Genetics Mendel and the Gene Idea

Heredity What genetic principles account for the transmission of traits from parents to offspring? One possible explanation of heredity is a “blending” hypothesis - The idea that genetic material contributed by two parents mixes in a manner analogous to the way blue and yellow paints blend to make green An alternative to the blending model is the “particulate” hypothesis of inheritance: the gene idea - Parents pass on discrete heritable units, genes

Gregor Mendel Documented a particulate mechanism of inheritance through his experiments with garden peas Figure 2.2 Gregor Mendel’s monastery garden. Fig. 2.2

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. “Experiments in Plant Hybridization” Mendel was “rediscovered” in 1902 Ideas of inheritance in Mendel’s time were vague. One general idea was that traits from parents came together and blended in offspring. Thus, inherited information was predicted to change in the offspring, an idea that Mendel showed was wrong. “Characters,” or what we now call alleles, were inherited unchanged. This observation and the pattern of inheritance of these characters gave us the first definition of a gene

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

Mendel’s Experimental, Quantitative Approach Mendel used the scientific approach to identify two laws of inheritance Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned experiments Mendel chose to work with the garden pea (Pisum sativum) Because they are available in many varieties, easy to grow, easy to get large numbers Because he could strictly control which plants mated with which

Crossing Pea Plants Removed stamens from purple flower 1 5 4 3 2 Removed stamens from purple flower Transferred sperm- bearing pollen from stamens of white flower to egg- bearing carpel of purple flower Parental generation (P) Pollinated carpel matured into pod Carpel (female) Stamens (male) Planted seeds from pod Examined offspring: all purple flowers First offspring (F1)

Mendel’s experimental design Statistical analyses: Worked with large numbers of plants counted all offspring made predictions and tested them Excellent experimentalist controlled growth conditions focused on traits that were easy to score chose to track only those characters that varied in an “either-or” manner

Mendel’s Studied Discrete Traits

Genetic Vocabulary Character: a heritable feature, such as flower color Trait: a variant of a character, such as purple or white flowers 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

Antagonistic traits Dominant Recessive

Mendel’s experimental design Mendel also made sure that he started his experiments with varieties that were “true-breeding” X

Genetic Vocabulary 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) Capitalized traits = dominant phenotypes Lowercase traits= recessive phenotypes

Genetic Vocabulary 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. Dihybrid cross = cross of two different true-breeding strains (homozygotes) that differ in two traits.

Phenotype vs Genotype Figure 14.6 Phenotype Genotype Purple PP 3 1 2 Phenotype Purple White Genotype PP (homozygous) Pp (heterozygous) pp Ratio 3:1 Ratio 1:2:1

Phenotype vs Genotype Dominant & recessive alleles (Fig. 10.7):

Mendel’s Experimental Design In a typical breeding experiment Mendel mated two contrasting, true-breeding varieties, a process called hybridization The true-breeding parents are called the P generation The hybrid offspring of the P generation are called the F1 generation When F1 individuals self-pollinate the F2 generation is produced

Mendel’s Observations When Mendel crossed contrasting, true-breeding white and purple flowered pea plants all of the offspring were purple When Mendel crossed the F1 plants, many of the plants had purple flowers, but some had white flowers A ratio of about three to one, purple to white flowers, in the F2 generation EXPERIMENT True-breeding purple-flowered pea plants and white-flowered pea plants were crossed (symbolized by ). The resulting F1 hybrids were allowed to self-pollinate or were cross- pollinated with other F1 hybrids. Flower color was then observed in the F2 generation. P Generation (true-breeding parents) Purple flowers White  F1 Generation (hybrids) All plants had purple flowers F2 Generation RESULTS Both purple-flowered plants and white- flowered plants appeared in the F2 generation. In Mendel’s experiment, 705 plants had purple flowers, and 224 had white flowers, a ratio of about 3 purple : 1 white.

Mendel’s Rationale In the F1 plants, only the purple trait was affecting flower color in these hybrids Purple flower color was dominant, and white flower color was recessive Mendel developed a hypothesis to explain the 3:1 inheritance pattern that he observed among the F2 offspring There are four related concepts that are integral to this hypothesis

Heredity Concepts Alternative versions of genes account for variations in inherited characters, which are now called alleles For each character an organism inherits two alleles, one from each parent, A genetic locus is actually represented twice If the two alleles at a locus differ, the dominant allele determines the organism’s appearance The law of segregation - the two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes Allele for purple flowers Locus for flower-color gene Homologous pair of chromosomes Allele for white flowers

Law of Segregation Mechanism of gene transmission Gametogenesis: alleles segregate Fertilization: alleles unite

Mendelian Genetics Classical Punett's Square is a way to determine ways traits can segregate Parental P0 cross F1 cross Determine the genotype and phenotype

Mendelian Genetics Classical Punett's Square is a way to determine ways traits can segregate Parental P0 cross F1 cross Determine the genotype and phenotype

Mendelian Genetics Parental P0 cross F1 cross Classical Punett's Square is a way to determine ways traits can segregate Parental P0 cross F1 cross Determine the genotype and phenotype

Mendel’s Law Of Segregation, Probability And The Punnett Square Each true-breeding plant of the parental generation has identical alleles, PP or pp. Gametes (circles) each contain only one allele for the flower-color gene. In this case, every gamete produced by one parent has the same allele. P Generation  Appearance: Genetic makeup: Purple flowers PP White flowers pp Gametes: P p Union of the parental gametes produces F1 hybrids having a Pp combination. Because the purple- flower allele is dominant, all these hybrids have purple flowers. When the hybrid plants produce gametes, the two alleles segregate, half the gametes receiving the P allele and the other half the p allele. F1 Generation Appearance: Genetic makeup: Purple flowers Pp Gametes: 1/2 1/2 P p F1 sperm This box, a Punnett square, shows all possible combinations of alleles in offspring that result from an F1  F1 (Pp  Pp) cross. Each square represents an equally probable product of fertilization. For example, the bottom left box shows the genetic combination resulting from a p egg fertilized by a P sperm. P p F2 Generation P PP Pp F1 eggs p Pp pp Random combination of the gametes results in the 3:1 ratio that Mendel observed in the F2 generation. 3 : 1

Mendel’s Monohybrid Cross White (pp) Purple (Pp) Gametes Gametes p p P p Purple (PP) Purple (Pp) P P Gametes Pp Pp PP Pp Gametes p P Pp Pp Pp pp F1 generation All purple F2 generation ¾ purple, ¼ white

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

Mendel Observed The Same Pattern In Characters

The Testcross In pea plants with purple flowers the genotype is not immediately obvious A testcross Allows us to determine the genotype of an organism with the dominant phenotype, but unknown genotype Crosses an individual with the dominant phenotype with an individual that is homozygous recessive for a trait

Test Cross To determine whether an individual with a dominant phenotype is homozygous for the dominant allele or heterozygous, Mendel crossed the individual in question with an individual that had the recessive phenotype: ? Alternative 2 – Plant with dominant phenotype is heterozygous Alternative 1 – Plant with dominant phenotype is homozygous Dominant Phenotype ? PP Dominant Phenotype Pp Gametes Recessive phenotype Gametes P P P p p Recessive phenotype pp Gametes p Gametes p pp p

Test Cross To determine whether an individual with a dominant phenotype is homozygous for the dominant allele or heterozygous, Mendel crossed the individual in question with an individual that had the recessive phenotype: PP If all offspring are purple; unknown plant is homozygous. P pp p Pp Recessive phenotype Dominant Phenotype Gametes Alternative 1 – Plant with dominant phenotype is homozygous ? Pp If half of offspring are white; unknown plant is heterozygous. P p pp Recessive phenotype ? Alternative 2 – Plant with dominant phenotype is heterozygous Dominant Phenotype Gametes

then 1⁄2 offspring purple The Testcross  Dominant phenotype, unknown genotype: PP or Pp? Recessive phenotype, known genotype: pp If PP, then all offspring purple: If Pp, then 1⁄2 offspring purple and 1⁄2 offspring white: p P Pp APPLICATION An organism that exhibits a dominant trait, such as purple flowers in pea plants, can be either homozygous for the dominant allele or heterozygous. To determine the organism’s genotype, geneticists can perform a testcross. TECHNIQUE In a testcross, the individual with the unknown genotype is crossed with a homozygous individual expressing the recessive trait (white flowers in this example). By observing the phenotypes of the offspring resulting from this cross, we can deduce the genotype of the purple-flowered parent. RESULTS

The Law of Independent Assortment Mendel derived the law of segregation by following a single trait 2 alleles at a single gene locus segregate when the gametes are formed The F1 offspring produced in this cross were monohybrids, heterozygous for one character Mendel identified his second law of inheritance by following two characters at the same time Mendel was interested in determining whether alleles at 2 different gene loci segregate dependently or independently Crossing two, true-breeding parents differing in two characters produces dihybrids in the F1 generation, heterozygous for both characters

Dihybrid Cross With his monohybrid crosses, Mendel determined that the 2 alleles at a single gene locus segregate when the gametes are formed. With his dihybrid crosses, Mendel was interested in determining whether alleles at 2 different gene loci segregate dependently or independently.

Dihybrid Cross For example, in pea plants seed shape is controlled by one gene locus where round (R) is dominant to wrinkled (r) while seed color is controlled by a different gene locus where yellow (Y) is dominant to green (y). Mendel crossed 2 pure-breeding plants: one with round yellow seeds and the other with green wrinkled seeds.

Dihybrid Cross For example, in pea plants seed shape is controlled by one gene locus where round (R) is dominant to wrinkled (r) while seed color is controlled by a different gene locus where yellow (Y) is dominant to green (y). Mendel crossed 2 pure-breeding plants: one with round yellow seeds and the other with green wrinkled seeds.

Dependent Segregation If dependent segregation (assortment) occurs: Alleles at the 2 gene loci segregate together, and are transmitted as a unit. Therefore, each plant would only produce gametes with the same combinations of alleles present in the gametes inherited from its parents: R R Y Y r r y y Parents Parental Gametes R Y r y R r Y y F1 Offspring R Y r y F1 Offspring’s Gametes What is the expected phenotypic ratio for the F2?

F2 With Dependent Assortment: y R Y R Y R R Y Y R r Y y r r y y r y Ratio is 3 round, yellow : 1 wrinkled, green

Independent Segregation Alleles at the 2 gene loci segregate (separate) independently, and are NOT transmitted as a unit. Therefore, each plant would produce gametes with allele combinations that were not present in the gametes inherited from its parents: R R Y Y r r y y Parents Parental Gametes R Y r y R r Y y F1 Offspring F1 Offspring’s Gametes R Y R y r Y r y What is the expected phenotypic ratio for the F2?

Mendelian Genetics Dihybrid cross - parental generation differs in two traits example-- cross round/yellow peas with wrinkled/green ones Round/yellow is dominant What are the expected phenotype ratios in the F2 generation? round, yellow = round, green = wrinkled, yellow = wrinkled, green =

F2 with independent assortment: RY Ry rY ry RR YY Yy Rr yy rr RY Ry rY ry Phenotypic ratio is 9 : 3 : 3 : 1

Phenotypic ratio approximately 9:3:3:1 A Dihybrid Cross How are two characters transmitted from parents to offspring? As a package? Independently? A dihybrid cross Illustrates the inheritance of two characters Produces four phenotypes in the F2 generation YYRR P Generation Gametes YR yr  yyrr YyRr Hypothesis of dependent assortment independent F2 Generation (predicted offspring) 1⁄2 1 ⁄2 3 ⁄4 1 ⁄4 Sperm Eggs Phenotypic ratio 3:1 Yr yR 9 ⁄16 3 ⁄16 1 ⁄16 YYRr YyRR Yyrr YYrr yyRR yyRr Phenotypic ratio 9:3:3:1 315 108 101 32 Phenotypic ratio approximately 9:3:3:1 F1 Generation CONCLUSION The results support the hypothesis ofindependent assortment. The alleles for seed color and seed shape sort into gametes independently of each other. EXPERIMENT Two true-breeding pea plants— one with yellow-round seeds and the other with green-wrinkled seeds—were crossed, producing dihybrid F1 plants. Self-pollination of the F1 dihybrids, which are heterozygous for both characters, produced the F2 generation. The two hypotheses predict different phenotypic ratios. Note that yellow color (Y) and round shape (R) are dominant.

Dihybrid cross F2 generation ratio: 9:3:3:1

Law of Independent Assortment Mendel’s dihybrid crosses showed a 9:3:3:1 phenotypic ratio for the F2 generation. Based on these data, he proposed the Law of Independent Assortment, which states that when gametes form, each pair of hereditary factors (alleles) segregates independently of the other pairs.

Laws Of Probability Govern Mendelian Inheritance Mendel’s laws of segregation and independent assortment reflect the rules of probability The multiplication rule States that the probability that two or more independent events will occur together is the product of their individual probabilities The rule of addition States that the probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities

Laws Of Probability - Multiplication Rule The probability of two or more independent events occurring together is the product of the probabilities that each event will occur by itself Following the self-hybridization of a heterozygous purple pea plants (Pp), what is the probability that a given offspring will be homozygous for the production of white flowers (pp)? Probability that a pollen seed will carry p: ½ Probability that an egg will carry p: ½ Probability that the offspring will be pp: 1/2 X 1/2 = 1/4

Laws Of Probability - Addition Rule The probability of either of two mutually exclusive events occurring is the sum of their individual probabilities Following the self-hybridization of a heterozygous purple pea plant (Pp), what is the probability that a given offspring will be purple? Probability of maternal P uniting with paternal P: 1/4 Probability of maternal p uniting with paternal P: 1/4 Probability of maternal P uniting with paternal p: 1/4 Probability that the offspring will be purple: 1/4 + 1/4 + 1/4 = 3/4

Probability In A Monohybrid Cross Can be determined using these rules Rr Segregation of alleles into eggs   Rr Segregation of alleles into sperm Sperm 1⁄2 R 1⁄2 r R R R r 1⁄2 R 1⁄4 1⁄4 Eggs r r R r r 1⁄2 1⁄4 1⁄4

Mendel’s conclusions Genes are distinct entities that remain unchanged during crosses Each plant has two alleles of a gene Alleles segregated into gametes in equal proportions, each gamete got only one allele During gamete fusion, the number of alleles was restored to two

Summary of Mendel’s 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 (alleles). Mendel’s Law 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. Mendel’s Law of Independent Assortment: Alleles for different traits assort independently of one another. Genes on different chromosomes behave independently in gamete production.

Exceptions To Mendel’s Original Principles Incomplete dominance Codominance Multiple alleles Polygenic traits Epistasis Pleiotropy Environmental effects on gene expression Linkage Sex linkage

Incomplete dominance Neither allele is dominant and heterozygous individuals have an intermediate phenotype For example, in Japanese “Four o’clock”, plants with one red allele and one white allele have pink flowers: P Generation F1 Generation F2 Generation Red CRCR Gametes CR CW  White CWCW Pink CRCW Sperm Cw 1⁄2 Eggs CR CR CR CW CW CW

Incomplete Dominance CR CW CRCR CR CRCR CRCW CW F1 generation All CRCW Gametes CR CW CRCR CR CRCR CRCW Gametes CW F1 generation All CRCW CRCW CWCW F2 generation CWCW 1 : 2 : 1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Codominance Neither allele is dominant and both alleles are expressed in heterozygous individuals Example ABO blood types

Polygenic Traits Most traits are not controlled by a single gene locus, but by the combined interaction of many gene loci. These are called polygenic traits. Polygenic traits often show continuous variation, rather then a few discrete forms:

Epistasis Type of polygenic inheritance where the alleles at one gene locus can hide or prevent the expression of alleles at a second gene locus. Labrador retrievers one gene locus affects coat color by controlling how densely the pigment eumelanin is deposited in the fur. A dominant allele (B) produces a black coat while the recessive allele (b) produces a brown coat However, a second gene locus controls whether any eumelanin at all is deposited in the fur. Dogs that are homozygous recessive at this locus (ee) will have yellow fur no matter which alleles are at the first locus:

Epistasis E_ Dark pigment in fur ee No dark pigment in fur E_bb E_B_ eebb eeB_ Yellow fur Yellow fur Brown fur Black fur Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pleiotropy This is when a single gene locus affects more than one trait. For example, in Labrador retrievers the gene locus that controls how dark the pigment in the hair will be also affects the color of the nose, lips, and eye rims.

Environmental Effects on Gene Expression The phenotype of an organism depends not only on which genes it has (genotype), but also on the environment under which it develops. Although scientists agree that phenotype depends on a complex interaction between genotype and environment, there is a lot of debate and controversy about the relative importance of these 2 factors, particularly for complex human traits.