Mutation and Variation Among Individuals PDF

Chapter 5: Mutation and Variation among individuals Three sources of variation  Genetic  Environmental  Genotype-by-Environment Interaction Genetic Variation  Phenythiocarbamide (PTC)  Bitter flavors- TAS2R38 gene on Chromosome 7  Two alleles  PAV ...

Chapter 5: Mutation and Variation among individuals Three sources of variation  Genetic  Environmental  Genotype-by-Environment Interaction Genetic Variation  Phenythiocarbamide (PTC)  Bitter flavors- TAS2R38 gene on Chromosome 7  Two alleles  PAV  AVI  May be associated with ability to detect toxins Genetic Variation Environmental Variation  Traits that are not genetically controlled  Not heritable  Phenotypic Plasticity  Includes inducible defenses Hesse et al. 2012. Fighting parasites and predators: How to deal with multiple threats? BMC Ecology. Genotype-by- Environment  Interaction Aversion to cilantro linked to several genes  Only ~4% higher frequency of hating cilantro among people with two copies of this gene vs. people with zero copies (15% vs. 11%)  Conclusion: aversion is only partly genetic  Could also be driven by environment, or interactions between genotype and environment.  How do we test? Genotype-by-Environment Interaction  Ability to display phenotypic plasticity may be genetically controlled  With no phenotypic plasticity or genotype-by-environment interaction the phenotype is the same in different environments  Reaction norm = phenotypic expression of a single genotype across a range of environments Phenotypic Plasticity  Steepness of slope on reaction norm graph indicates amount of plasticity of that genotype Plasticity vs. Gene-by- Environment Interaction  If plasticity varies among genotypes in different environments, evidence for G x E interaction Genotype-by-Environment Interaction Environmental sex determination Mutation  Raw material of evolution  Without mutation, no new alleles, new genes, and no evolution  Examine how mutations occur so that we can understand how they lead to evolution Where New Alleles Come From  DNA  Made up of deoxyribose sugar, phosphate group, and nitrogenous base  4 Bases  Purines  Guanine  Adenine  Pyrimidines  Thymine  Cytosine The nature of mutation  DNA replicates itself with the help of DNA polymerase  Complementary base pairing  Sometimes the wrong bases will be paired  Sometimes they get corrected  Sometimes they don’t  This results in a point mutation  p78 Nature of mutation  Normal pathway is DNA --> mRNA --> protein  Mutation may affect amino acid sequence  Redundancy of genetic code  Not all point mutations cause changes in proteins Nature of mutation  Transitions  Change from purine to purine or pyrimidine to pyrimidine  Transversions  Change between purine and pyrimidine  Transitions are at least twice as common in nature Nature of mutation Nature of mutation DNA mutations within coding regions (= exons) are either synonymous or nonsynomomous  Synonomous = silent  Does not change amino acid sequence  Nonsynonomous = replacement  Changes amino acid sequence Synonymous vs. nonsynonymous DNA1 = AAA GCT CAT GTA GAA DNA2 = AAG GCT GAT GTA GAA Protein1 = Lys Ala His Val Glu Protein2 = Lys Ala Asp Val Synonymous Nonsynonymous Glu mutation mutation Types of mutations  Frameshift mutations  Where nucleotides in the DNA sequence are added or deleted, creating a change in the reading frame for the protein encoded by the gene  Nonsense mutations caused by point mutation to stop codon Various types of mutations Where do new genes come from?  Gene duplications  Result from unequal crossing over  Extra copy is free to accumulate mutations  Not under natural selection Where do new genes come from?  Gene duplication in globin gene family  Humans have two globin clusters of loci: a-like and b-like  We need two subunits from each cluster to form the hemoglobin molecule  During embryonic, fetal, and adult stages different chains are made Where do new genes come from?  Gene duplication in globin gene family  Adult: a and b  Embryonic: z and e  Fetal: a and g  Different globin family loci produced by past gene duplication events  Took on new functions over time  Some gene copies have also become pseudogenes (= what? How does this happen?) Where do new genes come from?  Gene duplication in globin gene family Where do new genes come from? Paralogous: Genes that duplicated and diverge in a species (e.g. α and β in humans) – may have different function. Orthologous: Genes that are homologous and evolved from a common ancestral gene by speciation (β in humans and β in mouse)  Where do new genes come from?  Retroposition  Processed mRNA is inserted into genome  Chondrodysplasia in dogs Chromosomal alterations  Inversions  Segment of DNA is cleaved in two places, the excised segment flips, and re-anneals in the opposite direction Chromosomal alterations Inversions  Can disrupt linkage  Phenomenon where genes near each other are inherited in groups  Cannot align properly with homologs  Results in dysfunctional gametes  Chromosomal – 5 of 6 Drosophila chromosomes are polymorphic for alterations inversions – Inversion frequencies vary along a cline Linked to temperature and body size – Example: chromosome inversion polymorphism in Drosophila pseudoobscura  Chromosomal alterations  Polyploidy  Entire extra sets of chromosomes  Tetraploid, octoploid, hexaploid, triploid, etc.  Common in plants and rare in animals  Common in hermaphroditic species that can self-fertilize  Chromosomal alterations  Polyploidy  Meiosis error creates diploid gametes  Those organisms self or fuse with other diploid gametes and make tetraploid offspring  If two tetraploids mate, a new species is created triploid tetraploid hexaploid octoploid Chromosomal Alterations  Polyploidy  If a diploid gamete fuses with a haploid one, triploidy results  Triploids have low fertility  Unless they are parthenogenetic  The polyploid organisms have whole chromosomes of genes that are free from natural selection  Creation rate of polyploid plant species is as common as point mutation rate  Unisexual triploid salamanders. Some animal populations are all female. One example is triploid populations of Ambystoma salamanders. They maintain triploidy by using sperm from a male of another species to activate their eggs, after which the sperm nucleus is eliminated. Thus, unisexual salamanders steal sperm from donors of normally bisexual species, and their reproductive mode is described as kleptogenesis. Bogart et al. 1989. Temperature and sperm incorporation in polyploid salamanders. Science 246:1032-4. Nature of mutation Fitness effects of mutations:  Usually neutral  Sometimes beneficial  Sometimes deleterious  Sickle cell anemia  Caused by a single transversion in hemoglobin gene Mutation rates Best data on mutation rates are from loss-of- function mutations – Mutation deactivates gene and causes protein not to be made – Not always easy to identify gene(s) causing problems: why? Mutation rates Best data on mutation rates are from loss-of- function mutations – Some known human examples: Hemophilia Achondroplasia – Dominant condition – Can assess spontaneous mutation rate » Nine out of ten dwarf children have normal parents Mutation rates  Loss-of-function mutations caused by  Point mutations  Insertions  Deletions  Transposable genetic elements  10% of all human gametes carry a phenotypically detectable mutation  Genes within a species vary in mutation rate Mutation rates Modern genomic methods allow the assessment of mutation rates more directly Mutation rates  Why are mutation rates variable?  DNA polymerase varies in error rate  Mismatch repair systems vary in effectiveness  Some species have higher or lower mutation rates overall  Viruses: high mutation rate  Drosophila: low mutation rate  Codingregions have fewer mutations than noncoding regions  Naturalselection (specifically, purifying selection) Measuring genetic variation in natural populations  Traditionally, biologists believed that allelic variation was low within populations  Variations from “wild type” are rare  We now know that genetic variation is incredibly high  We know this due to huge advances in methods for directly measuring genetic and even genomic diversity Determining genotypes  For some loci, we can know genotypes by examining phenotypes  e.g. Achondroplasia  For others, we need to look directly at proteins or DNA sequences  Gel electrophoresis Determining genotypes  Gel electrophoresis  DNA and proteins have charge  Apply electric current to samples and they migrate toward oppositely charged pole  Migrate according to size and mass  Differently sized alleles go different distances Variation in DNA Determining genotypes  Human gene CC-CKR-5  Encodes for CCR5 cell surface protein receptor on helper T cells  When receptor senses pathogens, informs killer T cells to attack  HIV-1 uses CCR5 as coreceptor to bind with CD4 T cells Determining genotypes  Human gene CC-CKR-5  If homozygous dominant (+/+) they can be infected  If homozygous recessive (D32/D32) they cannot be infected  If heterozygous (+/D32) they can be infected but progress to AIDS more slowly Calculating allele frequencies  To determine how common an allele is can calculate its frequency  For example, 43 Ashkenazi people were tested  26 were wild type  16 were heterozygous  1 was homozygous recessive  What does this tell us? Calculating allele frequencies  86 allelic copies  18 were D32  16heterozygotes (= 16 copies of D32) 1 homozygote (= 2 copies of D32)  18/86 = 0.209 or 20.9%  Other races and/or nationalities have much lower rates of D32 alleles Calculating allele frequencies  86 allelic copies (43 individuals)  68 were +  16 heterozygotes  52 homozygote  68/86 = 0.791 or 79.1%  Frequencies of the two alleles always add to 1 – good way to check your math  Calculating allele frequencies Allele frequencies Genotype frequencies AA Aa aa aa aa Aa AA Aa aa aa aa Aa Aa AA Aa Aa Aa Aa Aa AA Aa Aa Aa Aa Aa Aa AA Aa AA aa Aa Aa AA Aa AA aa Aa AA Aa Aa Aa Aa Aa AA Aa Aa Aa Aa AaupAa -Add AA all the Aaa’sAA aa A’s and Aa -Add AaAA’s, up the AA Aa’sAa AA aa and aa’s -Divide each by the total number of -Divide by the number of genotypes alleles (A + a) (=individuals) -A/(A +a) = frequency of A -AA/(AA + Aa + aa) = frequency of AA  Calculating allele frequencies from genotypes (43 individuals) 26 43 0.605 (+/+) Freq of D32 1 0.023  (0.372) 0.209 16 43 0.372 (+/D32) 2 1 43 0.023 (D32/D32) How much genetic diversity is typical?  Gel electrophoresis of many organisms shows that between 15 and 33% of all enzyme loci are polymorphic  More than one allele exists  Average individuals are heterozygous for 4–15% of loci Allelic diversity across loci  Heterozygosity or mean heterozygosity  As the average frequency of heterozygotes across loci  As the fraction of loci that are heterozygous in the genotype of the avg. individual  % of polymorphic loci  Fraction of loci in a population that have multiple alleles Heterozygosity Genetic variation at allozyme loci Why does genetic diversity persist?  Genetic diversity is much higher than traditionally thought  Selectionist theory  Natural selection favors allelic diversity  Neutral theory  Polymorphic alleles are functionally equivalent so they are not selected against  Will discuss these theories in more detail later Mutation  Mutation is a RANDOM process.  Not all conceivable mutations are equally likely to occur  Not all loci or regions within a locus are equally mutable  Environmental factors may influence the RATE of mutation (UV radiation, carcinogens, etc...) Mutation is random in two senses We can only predict the probability (likelihood) of a mutation occurring, but not which mutation will occur, or when. The chance that a particular mutation will occur is not influenced by whether or not the organism is in an environment in which that mutation would be advantageous.  Natural selection does not see, think, plan or feel, it just acts on whatever variation exists.