Mendel and the Gene Idea Chapter 14 Mendel and the Gene Idea http://science.discovery.com/tv-shows/greatest-discoveries/videos/100-greatest-discoveries-shorts-genetics.htm

One possible explanation of heredity is a “blending” hypothesis 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 Mendel used the scientific approach to identify two laws of inheritance Mendel discovered the basic principles of heredity by breeding garden peas Vocabulary Character: a heritable feature, such as flower color Trait: a variant of a character, such as purple or white flowers

Mendel also made sure that Mendel chose to track Only those characters that varied in an “either-or” manner Ex: Flower color trait is either purple or white, there is no intermediate Mendel also made sure that He started his experiments with varieties that were “true-breeding” all successive generations display only the desired trait Ex: A purple-flowered plant is self-pollinated and all the offspring have purple flowers

Mendel’s work P F1 F2 Bred pea plants Pollen transferred from white flower to stigma of purple flower Bred pea plants cross-pollinate two true breeding parents (P) hybridization P = parental raised seed & then observed traits (F1) Hybrid offspring F = filial allowed offspring to self-pollinate & observed next generation (F2) P anthers removed P = parents F = filial generation all purple flowers result F1 self-pollinate F2

Looking closer at Mendel’s work true-breeding purple-flower peas true-breeding white-flower peas X P Where did the white flowers go? 100% F1 generation (hybrids) purple-flower peas In a typical breeding experiment, Mendel would cross-pollinate (hybridize) two contrasting, true-breeding pea varieties. The true-breeding parents are the P generation and their hybrid offspring are the F1 generation. Mendel would then allow the F1 hybrids to self-pollinate to produce an F2 generation. White flowers came back! self-pollinate F2 generation 3:1 75% purple-flower peas 25% white-flower peas

Mendel reasoned that In the F1 plants, only the purple flower factor was affecting flower color in these hybrids Purple flower color was dominant, and white flower color was recessive Table 14.1 Mendel observed the same pattern In many other pea plant characters

Mendel’s Experiments and Observations Allowed Mendel to deduce two fundamental laws of heredity: Law of Segregation Law of Independent Assortment

Mendel’s Model Mendel developed a hypothesis To explain the 3:1 inheritance pattern that he observed among the F2 offspring Four related concepts make up this model Alternative versions of genes (alleles) Each Allele is represented twice If two alleles differ, the dominant one is expressed Two alleles segregate during meiosis

What did Mendel’s findings mean? Traits come in alternative versions purple vs. white flower color alleles different alleles vary in the sequence of nucleotides at the specific locus of a gene some difference in sequence of A, T, C, G purple-flower allele & white-flower allele are two DNA variations at flower-color locus different versions of gene at same location on homologous chromosomes

Traits are inherited as discrete units For each characteristic, an organism inherits 2 alleles, 1 from each parent diploid organism inherits 2 sets of chromosomes, 1 from each parent homologous chromosomes A genetic locus is actually represented twice, one on each homolog of a pair of chromosomes Two alleles may be identical or different

What did Mendel’s findings mean? Some traits mask others purple & white flower colors are separate traits that do not blend purple x white ≠ light purple purple masked white dominant allele functional protein masks other alleles recessive allele allele makes a malfunctioning protein I’ll speak for both of us! wild type allele producing functional protein mutant allele producing malfunctioning protein homologous chromosomes

Fourth, the law of segregation PP P Law of segregation during meiosis, alleles segregate homologous chromosomes separate each allele for a trait is packaged into a separate gamete An egg or sperm only receives one of the two alleles present in the somatic cell pp p Pp P p

Law of Segregation Metaphase 1 Which stage of meiosis creates the law of segregation? Metaphase 1 Whoa! And Mendel didn’t even know DNA or genes existed!

Genotype vs. phenotype X Difference between how an organism “looks” & its genetics phenotype description of an organism’s trait the “physical” genotype description of an organism’s genetic makeup F1 P X purple white all purple Explain Mendel’s results using …dominant & recessive …phenotype & genotype

PP pp Pp Making crosses x X Can represent alleles as letters flower color alleles  P or p true-breeding purple-flower peas  PP true-breeding white-flower peas  pp F1 P X purple white all purple PP x pp Pp

Mendel’s law of segregation, probability and the Punnett square Try a cross: Pp x Pp P Generation F1 Generation F2 Generation P p Pp PP pp Appearance: Genetic makeup: Purple flowers PP White flowers pp Purple flowers Pp Gametes: F1 sperm F1 eggs 1/2  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. 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. 3 : 1 Random combination of the gametes results in the 3:1 ratio that Mendel observed in the F2 generation. 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.

Genotypes Homozygous = same alleles = PP, pp True-breeding, all sperm/egg contain P Heterozygous = different alleles = Pp ½ sperm/egg contain P other ½ contains p homozygous dominant Can’t tell by lookin’ at ya! heterozygous How do you determine the genotype of an individual with with a dominant phenotype? homozygous recessive

Test cross pp x is it PP or Pp? Breed the dominant phenotype — the unknown genotype — with a homozygous recessive (pp) to determine the identity of the unknown allele x How does that work? is it PP or Pp? pp

How does a Test cross work? x x Am I this? Or am I this? PP pp Pp pp p p p p P P Pp Pp Pp Pp P p Pp Pp pp pp 100% purple 50% purple:50% white or 1:1

The Law of Independent Assortment Mendel derived the law of segregation By following a single trait The F1 offspring produced in this cross Were monohybrids, heterozygous for one character Crossing two heterozygotes is a monohybrid cross F1 x Pp x Pp

The Law of Independent Assortment Mendel identified his second law of inheritance By following two characters at the same time See color & seed shape Crossing two, true-breeding parents differing in two characters Produces dihybrids in the F1 generation, heterozygous for both characters Y = yellow R = round y = green r = wrinkled P x yyrr YYRR

Phenotypic ratio approximately 9:3:3:1 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 RESULTS CONCLUSION The results support the hypothesis of independent 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. 9:3:3:1 Figure 14.8

What’s going on here? YyRr YyRr YR yr YR Yr yR yr Is it this? Or this? If genes are on different chromosomes… how do they assort in the gametes? together or independently? YyRr Is it this? Or this? YyRr YR yr YR Yr yR yr Which system explains the data?

 Is this the way it works? YyRr x YyRr YR yr YR YYRR YyRr yr YyRr 9/16 yellow round  YR yr 3/16 green round Well, that’s NOT right! YR YYRR YyRr 3/16 yellow wrinkled yr YyRr yyrr 1/16 green wrinkled

 Dihybrid cross YyRr x YyRr YR Yr yR yr YR Yr yR yr YYRR YYRr YyRR or YyRr x YyRr 9/16 yellow round YR Yr yR yr YR Yr yR yr  3/16 green round YYRR YYRr YyRR YyRr BINGO! YYRr YYrr YyRr Yyrr 3/16 yellow wrinkled YyRR YyRr yyRR yyRr 1/16 green wrinkled YyRr Yyrr yyRr yyrr

Mendel’s 2nd law of heredity Using the information from a dihybrid cross, Mendel developed the law of independent assortment Each pair of alleles segregates independently during gamete formation Works for alleles on different chromosomes (chromosomes that are not homologous) Or genes far apart from each other on the same chromosome that frequently cross over

Law of Independent Assortment Which stage of meiosis creates the law of independent assortment? Metaphase 1 EXCEPTION If genes are on same chromosome & close together will usually be inherited together rarely crossover separately “linked”

The chromosomal basis of Mendel’s laws…

Review: Mendel’s laws of heredity Law of segregation monohybrid cross single trait each allele segregates into separate gametes established by Metaphase 1 Law of independent assortment dihybrid (or more) cross 2 or more traits genes on separate chromosomes assort into gametes independently EXCEPTION linked genes

Concept Check 14.1 A pea plant heterozygous for inflated pods (Ii) is crossed with a plant homozygous for constricted pods (ii). Draw a Punnett square for this cross. Pea plants heterozygous for flower position and stem length (AaTt) are allowed to self pollinate, and 400 of the resulting seeds are plants. How many offspring would be predicted to have terminal flowers and be dwarf?

Concept 14.2: The laws of probability govern Mendelian inheritance Mendel’s laws of segregation and independent assortment Reflect the rules of probability The multiplication rule Finding the probability that two or more independent events will occur together: Multiply the probability of one event by the probability of the other even Ex: Probability of 2 offspring from the same parents are both homozygous recessive?

What is the likelihood that an offspring is heterozygote? Probability in a monohybrid cross Can be determined using this rule 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 One or more possibilities that can occur in the same event  Rr Segregation of alleles into eggs alleles into sperm R r 1⁄2 1⁄4 Sperm Eggs Figure 14.9 What is the likelihood that an offspring is heterozygote? ¼ + ¼ = ½ What is the likelihood two offspring from the same parents are both homozygous recessive? ¼ x ¼ = 1/16

Solving Complex Genetics Problems with the Rules of Probability We can apply the rules of probability To predict the outcome of crosses involving multiple characters A dihybrid or other multicharacter cross Is equivalent to two or more independent monohybrid crosses occurring simultaneously In calculating the chances for various genotypes from such crosses Each character first is considered separately and then the individual probabilities are multiplied together

Concept Check 14.2 For any gene with a dominant allele C and recessive allele c, what proportions of the offspring from a CC x Cc cross are expected to be homozygous dominant, homozygous recessive and heterozygous? An organism with the genotype BbDD is mated to one with the genotype BBDd. Assuming independent assortment of these two genes, write the genotypes of all possible offspring from this cross and use the rules of probability to calculate the chance of each type occurring.

The relationship between genotype and phenotype is rarely simple Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian genetics The relationship between genotype and phenotype is rarely simple The inheritance of characters by a single gene May deviate from simple Mendelian patterns

The Spectrum of Dominance Complete dominance Occurs when the phenotypes of the heterozygote and dominant homozygote are identical In incomplete dominance The phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties 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 RR RW WW

Co-dominance 2 alleles affect the phenotype equally & separately not blended phenotype human ABO blood groups Multiple Alleles: 3 alleles IA, IB, i IA & IB alleles are co-dominant glycoprotein antigens on RBC IAIB = both antigens are produced i allele recessive to both

The Relation Between Dominance and Phenotype Dominant and recessive alleles Do not really “interact” Dominant alleles do not “subdue” recessive alleles Lead to synthesis of different proteins that produce a phenotype Ex: Tay Sachs Disease: autosomal recessive inheritance pattern Frequency of Dominant Alleles Dominant alleles Are not necessarily more common in populations than recessive alleles Ex: Polydactyly: occurs in 1 in 400 births; autosomal dominant

Pleiotropy In pleiotropy A gene has multiple phenotypic effects Most genes are pleiotrophic Ex: A genetic disease caused by a single allele has many symptoms associated with it One gene can affect many characteristics in an organism

Extending Mendelian Genetics for Two or More Genes Some traits May be determined by two or more genes This type of expression includes: Epistasis Polygenic Inheritance

Epistasis One gene completely masks another gene coat color in mice = 2 separate genes C,c: pigment (C) or no pigment (c) B,b: more pigment (black=B) or less (brown=b) cc = albino, no matter B allele 9:3:3:1 becomes 9:3:4 B_C_ B_C_ bbC_ bbC_ _ _cc _ _cc How would you know that difference wasn’t random chance? Chi-square test!

Epistasis in Labrador retrievers 2 genes: (E,e) & (B,b) pigment (E) or no pigment (e) pigment concentration: black (B) to brown (b) eebb eeB– E–bb E–B–

Polygenic inheritance Some phenotypes determined by additive effects of 2 or more genes on a single character phenotypes on a continuum human traits skin color height weight intelligence behaviors

Skin color: Albinism However albinism can be inherited as a single gene trait aa = albino enzyme tyrosine albinism melanin

Environmental effects Phenotype is controlled by both environment & genes Multifactorial characters Human skin color is influenced by both genetics & environmental conditions The relative importance of genes & the environment in influencing human characteristics is a very old & hotly contested debate a single tree has leaves that vary in size, shape & color, depending on exposure to wind & sun for humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests even identical twins — genetic equals — accumulate phenotypic differences as a result of their unique experiences Coat color in arctic fox influenced by heat sensitive alleles Color of Hydrangea flowers is influenced by soil pH

Concept Check 14.3 If a man with type AB blood marries a woman with type O blood, what blood types would you expect in their children? A rooster with gray feathers is mated with a hen of the same phenotype. Among their offspring, 15 chicks are gray, 6 are black and 8 are white. What is the simplest explanation for the inheritance of these colors in chickens? What phenotypes would you expect in the offspring of a cross between a gray rooster and a black hen?

Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance data mapped on a family tree = male = female = male w/ trait = female w/ trait

Simple pedigree analysis What’s the likely inheritance pattern? Simple pedigree analysis 1 2 3 4 5 6 1 2 3 4 5 6

Genetic counseling Pedigree can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive traits from benign conditions to deadly diseases albinism cystic fibrosis Tay sachs sickle cell anemia PKU

Recessive diseases A a AA Aa A a Aa aa The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all Heterozygotes (Aa) carriers have a normal phenotype because one “normal” allele produces enough of the required protein A a male / sperm AA Aa A a female / eggs carrier Aa aa carrier disease

Cystic fibrosis (recessive) Primarily whites of European descent strikes 1 in 2500 births 1 in 25 whites is a carrier (Aa) normal allele codes for a membrane protein that transports Cl- across cell membrane defective or absent channels limit transport of Cl- & H2O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections without treatment children die before 5; with treatment can live past their late 20s normal lung tissue Cystic fibrosis is an inherited disease that is relatively common in the U.S. Cystic fibrosis affects multiple parts of the body including the pancreas, the sweat glands, and the lungs. When someone has cystic fibrosis, they often have lots of lung problems. The cause of their lung problems is directly related to basic problems with diffusion and osmosis in the large airways of the lungs. People without cystic fibrosis have a small layer of salt water in the large airways of their lungs. This layer of salt water is under the mucus layer which lines the airways. The mucus layer in the airways helps to clear dust and other inhaled particles from the lungs.

Effect on Lungs Chloride channel Cl– Cl– bacteria & mucus build up transports salt through protein channel out of cell Osmosis: H2O follows Cl– Effect on Lungs normal lungs airway Cl– Cl– channel H2O cells lining lungs In people without cystic fibrosis, working cystic fibrosis proteins allow salt (chloride) to enter the air space and water follows by osmosis. The mucus layer is dilute and not very sticky. In people with cystic fibrosis, non-working cystic fibrosis proteins mean no salt (chloride) enters the air space and water doesn't either. The mucus layer is concentrated and very sticky. People with cystic fibrosis have lung problems because: Proteins for diffusion of salt into the airways don't work. (less diffusion) Less salt in the airways means less water in the airways. (less osmosis) Less water in the airways means mucus layer is very sticky (viscous). Sticky mucus cannot be easily moved to clear particles from the lungs. Sticky mucus traps bacteria and causes more lung infections. Therefore, because of less diffusion of salt and less osmosis of water, people with cystic fibrosis have too much sticky mucus in the airways of their lungs and get lots of lung infections. Thus, they are sick a lot. cystic fibrosis Cl– H2O bacteria & mucus build up thickened mucus hard to secrete mucus secreting glands

Tay-Sachs (recessive) Primarily Jews of eastern European (Ashkenazi) descent & Cajuns (Louisiana) strikes 1 in 3600 births 100 times greater than incidence among non-Jews non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5yo

Sickle cell anemia (recessive) Primarily Africans strikes 1 out of 400 African Americans high frequency caused by substitution of a single amino acid in hemoglobin when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods deforms red blood cells into sickle shape sickling creates pleiotropic effects = cascade of other symptoms

Doctors can use regular blood transfusions to prevent brain damage and new drugs to prevent or treat other problems.

Sickle cell phenotype 2 alleles are codominant both normal & mutant hemoglobins are synthesized in heterozygote (Aa) 50% cells sickle; 50% cells normal carriers usually healthy sickle-cell disease triggered under blood oxygen stress exercise

Dominantly Inherited Disorders Some human disorders Are due to dominant alleles Dominant alleles that cause lethal disease are much less common Ex: achondroplasia: a form of dwarfism that is lethal when homozygous for the dominant allele What is the chance that two married dwarves with achondroplasia would have a child who was of normal height?

Heterozygote advantage Malaria single-celled eukaryote parasite spends part of its life cycle in red blood cells In tropical Africa, where malaria is common: homozygous dominant individuals die of malaria homozygous recessive individuals die of sickle cell anemia heterozygote carriers are relatively free of both reproductive advantage High frequency of sickle cell allele in African Americans is vestige of African roots

Inheritance pattern of Achondroplasia Aa x aa Aa x Aa dominant inheritance a a A a  Aa Aa AA Aa A A dwarf dwarf lethal a aa aa a Aa aa 50% dwarf:50% normal or 1:1 67% dwarf:33% normal or 2:1

Huntington’s chorea (dominant) Dominant inheritance repeated mutation on end of chromosome 4 mutation = CAG repeats glutamine amino acid repeats in protein one of 1st genes to be identified build up of “huntingtin” protein in brain causing cell death memory loss muscle tremors, jerky movements “chorea” starts at age 30-50 early death 10-20 years after start

Multifactorial Disorders Many human diseases Have both genetic and environment components Examples include Heart disease, cancer, diabetes, and alcoholism The hereditary component of these diseases is polygenic

Genetic Testing and Counseling Based on Mendelian Genetics and Probability Rules 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

Tests for Identifying Carriers For a growing number of diseases Tests are available that identify carriers and help define the odds more accurately Tests are available for Tay-Sachs, Sickle Cell Anemia, and Cystic Fibrosis sequence individual genes

Fetal & Newborn Testing 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 (a) Amniocentesis Amniotic fluid withdrawn Fetus Placenta Uterus Cervix Centrifugation A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. (b) Chorionic villus sampling (CVS) Fluid Fetal cells Biochemical tests can be Performed immediately on the amniotic fluid or later on the cultured cells. Fetal cells must be cultured for several weeks to obtain sufficient numbers for karyotyping. Several weeks Biochemical tests hours Chorionic viIIi A sample of chorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. Suction tube Inserted through cervix Karyotyping and biochemical tests can be performed on the fetal cells immediately, providing results within a day or so. Karyotyping