Classical Genetics Lectures: Chapter 11 Mendelian Genetics Chapter 12 Chromosomal inheritance, sex linkage & determination Chapter 13 Extensions of Mendelian Genetics (multiple alleles, gene interactions, etc.) Non-Mendelian Inheritance (mtDNA, chloroplasts, maternal effects, etc.) Epigenetic Inheritance

Numerous factors contribute to the phenotype: Genotype Activities of genes & gene products Environment & development Phenotype Genotype = collection of genes (and alleles) in an organism Phenotype = observable properties of an organism

Is inheritance blending or particulate? In the mid 19th century,biologists believed that inheritance was blending, that is, traits of offspring were the average of their parents. Problematic because new genetic variations would quickly be diluted and could not be accumulated and passed to subsequent generations as theory of evolution predicted. Blending inheritance was quickly discredited by Gregor Mendel’s experiments, which showed that inheritance is particulate. F1 F2

Mendelian Genetics: Gregor Johann Mendel (1822-1884) Augustinian monk, Czech Republic. Foundation of modern genetics. Studied segregation of traits in the garden pea (Pisum sativum) beginning in 1854. Published his theory of inheritance in 1865. “Versuche über Pflanzen-Hybriden” “Experiments in Plant Hybridization” Mendel was “rediscovered” in 1902.

Mendel’s Experiments: Began by self-fertilizing 34 different pea strains (phenotypes) so that they bred true (selfing, the opposite of cross-fertilization). Focused on 7 well-defined garden pea traits by crossing different phenotypes one at a time: Flower/seed coat color: purple vs. white flowers grey vs. white seed coats (*controlled by single gene) Seed color: yellow vs. green Seed shape: smooth vs. wrinkled Pod color: green vs. yellow Pod shape: inflated vs. pinched Stem height: tall vs. short Flower position: axial vs. terminal Counted offspring of each phenotype and analyzed the results mathematically.

Fig. 11.4, Mendel’s 7 garden pea characters.

Some basic terminology: Generations: P = parental generation F1 = 1st filial generation, progeny of the P generation F2 = 2nd filial generation, progeny of the F1 generation (F3 and so on) Crosses: Monohybrid cross = cross of two different true-breeding strains (homozygotes) that differ in a single trait. Reciprocal cross = sexes for the two strains are reversed (and if the results are the same, trait is not sex-linked). Dihybrid cross = cross of two different true-breeding strains (homozygotes) that differ in two traits. *Genetics etiquette - female conventionally is written first

Dominant & recessive alleles (Fig. 11.7):

Results of Mendel’s monohybrid parental cross: “Mendel’s Principle of Uniformity in F1” F1 offspring of a monohybrid cross of true-breeding strains resemble only one of the parents. Why? Smooth seeds (allele S) are completely dominant to wrinkled seeds (allele s). Fig. 11.5

Fig. 11.8 Smooth and wrinkled parental seed strains crossed. Punnett square F1 genotypes 4/4 Ss F1 phenotypes 4/4 smooth

F1 x F1 crosses (Fig. 11.6): Mendel also discovered that traits that disappear in the F1 generation reappear in the F2 generation in a 1:3 ratio. “Mendel’s Principle of Segregation”

F1 x F1 Punnett square (Fig. 11.8): F2 genotypes 1/4 SS 1/2 Ss 1/4 ss F2 phenotypes 3/4 smooth 1/4 wrinkled

Fig. 11.9, Crosses also can be represented with branching diagrams.

What about the six other phenotypic traits? Results of reciprocal crosses always were the same. F1 progeny always resemble the parental strain. In the F2 progeny, parental strain lost in the F1 generation always reappeared at a ratio of 1:3. “Mendel’s Principle of Segregation”: Recessive characters masked in the F1 progeny of two true-breeding strains, reappear in a specific proportion of the F2 progeny. Modern formulation of Mendel’s Principle of Segregation: Two members of a gene pair segregate (separate) from each other during the formation of gametes.

Confirming the Principle of Segregation with test-crosses: SS x SS  true breeding (100% homozygous dominant) ss x ss  true breeding (100% homozygous recessive) How do you determine whether an individual with the dominant phenotype is homozygous or heterozygous? Cross it with homozygous recessive: SS x ss  4/4 dominant trait Ss x ss  1/2 dominant trait + 1/2 recessive trait

Fig. 11.11, Test Crosses

Mendel’s dihybrid crosses: Mendel also performed crosses involving two pairs of traits, e.g., seed shape (smooth vs. wrinkled) and color (yellow vs. green). If alleles sort independently, four possible phenotypes (2n) appear in the F2 generation in a 9:3:3:1 ratio. “Mendel’s Principle of Independent Assortment”: Alleles for different traits assort independently of one another. Modern formulation of independent assortment: Genes on different chromosomes behave independently in gamete production.

Fig. 11.12a Dihybrid cross: F1 generation

Fig. 11.12b Dihybrid cross: F2 generation Ratio: 9:3:3:1

Trihybrid crosses: Involve three independently assorting character pairs. Results: 64 combinations of 8 different gametes 27 different genotypes 8 different phenotypes (2 x 2 x 2) Predicted ratio of phenotypes = 27:9:9:9:3:3:31

Summary of Mendel’s Three Principles: Mendel’s Principle of Uniformity in F1: F1 offspring of a monohybrid cross of true-breeding strains resemble only one of the parents. Why? Smooth seeds (allele S) are completely dominant to wrinkled seeds (allele s). Mendel’s Principle of Segregation: Recessive characters masked in the F1 progeny of two true-breeding strains, reappear in a specific proportion of the F2 progeny. Two members of a gene pair segregate (separate) from each other during the formation of gametes. Inheritance is particulate, not blending as previously believed. Mendel’s Principle of Independent Assortment: Alleles for different traits assort independently of one another. Genes on different chromosomes behave independently in gamete production.

Rediscovery of Mendel’s Principles: William Bateson (1902)-experiments with fowl first demonstrated that Mendel’s principles applied to animals. Bateson argued that mutation (not selection) was the most important force shaping variation in plants and animals. William Bateson also coined the terms: Genetics Zygote F1 F2 Allelemorph ( allele) 1907 - Reginald Punnett and William Bateson

Founded The Genetics Society in 1919 1905 - Letter from Bateson to Alan Sedgewick Founded The Genetics Society in 1919

Statistical analysis of genetic data: Mendelian ratios can be predicted mathematically  null hypothesis. Null hypothesis = difference is due to chance. Compare null hypothesis to observed data with goodness of fit test. Chi-square (2) test is one of the most common GF tests, developed by Karl Pearson. 2 =  (# observed - # expected)2 / # expected Requires a P-value (probability that the difference between observed and expected values is due to chance). P-value is obtained from a table of probability values (0.05, 0.10. 0.30, etc.) and known degrees of freedom (df). P = 0.05 is typical cited as significant. df = # phenotypic classes - 1 (n - 1)

Test-cross: SsYy x ss yy  1/4 + 1/4 + 1/4 + 1/4 (see Table 10.2) Phenotype # obs. # exp. obs - exp (O - E)2 (O - E)2/E Smooth/ yellow 136 142 -6 36 0.25 Smooth/ green 138 -4 16 0.11 Wrinkled/ yellow 144 +2 4 0.03 Wrinkled/ green 146 +4 df = 4 -1 =3, Critical 2 for P = 0.05 and 3 df = 7.82 0.50

G-test: Alternative to Chi-Square test Likelihood ratio test of statistical significance where Oi = observed counts and Ei = expected counts G is approximated by Chi-square, but G provides a better approximation to the chi-sq distribution than the Chi-square test.