions • Encodes RNA • Forms a complex with cas – enzymes that cut dsDNA - This enzyme is used by bacteria to defend against invading viruses by cutting their DNA 1. Short RNA guides (~20bp) designed to match target 2. The complex locks onto target by inserting between strands of DNA 3. cas enzyme cuts dsDNA at the right position 4. Various end joining mechanisms used to repair defective gene • Has advantage of changing DNA at a specific site; but off-target effects identified (RNA guide might match multiple sites) CRICOS code 00025B 00025B Gene regulation therapies • RNAi – small RNA molecules that affect gene expression • Important part of normal pathways in eukaryotes for regulating abundance of mRNAs • small interfering RNA or siRNAs; specific to mRNA targets (see Epigenetics lecture for details) • Synthetic siRNAs can be used for gene regulation therapy https://ai2-s2-public.s3.amazonaws.com/figures/2017-0808/9d5bd5b91b80f2ce110e8e6b221a94236a151857/2-Figure1CRICOS code 00025B 1.png Phylogenetics CRICOS code 00025B 33 Phylogenetics • Phylogenetic trees are part of the standard toolbox of genetic data analysis • Phylogenetic tree or evolutionary tree is a branching diagram showing the evolutionary relationships among various biological species based upon similarities and differences in their genetic code. CRICOS code 00025B 34 Describing Trees CRICOS code 00025B Outgroups and Tree Roots CRICOS code 00025B Phylogram versus a Cladogram Phylogram is a phylogenetic tree that has branch spans proportional to the amount of genetic change Cladogram is a phylogenetic tree that represent relationships between organisms showing which have common ancestors CRICOS code 00025B 37 Difference between individuals based on assessment of DNA Mutations CRICOS code 00025B Distance-based methods: Calculate genetic distance from multiple sequence alignments Most take into account only the total number of mutations, e.g. Neighbour Joining Character-based methods: Reconstructing evolutionary changes throughout the tree Take into account both the number and the types of mutations, e.g. Maximum Likelihood, Maximum Parsimony, Bayesian CRICOS code 00025B Distance Trees In this tree, the branches are drawn proportionally with the genetic distance so the tree can be referred to as a phylogram. The scale shows the distance associated with sequences that are 5% divergent, that is 5 differences per 100 nucleotides. CRICOS code 00025B Reliability of trees Several measures of reliability – Distance/Parsimony: Bootstrap values – Maximum likelihood: Likelihood values – Bayesian: Posterior probabilities Higher values (>70%) indicate reliability Values <50% generally not shown CRICOS code 00025B • Note bootstrap value • Is the tree reliable? • Is the tree rooted? • Are humans carrying zoonotic strains? • What do shorter branch lengths tell us about rate of change? CRICOS code 00025B Parentage Analysis CRICOS code 00025B 43 Why do we need to identify individuals • Thoroughbred and purebred parentage testing • Livestock breeding programmes • Conservation-based breeding programmes • Assessing genetic diversity, population size or illegal trade of at-risk populations • Tracing sources of infection • Linkage analysis CRICOS code 00025B 44 How do we identify individuals The DNA fingerprint for individuals is unique (except for identical twins). Need multiple DNA markers that mutate rapidly (i.e. highly polymorphic). Two options for marker choice: • Few markers that each have many possible alleles • Large number of markers that each have only a few possible alleles Concept of Probable Identity: What is the probability that two individuals drawn at random from the population have the same genotype across multiple loci? ie the probability that a pair of individuals will match at a specific number of loci. CRICOS code 00025B 45 Interpretation of DNA Parentage Analysis At every locus, offspring inherits one allele from its sire and one allele from its dam (simple Mendelian inheritance) • If allele is common, it is possible (or probable?) that two individuals will share an allele by chance, not descent • Use multiple loci (multi-locus genotype or ‘fingerprint’) • Perform Parentage by Exclusion – if potential parents don’t share an allele at each locus of the offspring, they cannot be the parent CRICOS code 00025B 46 Interpreting Parentage Results Based on Mendelian inheritance: ➢An offspring must have one allele from the sire and one allele from the dam ➢In reality, use many more loci than this ➢Can perform analysis using SNP or microsatellite IDs or “fingerprints” Need to ask the questions: ➢ Can the mother contribute one allele at each locus to the offspring? ➢ Can the father contribute one allele at each locus to the offspring? ➢ Does the mating qualify? ➢ Use “exclusion” language CRICOS code 00025B 47 Example microsatellite and SNP parentage tables: Individuals Locus 1 Locus 2 Locus 3 Female 180 180 136 138 200 208 Offspring 180 180 132 136 200 208 Male 180 184 128 132 204 208 Male 2 180 180 138 136 200 212 Very common alleles at Locus 1 are not useful for discriminating individuals Both males are possible fathers based on Locus 3 Both males are possible fathers based on Locus 2, Individuals Locus 1Locus 2Locus 3 Female AC CC GT Offspring CC CT GT Male 1 AC TT GG Male 2 AA CT TT BUT only one shows mating qualification (only one parent can provide the 132, mother provides the 136. CRICOS code 00025B 48 Conservation and Population Genetics CRICOS code 00025B 49 Population Genetics Population Genetics is the study of how genetic variations in a population of individuals change under the influence of • Systematic forces (e.g. selection, either natural or artificial) • Random forces (e.g. mutation, genetic drift) The discipline of population genetics is predominantly concerned with changes in allele frequencies in a population To control disease, or improve animal/plant production or conserve a population, we need to be able to manipulate ‘allele’ frequencies at a population level CRICOS code 00025B 50 Genetic variation reflects ‘health’ of populations Variability gives populations the ability to respond to different environments and adapt to changing conditions Low levels of variation can imply: Lower resistance to pathogens Reduced fitness Problems in distinguishing kin from non-kin CRICOS code 00025B 51 Conservation of Threatened Species Many species are at the risk of population shrinkage >> extinction due to natural factors (climate, genetic drift, mutations) and human interference Small population size may lead to lower genetic fitness through fixation of deleterious alleles and loss of genetic diversity for fitness traits An effective population size of breeding males & female is needed to maintain the present state of genetic diversity CRICOS code 00025B 52 Forces that alter allele frequencies alter genetic diversity Migration Mutation Natural Selection Inbreeding Small populations Random genetic drift Genetic bottlenecks Founder effects Increase diversity Mutation counteracts loss of variation due to genetic drift or selection. But accumulate slowly and usually genetic drift causes loss of variation more rapidly than mutations can counteract, especially in small populations! Decrease diversity Population size plays an important role in modulating loss of diversity. Thus factors that influence population size can therefore impact diversity. CRICOS code 00025B 53 Genetic factors that cause population shrink • Genetic drift: a gradual shift in the gene frequencies of small populations resulting in different genotypic ratios - Random genetic effect – chance event - Founder effects – choice of selecting the parents - Population bottlenecks – natural or artificial causes • • • • Fragmentation - loss of genetic diversity within populations Deleterious mutations – loss of fitness and survival Non-random mating Emigration CRICOS code 00025B 54 Random Genetic Drift Random changes in allele frequency over time Random chance mechanisms include: • Sampling error during gamete segregation • Non-genetic effects on reproductive ability or survival (demographic stochasticity .. Births and deaths causing population size fluctuation) Can lead to loss or fixation of some alleles • Affects all populations, but more severe in small populations CRICOS code 00025B 55 Take home message: Loss of heterozygosity is faster in smaller populations CRICOS code 00025B 56 Impacts of migration on heterozygosity of populations The degree of gene flow depends on migration rate, population size, selection and mutation rates Reduced migration leads to: • A lack of effective gene flow • Genetic divergence between populations Determining how populations are structured tells us: • How divergent are populations • How much gene flow (effective migration) is occurring? CRICOS code 00025B 57 Different populations change in different ways Speed and direction of change of alleles depends on • Relative fitness values of the genotypes • Frequencies of alleles • Whether alleles are dominant or recessive • Genetic drift CRICOS code 00025B 58 How can genetics minimise extinction • Resolve taxonomic uncertainty • Resolve population structure • Define management units • Identify populations of conservation concern • Detect and minimize inbreeding and loss of genetic diversity • Detect and minimize hybridization • Identify best population for conservation programs >>> reintroduction CRICOS code 00025B 59 Conservation methodologies Ex Situ (out of habitat) • • • • • Zoos Aquariums Captive Breeding Botanical Gardens DNA/Gene, seed, tissue banks • Challenges to Ex Situ • Expensive > sustainability • Inbreeding > genetic disorders • Lack of developing natural adaptation • Adaptation to captivity – hard to reintroduce into their natural habitat CRICOS code 00025B 60 Conservation methodologies • In Situ (in a habitat) • Managing habitat loss and degradation • Restoring habitat • Establishing reserves • National parks, Parks Sanctuaries, Rainforests • Challenges of In Situ • Hunting • Natural factors • Inability to find suitable habitat • Inability of individuals to survive/breed CRICOS code 00025B 61 Hardy Weinberg Equilibrium and Selection CRICOS code 00025B 62 What are the Genotypic Frequencies? AA = homozygous dominant = Chesnut = CC = 361/500 = 0.72 Aa = heterozygous = Palomino = Cc = 128/500 = 0.26 aa = homozygous recessive = Cremello = cc = 11/500 = 0.02 CRICOS code 00025B Sum =1 63 What are the Allelic Frequencies? N = 500 Horses in total Therefore have 1000 alelles Frequency of dominant allele = p Frequency of C = p = (2 x nAA) + (1 x nAa) = (2 x 361 + 1 x 128)/1000 = 0.85 Frequency of recessive allele = q Frequency of c = q= (2 x naa) + (1 x nAa) = (2 x 11 + 1 x 128)/1000 = 0.15 CRICOS code 00025B 64 Using HWE to calculate genotype and allele frequencies Genotype frequencies: p2+ 2pq + q2= 1 Allele frequencies: p + q = 1 q2= 0.23 q = √0.23 = 0.48 What is p? p + q = 1, so p = 1 –q = 0.52 Freq BB (p2) = 0.522 = 0.27 Freq Bb (2pq) = 2 x 0.52 x 0.48 = 0.5 CRICOS code 00025B 65 Punnett squares to predict genotype frequencies CRICOS code 00025B 66 Predicting the fate of genotypes over time CRICOS code 00025B 67 Departures from HWE Departures from HWE Departures from HWE indicate at least one of the assumptions has not been met: • Population is too small • More than one population • Migration into or out of the population • Mutation occurs • Selection occurs If population is in HWE, genotypic frequencies will be in proportions p2, 2pq and q2 CRICOS code 00025B 68 Fitness (ω) How much better one phenotype / genotype is able to survive and reproduce in that environment than another • Relative abilities of genotypes to pass alleles to next generation • Ranges from ω = 0 (lowest fitness) to ω = 1 (highest fitness) • Measure ω of a genotype = # progeny / # progeny of most fertile genotype Selection coefficient (s) Relative intensity of selection against a genotype s=1–ω S ranges from 0 (not being selected against) to 1 (strongest selection against) Thus as fitness (ω) increases, selection coefficient (s) decreases. CRICOS code 00025B 69 Darwin’s Finches: an example of natural selection Common ancestor 2M years ago …. Over time speciated into 15 species. Different beak shape evolved to suit different food resources. Some individuals have trait that is better adapted to the environment, thus they survive and produce more offspring than those without the trait If adaptive trait has a genetic basis, its frequency will increase in the next generation CRICOS code 00025B 70 Selection against recessive phenotypes • At strongest selection pressure (s = 1) all affected phenotypes are removed • All homozygotes for the recessive allele are lethal • But the recessive allele remains in the heterozygotes CRICOS code 00025B 71 Selecting against dominant phenotypes • At the strongest selection pressure (s = 1), homozygotes for the dominant allele AND heterozygotes will be removed • Completely removes the dominant allele from the population in one generation CRICOS code 00025B 72 Selecting against a recessive allele When s < 1, frequency of recessive phenotypes drops slowly when recessive allele is rare (somewhat “sheltered” by heterozygotes) and rapidly when it is common (many homozygotes) Time CRICOS code 00025B 73 Selecting for dominant phenotypes Time CRICOS code 00025B 74 Selecting against dominant phenotypes Time CRICOS code 00025B 75 Can we remove unwanted alleles entirely? Cannot entirely remove an allele from a population due to heterozygote carriers q=0 would mean only dominant alleles remain q=1 would mean only recessive alleles present Not possible Time CRICOS code 00025B 76 • Allele frequency (q) will be higher for recessive deleterious alleles than for partially dominant alleles (when 0 < h < 1) due to heterozygous protection of recessive alleles • Even weak selection against partially dominant allele keeps it at low frequency CRICOS code 00025B 77 Overdominance (e.g. heterozygote advantage) • Also called ‘heterosis’ or ‘balancing selection’ • Leads to stable, balanced polymorphism (alleles in equal frequencies) • Not in Hardy-Weinberg equilibrium (too many heterozygotes) • Relatively uncommon, but can be effective at maintaining variation • Relative fitness of homozygotes is low • Sometimes seen in conjunction with temporal or spatial changes in fitness or via host-parasite interactions • Example is MHC genes or hemoglobin genes CRICOS code 00025B 78 The mutation –selection balance • Suppose there is selection against a deleterious allele (a) • Eventually the allele may be lost from population, but new deleterious alleles arise by mutation • Leads to a balance between: What goes in: mutation (μ) What goes out: selection (s) • The frequency of a is an equilibrium between the rate deleterious alleles are creating in the population by mutation versus removal of the allele due to selection Equilibrium frequencies depend on Selection coefficient (s); Mutation rate (µ) ; Degree of dominance (h) • • where h = 1 represents complete dominance and h = 0 represents completely recessive CRICOS code 00025B 79 Ensure you … Understand the basic principles of each of the lecture topics Perform calculations and interpretations of • • • • • Gene Linkage Parentage analysis Phylogenetic trees Genotypic and allelic frequencies Fitness and selection coefficient CRICOS code 00025B 80