Mendel and the Gene Idea

1. Chapter 14 Mendel and the Gene Idea

2. Genetic Principles • What genetic principles account for the passing of traits from parents to offspring? • the “blending” hypothesis genetic material from the two parents blends together • like blue and yellow paint blend to make green • over enough generations – you will get a uniform population • the “particulate” hypothesis parents pass on discrete heritable units (genes) • this hypothesis can explain the reappearance of traits after “skipping” several generations

3. 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 • region now part of the Czech Republic • Olmutz Philosophical Institute • entered an Augustine monastery in 1843 – 21 yrs old • one of his mentors – Christian Doppler (proponent of the scientific method)

4. Mendel’s Experimental, Quantitative Approach • Advantages of pea plants for genetic study • there are many varieties with distinct heritable features, or characters - such as flower color • character variations (such as purple or white flowers) are called traits • mating can be controlled through the control of pollination • each flower has sperm-producing organs (stamens) and an egg-producing organ (carpel) • could remove the reproductive parts of one plant before meiosis • cross-pollination involved dusting one plant with pollen from another

5. Mendel chose to track only those characters that occurred in two distinct alternative forms • e.g. either purple or white flowers • he also started with varieties that were true-breeding • used plants that produced the same variety of offspring over several generation of self-pollination • e.g. plant that makes white flowers - is true-breeding if ALL the seed from that plant produce white flowers over several generations • we know this is know called homozygous

6. 3 2 1 4 5 TECHNIQUE • in a typical experiment: Mendel mated two contrasting, true-breeding varieties • a process called hybridization • called the true-breeding parents the P generation • the hybrid offspring of the P generation were called the F1 generation • when F1 individuals either self-pollinated or cross- pollinate with other F1 hybrids  the F2 generation Parentalgeneration(P) Stamens Carpel RESULTS First filialgenerationoffspring(F1)

7. EXPERIMENT The Law of Segregation P Generation (true-breedingparents) Purpleflowers Whiteflowers • when Mendel crossed true-breeding white- and purple-flowered pea plants all of the F1 hybrids were purple (100%) • when Mendel crossed these F1 hybrids  many of the F2 plants had purple flowers • but some had white flowers • Mendel discovered a three to one ratio of purple to white flowers in the F2 generation F1 Generation(hybrids) All plants had purple flowers Self- or cross-pollination F2 Generation 705 purple-floweredplants 224 whitefloweredplants

8. Mendel reasoned that only the purple flower factor was affecting flower color in the F1 hybrids • called the purple flower color a dominant trait • the white flower color a recessive trait • the factor for white flowers was not diluted or destroyed because it reappeared in the F2 generation • Mendel observed the same pattern of inheritance in six other pea plant characters - each represented by two traits • what Mendel called a “heritable factor” is what we now call a gene

9. Mendel’s Model • Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspring • Four related concepts make up this model • these concepts can be related to what we now know about genes and chromosomes

10. Concept #1: Alleles Allele for purple flowers • alternative versions of genes account for variations in inherited characters • e.g. the gene for flower color in pea plants exists in two versions: one for purple flowers and the other for white flowers • these alternative versions of a gene are now called alleles • each gene resides at a specific locus on a specific chromosome • because we are diploid – the genetic locus is represented twice • one allele is found on each chromosome in the homologous pair • the same locus for each allele Pair ofhomologouschromosomes Locus for flower-color gene Allele for white flowers

11. Concept #2: Two Alleles are inherited • for each character - an organism inherits two alleles • one from each parent • Mendel made this deduction without knowing about the role of chromosomes • the two alleles at a particular locus may be identical • as in the true-breeding plants of Mendel’s P generation • now known as homozygous • Or the two alleles at a locus may differ • as in the F1 hybrids • now known as heterozygous

12. Concept #3: Dominant vs. Recessive Alleles • if the two alleles at a locus differ- then one determines the organism’s appearance, and the other has no noticeable effect on appearance • the one that determines the appearance – dominant allele • the one that has no effect – recessive allele • we now call the appearance – the phenotype • the genotype – genetic makeup for that trait found in the organism • in the flower-color example- the F1 plants had purple flowers because the allele for that trait is dominant

13. Concept #4: Law of Segregation • two alleles for a heritable character separate or segregate during gamete formation and end up in different gametes • an egg or a sperm gets only one of the two alleles that are present in the organism • this segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis • in the law of independent assortment – this segregation is random

14. Mendel derived the law of segregation by following a single character • the F1 offspring produced Mendel’s first sets of experiments were monohybrids = individuals that are heterozygous for one character • heterozygous for two characters = dihybrids • a cross between such heterozygotes is called a monohybrid cross

15. P Generation Appearance: White flowers Purple flowers Genetic makeup: pp PP p Gametes: P • Mendel’s segregation model accounts for the 3:1 ratio he observed in the F2 generation • the possible combinations of sperm and egg can be shown using a Punnett square • a diagram for predicting the results of a genetic cross between individuals of known genetic makeup • a capital letter represents a dominant allele and a lowercase letter represents a recessive allele F1 Generation Appearance: Purple flowers Genetic makeup: Pp p 1/2 1/2 P Gametes: Sperm from F1 (Pp) plant F2 Generation p P P Pp PP Eggs from F1 (Pp) plant p pp Pp 3 : 1

16. TECHNIQUE The Testcross Dominant phenotype,unknown genotype:PP or Pp? Recessive phenotype,known genotype:pp • How can we tell the genotype of an individual with the dominant phenotype? • such an individual could be either homozygous dominant or heterozygous • the answer is to carry out a testcross: breeding themystery individual with a homozygous recessive individual • if any offspring display the recessive phenotype - the mystery parent must be heterozygous Predictions If purple-floweredparent is PP or If purple-floweredparent is Pp Sperm Sperm p p p p P P Pp Pp Pp Pp Eggs Eggs P p pp pp Pp Pp RESULTS or All offspring purple 1/2 offspring purple and1/2 offspring white

17. The Law of Independent Assortment YYRR yyrr P Generation • Mendel identified his second law of inheritance by following two characters at the same time • crossing two true-breeding parents differing in two characters produces dihybrids in the F1 generation • heterozygous for both characters • a dihybrid cross = a cross between F1 dihybrids • can determine whether two characters are transmitted to offspring as a package or independently • if two traits are linked – 3:1 F2 ratio • if two traits segregate independently – 9:3:3:1 ratio Gametes yr YR F1 Generation YyRr Hypothesis ofdependent assortment Predictions Hypothesis ofindependent assortment Sperm or Predictedoffspring ofF2 generation 1/4 1/4 1/4 1/4 yR yr Yr YR Sperm 1/2 YR 1/2 yr 1/4 YR YYRR YYRr YyRR YyRr 1/2 YR YyRr YYRR 1/4 Yr Eggs YYRr YYrr Yyrr YyRr Eggs 1/2 yr YyRr yyrr 1/4 yR YyRr yyRr YyRR yyRR 3/4 1/4 yr 1/4 Phenotypic ratio 3:1 Yyrr yyRr YyRr yyrr 3/16 3/16 1/16 9/16 Phenotypic ratio 9:3:3:1 approximately 9:3:3:1 108 101 315 32

18. using a dihybrid cross - Mendel developed the law of independent assortment • states that each pair of alleles segregates independently of each other pair of alleles during gamete formation • strictly speaking- this law applies only to genes on different, nonhomologous chromosomes or those far apart on the same chromosome • genes located near each other on the same chromosome tend to be inherited together • tend to be linked

19. Rr Rr  Segregation ofalleles into sperm Segregation ofalleles into eggs The laws of probability govern Mendelian inheritance Sperm • Mendel’s laws of segregation and independent assortment reflect the rules of probability • when tossing a coin -the outcome of one toss has no impact on the outcome of the next toss • in the same way, the alleles of one gene segregate into gametes independently of another gene’s alleles r 1/2 1/2 R R R r R R 1/2 1/4 1/4 Eggs r r r R 1/2 r 1/4 1/4

20. The Multiplication and Addition Rules Applied to Monohybrid Crosses • the multiplication rule states that the probability that two or more independent events will occur together is the productof their individual probabilities • one event and another event will occur • e.g. chances of drawing a king (4/52 or 1/13) and it being a heart (13/52 or 1/4) = 1/52 • probability in an F1 monohybrid cross can be determined using the multiplication rule • segregation in a heterozygous plant is like flipping a coin: • each gamete has a 50% chance (1 out of 2 or ½) of carrying the dominant allele and a 50% chance of carrying the recessive allele

21. the addition rule states that the probability that any one of two or more mutually exclusive events (i.e. “either or” events) will occur is calculated by adding together their individual probabilities • one event or another event will occur • e.g. draw a king or a seven from a deck of cards = 1/13 + 1/13 = 2/13 • the rule of addition can be used to figure out the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous

22. P Generation Appearance: White flowers Purple flowers Genetic makeup: pp PP p Gametes: P • you can also use the multiplication rule on the F2 generations • Pp x Pp monohybrid cross • using a Punnett square – the multiplication rule determines the genotypic frequency of each of the different offspring • ½ of the gametes are P, ½ the gametes are p • ¼ of the offspring are PP, ¼ offspring are pp, ½ the offspring are Pp • but the addition rule gives you the total genotypic makeup or the phenotypic probability within all offspring F1 Generation Appearance: Purple flowers Genetic makeup: Pp p 1/2 1/2 P Gametes: Sperm from F1 (Pp) plant F2 Generation p P P Pp PP Eggs from F1 (Pp) plant p pp Pp 3 : 1

23. Solving Complex Genetics Problems with the Rules of Probability • a dihybrid or other multicharacter cross is equivalent to two or more independent monohybrid crosses occurring simultaneously • in calculating the chances for various genotypes- each character is considered separately and then the individual probabilities are multiplied

24. YYRR yyrr P Generation • multiplication and additional rules are also used for dihybrid F1 crosses • multiplication rule gives you the changes for each offspring = ¼ x ¼ • the chance of a YyRR offspring showing up from a YyRr x YyRr F1 cross • gametes possibilities are all ¼ probabilities • two YyRR offspring are found in the Punnett square – 1/16 + 1/16 = 2/16 or 1/8 • chances of a yellow plant being made • genotypes: YYxx or Yyxx • 9/16 + 3/16 = 12/16 • chances of a yellow,round plant being made • genotypes: YYRR or YyRr or YyRR or YYRr Gametes yr YR F1 Generation YyRr Hypothesis ofdependent assortment Predictions Hypothesis ofindependent assortment Sperm or Predictedoffspring ofF2 generation 1/4 1/4 1/4 1/4 yR yr Yr YR Sperm 1/2 YR 1/2 yr 1/4 YR YYRR YYRr YyRR YyRr 1/2 YR YyRr YYRR 1/4 Yr Eggs YYRr YYrr Yyrr YyRr Eggs 1/2 yr YyRr yyrr 1/4 yR YyRr yyRr YyRR yyRR 3/4 1/4 yr 1/4 Phenotypic ratio 3:1 Yyrr yyRr YyRr yyrr 3/16 3/16 1/16 9/16 Phenotypic ratio 9:3:3:1 approximately 9:3:3:1 108 101 315 32

25. Tri-hybrid cross In calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied 1/4 (probability of pp)  1/2 (yy)  1/2 (Rr)  1/16 ppyyRr  1/16 ppYyrr 1/41/21/2  2/16 Ppyyrr 1/21/21/2  1/16 1/41/21/2 PPyyrr ppyyrr  1/16 1/41/21/2  6/16 or 3/8 Chance of at least two recessive traits

26. Inheritance patterns are often more complex than predicted by simple Mendelian genetics • the relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied • many heritable characters are not determined by only one gene with two alleles • However, the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance

27. Extending Mendelian Genetics for a Single Gene • inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations: • when alleles are not completely dominant or recessive = Incomplete Dominance (or blending) • when a gene has more than two alleles = multi-allelic • when a gene produces multiple phenotypes

28. P Generation Degrees of Dominance White Red CWCW CRCR Gametes CW CR • Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical • Incomplete dominance = the phenotype of F1 hybrid is somewhere between the phenotypes of the two parental varieties • Codominance = two dominant alleles affect the phenotype in separate, distinguishable ways F1 Generation Pink CRCW 1/2 1/2 CR CW Gametes Sperm F2 Generation 1/2 1/2 CW CR 1/2 CR CRCR CRCW Eggs 1/2 CW CRCW CWCW

29. The Relation Between Dominance and Phenotype • a dominant allele does not subdue a recessive allele - alleles don’t interact that way • alleles are simply variations in a gene’s nucleotide sequence • for any character- dominance/recessiveness relationships of alleles depend on the level at which we examine the phenotype • round vs. wrinkled pea shape • dominant allele (round) codes for an enzyme that helps convert an unbranched form of starch into a branched form in the seed • the recessive allele (wrinkled) codes for a defective form and the starch remains unbranched – excess water enters the pea and when it dries it wrinkles • in heterozygotes – one dominant allele makes enough normal enzyme to prevent this from happening = Incomplete Dominance when examined at a closer level

30. The Relation Between Dominance and Phenotype • Tay-Sachsdisease is fatal; a dysfunctional enzyme causes an accumulation of lipids in the brain • At the organismal level, the allele is recessive – disease only shows up if the genotype is homozygous recessive • At the biochemical level, the alleles are incompletely dominant – the amount of lipid coating the neurons is intermediate between the normal individual and the affected individual • no disease manifests itself • the enzyme level in a heterozygote is half the level of a normal individual • At the molecular level, the alleles are codominant – the heterozygote produces a 50:50 ratio of normal to abnormal enzymes

31. Frequency of Dominant Alleles • dominant alleles are not necessarily more common in populations than recessive alleles • for example, one baby out of 400 in the United States is born with extra fingers or toes • the allele for this unusual trait is dominant to the allele for the more common trait of five digits per appendage • in this example, the recessive allele is far more prevalent than the population’s dominant allele • prevalance in the population initially determine via natural selection

32. (a) The three alleles for the ABO blood groups and their carbohydrates Multiple Alleles Allele IA IB i • most genes exist in populations in more than two allelic forms • e.g. the four phenotypes of the ABO blood group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i. • the enzyme encoded by the IA allele adds the A carbohydrate, whereas the enzyme encoded by the IB allele adds the B carbohydrate; the enzyme encoded by the i allele adds neither – type O none Carbohydrate B A (b) Blood group genotypes and phenotypes Genotype ii IAIA or IAi IBIB or IBi IAIB Red blood cellappearance Phenotype(blood group) A AB O B

33. Pleiotropy • most genes have multiple phenotypic effects • a property called pleiotropy • e.g. pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases - such as cystic fibrosis and sickle-cell disease

34. Extending Mendelian Genetics for Two or More Genes • Some traits may be determined by two or more genes • known as multi-allelic • Polygenic inheritance • Epistasis • Complementary

35. Epistasis BbEe BbEe Sperm 1/4 1/4 1/4 1/4 Be BE be bE Eggs • epistasis - a gene at one locus alters the phenotypic expression of a gene at a second locus • e.g. Labrador retrievers and many other mammals - coat color depends on two genes • one gene determines the pigment color • with alleles B for black and b for brown • the other gene determines whether the pigment will be deposited in the hair • with alleles C for color and c for no color 1/4 BE BbEE BBEe BbEe BBEE 1/4 bE BbEE bbEe bbEE BbEe 1/4 Be BBEe BBee Bbee BbEe 1/4 be BbEe bbEe bbee Bbee : 3 9 : 4

36. Polygenic Inheritance AaBbCc AaBbCc Sperm 1/8 1/8 1/8 1/8 1/8 1/8 1/8 1/8 1/8 • Quantitative characters = those that vary in the population along a continuum • quantitative variation usually indicates polygenic inheritance • an additive effect of two or more genes on a single phenotype • skin color in humans is the best example of polygenic inheritance 1/8 1/8 1/8 Eggs 1/8 1/8 1/8 1/8 Phenotypes: 1/64 6/64 15/64 20/64 6/64 1/64 15/64 Number ofdark-skin alleles: 1 2 3 4 5 0 6

37. Nature and Nurture: The Environmental Impact on Phenotype • another departure from Mendelian genetics arises when the phenotype for a character depends on environment as well as genotype • norm of reaction is the phenotypic range of a genotype influenced by the environment • e.g. hydrangea flowers of the same genotype range from blue-violet to pink – depend also on soil acidity in addition to their genotypes • norms of reaction are generally broadest for polygenic characters • such characters are called multifactorial because genetic and environmental factors collectively influence phenotype An organism’s phenotype reflects its overall genotype and unique environmental history

38. Many human traits follow Mendelian patterns of inheritance • Humans are not good subjects for genetic research • Generation time is too long • Parents produce relatively few offspring • Breeding experiments are unacceptable • However, basic Mendelian genetics endures as the foundation of human genetics

39. Pedigree Analysis • but the behavior of genes and their pattern of inheritance can be studied in humans using a pedigree chart • apedigree chartis a family tree that describes the interrelationships of parents and children across generations • inheritance patterns of particular traits can be traced and described using pedigrees • pedigrees can also be used to make predictions about future offspring • we can use the multiplication and addition rules to predict the probability of specific phenotypes within a pedigree chart

40. Key Affected female Mating Male Affectedmale Female Offspring 1stgeneration Ff ff Ff Ff 1stgeneration Ww ww ww Ww 2ndgeneration 2ndgeneration ff ff ff Ff FF or Ff Ff Ww ww ww Ww Ww ww 3rdgeneration 3rdgeneration ff FForFf WWorWw ww • 3rd generation: one daughter doesn’t have a widow’s peak • yet both parents are heterozygotes and possess the trait (peak) • pattern of inheritance – hypothesis that the trait is due to a dominant allele • 3rd generation: one daughter with attached earlobes, the other with a free earlobe • both parents are heterozygotes yet lack this trait • hypothesis supports the recessive allele theory No widow’speak Freeearlobe Widow’speak Attachedearlobe b) (a) Is an attached earlobe a dominantor recessive trait? Is a widow’s peak a dominant orrecessive trait?

41. Recessively Inherited Disorders Parents NormalAa NormalAa • many genetic disorders are inherited in a recessive manner • these range from relatively mild to life-threatening • recessively inherited disorders show up only in individuals homozygous for the allele • Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal • most individuals with recessive disorders are born to carrier parents • e.g. albinism is a recessive condition characterized by a lack of pigmentation in skin and hair Sperm a A Eggs Aa Normal(carrier) AA Normal A Aa Normal(carrier) aa Albino a

42. If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low • Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele • most societies and cultures have laws or taboos against marriages between close relatives

43. Cystic Fibrosis • Cystic fibrosis is the most common lethal genetic disease in the United States • one out of every 2,500 people of European descent • the cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes - leading to a buildup of chloride ions outside the cell • symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine

44. Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications • Sickle-cell disease affects one out of 400 African-Americans • caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells • homozygous individuals - all hemoglobin is abnormal (sickle-cell) • symptoms include physical weakness, pain, organ damage, and even paralysis • heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer some symptoms • about one out of ten African Americans has sickle cell trait, an unusually high frequency of an allele with detrimental effects in homozygotes • Heterozygotes are less susceptible to the malaria parasite, so there is an advantage to being heterozygous

45. Dominantly Inherited Disorders Parents DwarfDd Normaldd • Some human disorders are caused by dominant alleles • Dominant alleles that cause a lethal disease are rare and arise by mutation • Achondroplasia is a form of dwarfism caused by a rare dominant allele Sperm d D Eggs Dd Dwarf dd Normal d dd Normal Dd Dwarf d

46. Huntington’s Disease: A Late-Onset Lethal Disease • The timing of onset of a disease significantly affects its inheritance • Huntington’s disease is a degenerative disease of the nervous system • The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age • Once the deterioration of the nervous system begins the condition is irreversible and fatal

47. Multifactorial Disorders • Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and environmental components • Little is understood about the genetic contribution to most multifactorial diseases

48. Genetic Testing and Counseling • Genetic counselors can provide information to prospective parents concerned about a family history for a specific disease • Using family histories, genetic counselors help couples determine the odds that their children will have genetic disorders • Probabilities are predicted on the most accurate information at the time; predicted probabilities may change as new information is available • based on Mendelian genetics

49. Tests for Identifying Carriers • For a growing number of diseases, tests are available that identify carriers and help define the odds more accurately • In amniocentesis, the liquid that bathes the fetus is removed and tested • In chorionic villus sampling (CVS), a sample of the placenta is removed and tested • Other techniques, such as ultrasound and fetoscopy, allow fetal health to be assessed visually in utero

50. 3 2 1 1 2 (a) Amniocentesis (b) Chorionic villus sampling (CVS) Ultrasound monitor Ultrasoundmonitor Amnioticfluidwithdrawn Fetus Placenta Suctiontubeinsertedthroughcervix Fetus Chorionic villi Placenta Cervix Uterus Cervix Uterus Centrifugation Several hours Fluid Several hours Biochemicaland genetictests Fetal cells Fetal cells Severalweeks Several hours Several weeks Karyotyping