Population Genetics Notes

NOTES NOTES POPULATION GENETICS MENDELIAN GENETICS & PUNNETT SQUARES osms.it/mendelian-genetics-punnett-squares ▪ Genetics: science of inheritance ▪ Parental generation (“P”) → 1st filial generation (“F1”) → 2nd filial generation (“F2”) ▪ Homozygous: male, female alleles are same ▪ Heterozygous: male, female alleles differ ▪ Phenotype: observable trait from genotype Mendel’s laws ▪ Law of segregation: alleles segregate, offspring acquire one allele from each parent ▪ Law of dominance: alleles can be dominant/recessive ▫ Dominant traits appear when ≥ one dominant allele is present ▪ Law of independent assortment: separate genes assort independently ▫ Genetic linkage: proximity of genes on chromosome can cause joint assortment Punnett square ▪ Table showing possible combinations of genotypes Figure 41.1 2x2 Punnett squares showing the allele combinations for one gene: flower color in pea plants. The parent plants are homozygous for the flower color trait. When they are crossbred (first Punnett square), each offspring in the F1 generation gets one dominant allele (P) and one recessive allele (p). The dominant P allele masks the recessive p allele, so all the flowers appear violet. When any two of the heterozygous F1 generation plants are bred (second Punnett square), the three plants in the F2 generation with at least one P allele have a violet flower phenotype and the one plant with the homozygous pp genotype has a white flower phenotype. 338 OSMOSIS.ORG

Chapter 41 Genetics: Population Genetics Figure 41.2 4x4 Punnett square showing the allele combinations for two genes: seed color (Y = yellow, y = green) and texture (R = round, r = wrinkly). One parent (P) plant is homozygous dominant (YYRR; yellow, round seeds), the second is homozygous recessive (yyrr; green, wrinkled seeds). When these plants are crossbred, all the F1 generation plants have the genotype YyRr and the phenotype of yellow, round seeds. When the F1 generation plants are bred (Punnett square), there are four possible combinations of the alleles for each parent: YR, Yr, yR, and yr. We can expect the F2 generation to have four phenotypes: yellow and round (≥ one Y and ≥ one R), yellow and wrinkled (≥ one Y and two r), green and round (two y and ≥ one R), green and wrinkled (yyrr). They appear in the ratio 9:3:3:1. INDEPENDENT ASSORTMENT OF GENES & LINKAGE osms.it/independent-assortment-and-linkage ▪ Independent assortment: separate genes assort independently ▫ Apart from in genetic linkage ▫ Genetic linkage: proximity of genes on chromosome can cause joint assortment ▪ Crossing-over: in prophase 1 of meiosis, genes can be exchanged between adjacent chromosomes ▫ Homozygous genes can occur on different gametes ▫ Even repetitions of crossing-over can reverse this effect ▪ Linked genes have < 50% chance of occurring on different gametes ▫ Parental gametes: linked genes inherited together ▫ Recombinant gametes: linked genes between which crossing-over has occurred OSMOSIS.ORG 339

Figure 41.3 Red chromosome from female parent originally carried all dominant alleles for genes A, B, C; blue chromosome from male parent originally carried all recessive alleles for genes A, B, C. If crossing over occurs between the ends of the two chromosomes, dominant allele C from female parent ends up in the chromosome from male parent, vice versa. Figure 41.4 Any two genes on different chromosomes always have a 50% chance of going through crossing over in meiosis and showing up in the same gamete. The same is true for two genes very far apart on the same chromosome, because ending up in the same or a different gamete depends on whether there are an odd or even number of crossing over events. 340 OSMOSIS.ORG

Chapter 41 Genetics: Population Genetics Figure 41.5 It is unlikely for a cut to occur in the small space between linked genes, which is why the chance of them crossing over and ending up in different gametes is < 50%. When linked genes are inherited together, the gametes are called “parental” because they carry same the alleles as the original chromosomes. When crossing over occurs, they are called “recombinant.” INHERITANCE PATTERNS osms.it/inheritance-patterns Dominant vs. recessive inheritance patterns ▪ Dominant inheritance: mutation affects dominant allele → one copy causes disease ▪ Recessive inheritance: mutation affects recessive allele → two copies cause disease Autosomal vs. sexual vs. mitochondrial patterns ▪ Autosomal inheritance: mutation affects somatic chromosome ▪ Sexual inheritance: mutation affects sex chromosome; X-linked/Y-linked ▪ Mitochondrial inheritance: mutation on egg’s mitochondrial DNA Autosomal inheritance ▪ Autosomal dominant inheritance (e.g. Huntington’s disease) ▫ Dominant homozygotes (RR), heterozygotes (Rr) have disease ▫ Recessive homozygotes (rr) unaffected ▫ Disease too severe in homozygotes → don’t reproduce OSMOSIS.ORG 341

Figure 41.6 Autosomal dominant inheritance. Punnett square demonstrating probabilities of healthy and disease genotypes in offspring when a heterozygous dominant individual (Dd) reproduces with a healthy individual (dd). ▪ Autosomal recessive inheritance (e.g. cystic fibrosis) ▫ Only recessive homozygotes have disease ▫ Heterozygotes carriers ▫ Tendency to skip generation ▫ Children of consanguineous unions: ↑ likelihood of disease Figure 41.7 Autosomal recessive inheritance. Punnett square demonstrating probabilities of healthy, disease, and carrier genotypes in the offspring when two healthy carriers reproduce. 342 OSMOSIS.ORG Figure 41.8 Autosomal recessive inheritance. When one affected and one unaffected individual reproduce, all offspring are carriers. Sex-linked inheritance ▪ Males have one allele for genes on X, Y chromosomes (hemizygous) ▪ Females have two alleles for genes on X chromosomes (homozygous/heterozygous) ▪ X-linked dominant inheritance (e.g. fragile X syndrome) ▫ Dominant hemizygotes, dominant homozygotes, heterozygotes have disease ▫ Males reproducing with healthy females have 100% chance to pass onto female children, 0% chance to pass onto male children ▫ Females reproducing with healthy males have 50% chance to pass onto children of both sexes ▪ X-linked recessive inheritance (e.g. hemophilia) ▫ Recessive homozygotes, recessive hemizygotes have disease; heterozygotes are carriers ▫ Males reproducing with healthy females have 100% chance of female children being carriers, 0% chance of passing disease onto male children ▫ Heterozygous females reproducing with healthy males have 50% chance of female children being carriers, 50% chance of passing disease onto male children ▪ Y-linked inheritance (e.g. baldness) ▪ Only male heterozygotes have disease

Chapter 41 Genetics: Population Genetics ▪ Always passed from biologically-male parent to biologically-male child Mitochondrial inheritance ▪ Mitochondrial inheritance (e.g. DAD, AKA diabetes mellitus and deafness) ▫ Males, females can develop disease ▫ Only females can pass disease to offspring Figure 41.9 Punnett squares demonstrating the inheritance patterns for fragile X syndrome, an X-linked dominant disease, with different combinations of parental genotypes. Figure 41.10 Punnett squares demonstrating the inheritance patterns for hemophilia, an X-linked recessive disease, with different combinations of parental genotypes. OSMOSIS.ORG 343

EVOLUTION & NATURAL SELECTION osms.it/evolution-natural-selection Evolution ▪ Process by which populations change over time ▫ Population: group of organisms within species that live in same place ▫ Species: group of organisms with similar characteristics, ability to breed Natural selection ▪ Premises ▫ Individuals in species have different traits ▫ Some individuals survive, reproduce ▫ Some traits → ↑ survival, reproduction (AKA fitness) ▫ → more offspring with these traits (AKA differential reproduction) ▪ Conclusion ▫ Population slowly changes over time to favor useful traits (e.g. ↑ survival, reproduction) ▪ Artificial selection = selective breeding HARDY—WEINBERG EQUILIBRIUM osms.it/hardy-weinberg_equilibrium ▪ Population’s genetic traits remain same from one generation to next in absence of evolutionary changes (e.g. natural selection, mutation, genetic drift) ▫ Natural selection causes population to favor useful traits ▫ Mutation causes new traits to arise ▫ Genetic drift causes trait prominence to shift by chance (AKA sampling error) 344 OSMOSIS.ORG ▪ Given probability p of dominant allele A, probability q of recessive allele a ▫p+q=1 ▫ prob(AA) = p2 ▫ prob(aa) = q2 ▫ prob(Aa) = 2pq ▪ q can be calculated from phenotype ▫ Square root of frequency of recessive phenotype ▫ → frequency of other phenotypes can be calculated

Chapter 41 Genetics: Population Genetics EPIGENETICS osms.it/epigenetics ▪ Mechanisms to selectively activate/silence genes without modifying nucleotide sequence Histone modification ▪ Acetylation ▫ Removes positive charge → less attraction to negative DNA phosphates → ↑ gene transcription ▪ Methylation ▫ One methyl group → loosens histone tails → ↑ access for transcription factors → ↑ gene transcription ▪ ▪ ▪ ▪ ▫ 2-3 methyl groups → tightens histone tails → ↓ access for transcription factors → ↓ gene transcription Direct DNA modification ▫ Usually occurs in long sequences of cytosine,guanine nucleotides (AKA CpG) ▫ Cytosine residues undergo methylation, silencing gene expression Modifications occur throughout lifetime Affected by environmental factors (e.g. drug usage, diet, exercise) Changes are reversible LAC OPERON osms.it/lac-operon ▪ Collection of genes in E. coli, other bacteria that code for proteins required to transport, metabolize lactose ▪ Includes structural genes like lacZ, lacY, lacA as well as regulatory genes like promoter, operator ▫ lacZ: β-galactosidase (AKA lactase) ▫ lacY: β-galactosidase permease ▫ lacA: β-galactosidase transacetylase ▫ Promoter: start transcription ▫ Operator: prevent transcription with repressor (coded by lacI) ▪ Glucose, lactose concentrations can be used to regulate lac operon expression ▫ ↑ glucose → repressor stays bound to operator, blocking RNA polymerase ▫ ↑ glucose → catabolite activator protein inhibits transcription ▫ ↓ glucose → repressor falls off ▫ ↓ glucose → catabolite activator protein stimulates transcription Figure 41.11 The lac operon. β-galactosidase breaks down lactose into glucose and galactose; β-galactosidase permease allows lactose to enter the cell; β-galactosidase transacetylase’s function is not clearly understood. OSMOSIS.ORG 345

GENE REGULATION osms.it/gene-regulation ▪ Natural regulation of gene expression ▪ Occurs at transcription/post-transcription/ translation level ▪ Transcriptional regulation ▫ Epigenetics: chemical modifications activate/silence genes without modifying nucleotide sequence (e.g. by methylation/acetylation of histones) ▫ Activators: bind to DNA enhancer → facilitate binding of general transcription factors, recruit histone acetyltransferases ▫ Repressors: bind to DNA silencer → prevent RNA polymerase from binding to promoter, recruit histone deacetylases ▪ Post-transcriptional regulation ▫ Splicing: spliceosomes remove introns (AKA non-coding sequences) from RNA → resulting mRNA codes for proteins more effectively ▫ Capping: 5’ end of RNA capped with protective 7-methyl-guanine → exonucleases unable to cleave off nucleotides ▫ Editing: proteins convert certain nucleotides (e.g. ADAR: adenosine → inosine; CDAR: cytosine → uracil) to create sequence variation ▪ Translation regulation ▫ Mainly occurs during initiation ▫ Regulatory proteins (AKA initiation) factors must bind before ribosome can begin translation ▫ Conditions like starvation, stress inhibit initiation factors to save energy Figure 41.12 An activator looping DNA in the nucleus. Figure 41.14 Illustration depicting the action of spliceosomes. Figure 41.13 A repressor protein in the nucleus binding the DNA sequence called the silencer, which is on the same DNA strand as the gene. 346 OSMOSIS.ORG

Chapter 41 Genetics: Population Genetics GEL ELECTROPHORESIS & GENETIC TESTING osms.it/gel-electrophoresis-genetic-testing ▪ Method of separating, analyzing macromolecules (e.g. DNA, RNA, proteins), their fragments based on size, charge Apparatus ▪ Clear box filled with gel, often agarose ▫ Small depressions (AKA “wells”) at one end ▫ Sample macromolecules placed separately in wells ▪ Power source connected to gel Premise ▪ Current applied → macromolecule fragments move through gel ▪ Charge of fragments determines ▫ Direction: opposites attract ▫ Speed: greater magnitude → faster ▪ Fragment size also determines speed ▫ Gel contains small pores; smaller size → faster ▪ Fast-moving fragments travel further over given period → production of multiple bands (one per fragment) Applications ▪ DNA analysis (e.g. genetic fingerprinting) ▫ DNA chopped up with restriction enzymes (e.g. EcoRI cuts at GAATTC) ▫ Fragments poured into wells, current applied ▫ Fragments move towards positive terminal, form bands at isoelectric point ▪ Identifying DNA mutations ▫ Mutation → restriction enzymes create different fragments → bands change ▫ Smaller fragments → bands are further apart ▫ More abundant fragments → bands (thicker, brighter) ▪ Other applications: estimation of molecule size, macromolecule separation Figure 41.15 Identifying DNA mutations using EcoRI. A mutation in a single nucleotide from A to G in the EcoRI binding site prevents the enzyme from binding and cutting at that location. Now, in gel electrophoresis, there will be only three lines (instead of four) and one fragment will be longer, indicating that the DNA contains a mutation. OSMOSIS.ORG 347

POLYMERASE CHAIN REACTION osms.it/polymerase-chain-reaction ▪ Technique used to amplify desired DNA segment ▪ Based on DNA melting, enzyme-driven DNA replication ▪ Takes place in thermal cycler ▪ Four essential components ▫ Template DNA: strand to be replicated ▫ Nucleotides: building blocks of DNA ▫ Primers: short complementary DNA strands to the 3’ end of each strand ▫ DNA polymerase: enzyme that synthesizes DNA from nucleotides (e.g. Taq polymerase) 348 OSMOSIS.ORG Process ▪ Denaturation: sample heated to 96°C/205°F → bonds between DNA strands separate, forming two template strands ▪ Annealing: sample cooled to 55°C/131°F → primers bind to template strands ▪ Extension: sample heated to 72°C/162°F → Taq polymerase synthesizes complete complementary DNA strands, starting from end of each primer Applications ▪ Cloning DNA into plasmids, replicating DNA for analysis (e.g. research and practice)