Genetics and Evolution Welcome to IB 201! Genetics and Evolution

IB 201: Review Question A phenotype ratio of 9:3:3:1 in the offspring of a mating between two individuals that are heterozygous for two traits occurs when: A. the genes reside on the same chromosome B. each gene contains two mutations C. the gene pairs assort independently during meiosis D. only recessive traits are scored E. none of the above

Course Outline Genetic Data Analysis: Probability & Statistics Deviations from Mendelism: Epistasis; Unusual Modes of Inheritance Chromosomal Inheritance: Chromosomal Abnormalities; Sex Determination Mapping: Gene and Genome Mapping Traits Affected by Genes & Environment Quantitative Traits Genes in Populations Genetic Mechanisms of Evolution; Population Genetics of Disease and Disease resistance

Genetic Data Analysis II Some simple rules of probability

Sum Rule The combined probability of two events that are mutually exclusive is the sum of the individual probabilities. Clue: look for “or” Q: What’s the probability of rolling a ‘five’ or a ‘six’ on one six-sided die? A: 1/6 + 1/6 = 1/3

Genetic Example: Monohybrid Cross P: GG x gg F1: Gg Gg x Gg ==> F2: 1/4 GG: 1/2 Gg: 1/4 gg What is the probability that the F2 offspring has the dominant phenotype (is either GG or Gg)? 1/4 GG + 1/2 Gg = 3/4 G-

Genetic Example 2: Dihybrid Cross P: GG ww x gg WW F1: Gg Ww Gg Ww x Gg Ww ==> F2: 9/16 G-W- 3/16 G-ww 3/16 ggW- 1/16 ggww What is the probability that an F2 offspring will have the dominant phenotype (G-ww or ggW-) for only one of the two traits? 3/16 G-ww + 3/16 ggW- = 6/16=3/8

Product Rule The probability of several independent events is the product of the individual probabilities. Two events are independent if the occurrence of the first event has no effect on the probability of the second event. Clue: look for “and”. Q: You roll two dice. What’s the probability of getting a ‘two’ on the first one and a ‘five’ on the second one. A: 1/6 * 1/6 = 1/36

Genetic example of product rule P: AA bb CC DD ee ff x aa BB cc dd EE FF F1: Aa Bb Cc Dd Ee Ff x Aa Bb Cc Dd Ee Ff Q: What proportion of F2 progeny will be AA bb Cc DD ee Ff ? A: 1/4 * 1/4 * 1/2 * 1/4 * 1/4 * 1/2 = 1/1024

Deviations from Mendelism Lethal Alleles Epistasis Unusual sex linkage Sex influenced inheritance Genetic Anticipation

Manx Cats

Lethal alleles F1: Mm x Mm F1: 1 MM 2 Mm 1 mm F2: 1 Lethal: 2 Manx: 1 Normal F2 phenotypic ratio: 2:1 instead of 3:1

Other lethal mutations Achondroplasia (humans) Yellow body color (domestic mice) Curly wings (Drosophila)

Epistasis Genetic interaction between two (or more) loci. One gene modifies the phenotypic effects of another gene.

Agouti: wild type Figure: 04-00CO Caption: Agouti, yellow, and black mice.

F2: 9/16 B- C- 3/16 bb C- 3/16 B- cc 1/16 bb cc agouti black albino BB CC x bb cc P: agouti albino Bb Cc F1: agouti Simple dominant phenotype? F2: 9/16 B- C- 3/16 bb C- 3/16 B- cc 1/16 bb cc agouti black albino albino F2 Phen. ratio: 9 agouti : 3 black : 4 albino novel phenotype

Epistasis Normal dihybrid ratio is altered from 9:3:3:1 to 9:3:4 C and B gene have an epistatic interaction

Epistasis Locus 1 Locus 2 BB Bb bb CC Cc cc agouti agouti black no effect no effect albino

Biochemical model CC or Cc: tyrosinase is produced (involved in production of melanin) BB or Bb: controls distribution of the pigment

rrYY RRyy Codominance? R-Y- R-Y- rrY- R-yy rryy Figure 10.18b Crosses between pure lines produce novel colors. Parental generation rrYY RRyy X Yellow Brown Codominance? F1 generation R-Y- Red Self-fertilization Figure: 10.18b Caption: Inheritance of Fruit Color in Bell Peppers F2 generation R-Y- rrY- R-yy rryy Red Yellow Brown Green 9/16 3/16 3/16 1/16

yellow ----------------> green -----------------> brown pepper Figure 10.18c Model to explain 9 : 3 : 3 : 1 pattern observed above: Two genes interact to produce pepper color. yellow ----------------> green -----------------> brown pepper yy? chlorophyll R? red pigment yellow -------------------> yellow ------------------> orange Y? No chlorophyll R? red pigment Genotype Color Explanation of color R-Y- Red Red pigment + no chlorophyll rrY- Yellow Yellow pigment + no chlorophyll R-yy Brown Red pigment + chlorophyll rryy Green Yellow pigment + chlorophyll Gene 1 Figure: 10.18c Caption: Inheritance of Fruit Color in Bell Peppers Gene 2 R = Red Y = Absence of green (no chlorophyll) r = Yellow y = Presence of green (+ chlorophyll) (-) = R or r (-) = Y or y

Practice Problem In Labrador retrievers, coat color is controlled by two loci each with two alleles B,b and E,e respectively. When pure breeding Black labs with genotype BB EE are crossed with pure breeding yellow labs of genotype bb ee the resulting F1 offspring are black. F1 offspring are crossed (Bb Ee x Bb Ee). Puppies appear in the ratio: 9/16 black; 3/16 chocolate; 4/16=1/4 yellow. What genotypes correspond to these three phenotypes? 9/16 B- E- 3/16 B- ee 3/16 bb E- 1/16 eebb B- E- B- ee bb E- and bb ee

Other kinds of epistasis 9/16 A-B- 3/16 A-bb 3/16 aaB- 1/16 aabb Figure: 04-07 Caption: Basis of modified dihybrid F2 phenotypic ratios. Hint: usually given numbers, not fractions 27 agouti; 12 albino; 9 black 28 agouti; 11 albino; 4 black

Practice Problem In the summer squash (Cucurbita pepo) fruit shape is determined by two genes. Two different true-breeding spherical types were crossed. The F1's were all disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results. What’s the first step? Notice novel phenotype: disk, long. What’s the next step? Notice there are three F2 phenotypes. What kind of inheritance will give three F2 phenotypes? Genetic Model? Incomplete, codominance Epistasis Expected F2 ratio? 1:2:1 Variation on 9:3:3:1

Practice Problem, cont. In the summer squash (Cucurbita pepo) spherical fruit is recessive to disk, True-breeding spherical types from different geographic regions were crossed. The F1's were disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results. Are the phenotypic ratios closer 1:2:1 or to a variant of 9:3:3:1 ? If phenotypic ratios closer to a variant of 9:3:3:1, then what variant is it? Total # of individuals = 35 + 25 + 4 = 64 64/16 = 4 9*4 = 36 6*4 = 24 1*4 = 4 Phenotypic ratio close to 9:6:1

Practice Problem, cont. AA bb aaBB In the summer squash (Cucurbita pepo) spherical fruit is recessive to disk, True-breeding spherical types from different geographic regions were crossed. The F1's were disk, and the F2's segregated 35 disk, 25 spherical and 4 long. Explain these results. If phenotypic ratios are close to 9:6:1, then what are the genotypes associated with each phenotype? 35 disk 25 spherical 4 long 9/16 A- B- 3/16 A- bb + 3/16 aa B- 1/16 aa bb What were the genotypes of the original spherical parents? AA bb aaBB

Sex Linkage: mammals, flies Heterogametic Sex Diploid XAXa XAY Adults Gametes XA Xa XA Y XA Y Male XA XAXA XAY Female Xa XAXa XaY

Sex Linkage: birds, butterflies Homogametic Sex Heterogametic Sex Diploid ZBW ZBZb Adults Female Male Gametes ZB W ZB Zb ZB Zb Male ZB ZBZb ZBZb Female W ZBW ZbW

Y-linked inheritance

Hairy ears

Male pattern baldness: what kind of inheritance?

Sex influenced phenotype Genotype Female Male bb Bald Bald bb’ Not bald Bald b’b’ Not bald Not bald

Environment-dependent dependent expression of a genotype

Siamese or “Himalayan” Different allele of the C locus that causes albinism. Temperature sensitive.

Phenotypes are not always a direct reflection of genotypes Temperature-sensitive alleles: Siamese color pattern Nutritional effects: phenylketonuria Genetic anticipation: several genetic diseases

Phenylketonuria Nutritional defect: can’t metabolize phenylalanine. Can lead to severe physical and mental disorders in children, but only if they consume phenylalanine. Disease phenotype can be avoided by eliminating phenylalanine from the diet

Genetic Anticipation Huntington disease Fragile-X syndrome Kennedy disease Myotonic muscular dystrophy

Fragile X syndrome Symptoms: delayed development & mental retardation. More severe in males than females Caused by expansion of triplet repeat (CGG) in a gene on the long arm of the X chromosome Named for breakage of X chromosome in cell preparations.

Fragile X Normal range: 7-52 (average=30) “Pre-mutation”: 60-200 repeats Full Mutation: > 230-1000s. DNA becomes abnormally methylated, promoter is inactivated, and gene silenced. Pre-mutation is unstable: maternally-inherited premutation with >100 repeats almost always expands to a full mutation

Genetic Anticipation: Fragile X Most common kind of inherited mental retardation. Named for “fragile site” Due to expansion of 3-base pair repeat (CGG) in a gene near the tip of the long arm of X chromosome.

Fragile X Pre-mutation is unstable: maternally-inherited premutation with >100 repeats almost always expands to a full mutation

Genetic Anticipation causes subsequent generations in a family to be more severely affected by a disease. It does this by increasing the number of triplet repeats in the fragile area of the X chromosome through the generations.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Huntington Disease Autosomal dominant lethal (chromosome 4) Progressive neurological deterioration First symptoms appear after reproductive age One of 8 known neurodegenerative diseases caused by expansion of (CAG) repeats All show inverse correlation with age of onset and number of repeats.

Which is the pedigree of autosomal dominant (like HD)