Mendel’s Breakthrough Patterns, Particles, and Principles of Heredity

Outline of Mendelian Genetics The historical puzzle of inheritance and how Mendel’s experimental approach helped solve it Mendel’s approach to genetic analysis including his experiments and related analytic tools A comprehensive example of Mendelian inheritance in humans

Gregor Mendel (1822-1844) Figure 2.2 Fig. 2.2

Themes of Mendel’s work Variation is widespread in nature Observable variation is essential for following genes Variation is inherited according to genetic laws and not solely by chance Mendel’s laws apply to all sexually reproducing organisms.

The historical puzzle of inheritance Artificial selection has been an important practice since before recorded history Domestication of animals Selective breeding of plants 19th century – precise techniques for controlled matings in plants and animals to produce desired traits in many of offspring Breeders could not explain why traits would sometimes disappear and then reappear in subsequent generations.

State of genetics in early 1800’s What is inherited? How is it inherited? What is the role of chance in heredity?

Mendel’s workplace Figure 2.5 Fig. 2.5

Historical theories of inheritance One parent contributes most features (e.g., homunculus, N. Hartsoiker, 1694) Blending inheritance – parental traits become mixed and forever changed in offspring Figure 2.6 Fig.2.6

Keys to Mendel’s experiments The garden pea was an ideal organism Vigorous growth Self fertilization Easy to cross fertilize Produced large number of offspring each generation Mendel analyzed traits with discrete alternative forms purple vs. white flowers yellow vs. green peas round vs. wrinkled seeds long vs. short stem length Mendel established pure breeding lines to conduct his experiments

Monohybrid crosses reveal units of inheritance and Law of Segregation Figure 2.9 Fig.2.9

Traits have dominant and recessive forms Disappearance of traits in F1 generation and reappearance in the F2 generation disproves the hypothesis that traits blend Trait must have two forms that can each breed true One form must be hidden when plants with each trait are interbred Trait that appears in F1 is dominant Trait that is hidden in F1 is recessive

Alternative forms of traits are alleles Each trait carries two copies of a unit of inheritance, one inherited from the mother and the other from the father Alternative forms of traits are called alleles

Law of Segregation Two alleles for each trait separate (segregate) during gamete formation, and then unite at random, one from each parent, at fertilization Figure 2.10 Fig. 2.10

The Punnet Square Figure 2.11 Fig. 2.11

Rules of Probability Independent events - probability of two events occurring together What is the probability that both A and B will occur? Solution = determine probability of each and multiply them together. Mutually exclusive events - probability of one or another event occurring. What is the probability of A or B occurring? Solution = determine the probability of each and add

Probability and Mendel’s Results Cross Yy xYy pea plants. Chance of Y sperm uniting with a Y egg ½ chance of sperm with Y allele ½ chance of egg with Y allele Chance of Y and Y uniting = ½ x ½ = ¼ Chance of Yy offpsring ½ chance of sperm with y allele and egg with Y allele ½ chance of sperm with Y allele and egg with y allele Chance of Yy – (½ x ½) + (½ x ½) = 2/4, or 1/2

Further crosses confirm predicted ratios Figure 2.12 Fig. 2.12

Genotypes and Phenotypes Phenotype – observable characteristic of an organism Genotype – pair of alleles present in and individual Homozygous – two alleles of trait are the same (YY or yy) Heterozygous – two alleles of trait are different (Yy)

Genotypes versus phenotpyes Yy  Yy 1:2:1 YY:Yy:yy 3:1 yellow: green Figure 2.13 Fig. 2.13

Test cross reveals unkown genotpye Figure 2.14 Fig. 2.14

Dihybrid crosses reveal the law of independent assortment A dihybrid is an individual that is heterozygous at two genes Mendel designed experiments to determine if two genes segregate independently of one another in dihybrids First constructed true breeding lines for both traits, crossed them to produce dihybrid offspring, and examined the F2 for parental or recombinant types (new combinations not present in the parents)

Results of Mendels dihybrid crosses F2 generation contained both parental types and recombinant types Alleles of genes assort independently, and can thus appear in any combination in the offspring

Dihybrid cross shows parental and recombinant types Figure 2.15 top Fig. 2.15 top

Dihybrid cross produces a predictable ratio of phenotypes Figure 2.15 bottom Fig. 2.15 bottom

The law of independent assortment During gamete formation different pairs of alleles segregate independently of each other Figure 2.16 Fig. 2.16

Summary of Mendel's work Inheritance is particulate - not blending There are two copies of each trait in a germ cell Gametes contain one copy of the trait Alleles (different forms of the trait) segregate randomly Alleles are dominant or recessive - thus the difference between genotype and phenotype Different traits assort independently

Laws of probability for multiple genes P RRYYTTSS X rryyttss F1 RrYyTtSs X RrYyTtSs F2 What is the ratio of different genotypes and phenotypes? gametes RYTS ryts RyTS rYTS RYTs RyTs rYTs RYtS RytS rYts Ryts RYts ryTs rYtS

Punnet Square method - 24 = 16 possible gamete combinations for each parent Thus, a 16  16 Punnet Square with 256 genotypes That’s one big Punnet Square! Loci Assort Independently - So we can look at each locus independently to get the answer.

What is the probability of obtaining the genotype RrYyTtss? F1 RrYyTtSs  RrYyTtSs What is the probability of obtaining the genotype RrYyTtss? P RRYYTTSS  rryyttss Rr  Rr 1RR:2Rr:1rr 2/4 Rr Yy X Yy 1YY:2Yy:1yy 2/4 Yy Tt  Tt 1TT:2Tt:1tt 2/4 Tt Ss  Ss 1SS:2Ss:1ss 1/4 ss Probability of obtaining individual with Rr and Yy and Tt and ss. 2/4  2/4  2/4  1/4 = 8/256 (or 1/32)

F1 RrYyTtSs  RrYyTtSs P RRYYTTSS  rryyttss What is the probability of obtaining a completely homozygous genotype? Genotype could be RRYYTTSS or rryyttss Rr  Rr 1RR:2Rr:1rr 1/4 RR 1/4 rr Yy  Yy 1YY:2Yy:1yy 1/4 YY 1/4 yy Tt  Tt 1TT:2Tt:1tt 1/4 TT 1/4 tt Ss  Ss 1SS:2Ss:1ss 1/4 SS 1/4 ss (1/4  1/4  1/4  1/4) + (1/4  1/4  1/4  1/4) = 2/256

Rediscovery of Mendel Mendel’s work was unappreciated and remained dormant for 34 years Even Darwin’s theories were viewed with skepticism in the late 1800’s because he could not explain the mode of inheritance of variation In 1900, 16 years after Mendel died, four scientists rediscovered and acknowledged Mendel’s work, giving birth to the science of genetics

1900 - Carl Correns, Hugo deVries, and Erich von Tschermak rediscover and confirm Mendel’s laws Figure 2.19 Fig. 2.19

Mendelian inheritance in humans Most traits in humans are due to the interaction of multiple genes and do not show a simple Mendelian pattern of inheritance. A few traits represent single-genes. Examples include sickle-cell anemia, cystic fibrosis, Tay-Sachs disease, and Huntington’s disease (see Table 2.1 in text) Because we can not do breeding experiments on humans, we use model organisms.

In humans we must use pedigrees to study inheritance Pedigrees are an orderly diagram of a families relevant genetic features extending through multiple generations Pedigrees help us infer if a trait is from a single gene and if the trait is dominant or recessive

Anatomy of a pedigree Figure 2.20 right Fig. 2.20

A vertical pattern of inheritance indicates a rare dominant trait Figure 2.20 left Fig. 2.20 Hunitington’s disease: A rare dominant trait Assign the genotypes by working backward through the pedigree

A horizontal pattern of inheritance indicates a rare recessive trait Figure 2.21 Fig.2.21 Cystic fibrosis: a recessive condition Assign the genotypes for each pedigree