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Transcript
Prior history To appreciate Mendels work, one must keep in mind the prevailing theories of inheritance Mendel ignored development, focused solely on transmission of traits 1 Darwin and Heredity Darwin: Among individuals of any species, there are differences (variations) Evolution cannot occur unless there are differences among individuals Variation is important Mechanism of inheritance is important for understanding evolution Mechanism of inheritance not understood 2 Pangenesis Pangenesis: (1860s) Whole organism reproduces itself Gemmules Germ cells contain gemmules Fertilization- gemmules unite 3 Cytology: Cytology 1600s Organisms are composed of cells 1830s The most distinct structure in a cell is the nucleus. ALL cells have a nucleus. 1840s Cells are formed by the division of preexisting cells (Mitosis) 1850s Sperm and Ovum are cells. 1873 Mitosis described in detail 1883 Fertilization in sea urchin 1885 Meiosis described Reductional division 4 Cytology’s contribution prior to Mendel Heredity is a consequence of genetic continuity of cells by division Germ cells are the vehicle of transmission from one generation to the next Nucleus is crucial. Fertilization involves union of sperm and eggs Fertilization involves union of nuclei Chromosomes do not lose their individuality. Germ cells contain half the number of chromosomes found in body cells. Diploid embryo descends from maternal/paternal fusion of haploid chromosome groups 5 The origin of genetics: The study of genetics begins when Gregor Mendel, in 1865, addressed the question : "How are characters passed on from one generation to the next?” Mendel was the first to make a serious attempt of experimentally answering the question of heredity and not only were his answers correct, they were a complete and compelling proof. Mendel published in 1866 but little attention was paid to his work until 1900, when it was simultaneously rediscovered by three scientists, one in Holland, one in Austria, and one in Germany. There are often impressions that Mendel was removed from the scientific community, or that his papers were not well circulated. This was not true. Over 200 copies of Mendels papers have been discovered in different libraries. All three of Mendel's rediscovers had read Mendel's work prior to publishing their own work. 6 Gregor Mendel was born on either 20th or 22nd July, 1822 in Heizendorf (today Hynice in the Czech Republic). From 1851 to 1853, Gregor Mendel studied zoology, botany, chemistry, and physics at the University of Vienna. He studied botany under Prof. Unger where he learned crosses He studied physics under Prof. Doppler where he learnt statistics Mendel returned to Brno and began his experiments with the hybrid cultivation of pea plants in 1856. After spending eight years carrying out experimental work in the monastery garden, he reported on the results of his observations at the meetings of the Association for Natural Research in Brno on the evenings of February 8th and March 8th, 1865 7 Model organisms A model organism is Model organisms are used to obtain information about other species – including humans – that are difficult to study directly. Genetic model organisms Experimental model organisms Genomic model organisms 8 Model organisms Human model organisms Relevance of model organisms to humans. Modern genetics: 9 The Pea Mendel chose the common garden pea to study patterns of inheritance. This was a excellent choice as a model system for the following reasons: 1 2 3 4 He identified over 20 traits and studied 7 Seed shape: Seed color: Flower color: Pod shape: Pod color: Flower position: Stem length: 10 True breeding The first two years of Mendel's work were devoted to selecting lines that breed true (pure lines) for a particular character or trait. He identified over 20 traits that bred true and studied 7 Breeding True: He identified plants that produced only round seeds and plants that produced only wrinkled seeds. He identified plants that produced only purple flowers and plants that produced only white flowers. 11 Mendel’s first cross P F1 F2 12 Mendel’s first cross P F1 F2 13 Keys to success He did these experiments with all seven traits!!!! The ratios obtained were between 2.82:1 and 3.15:1 This cross involving only one character, seed color, is called a monohybrid cross. Keys to success: 1 2 3 14 Conclusions Although others were doing similar experiments at the time, Mendel work was unique Results and Conclusions: 1 2 3 15 Mendels monohybrid cross YY x yy Yy x Yy 1YY:2Yy:1yy 16 Results and Conclusions: 1 In F1 all progeny showed the same trait for all crosses 2 Males and females was not important 3 Character missing in F1, reappeared in F2 Traits did not blend in the offspring but were transmitted in a discrete fashion and remained unchanged. Reciprocal crosses produced the same results, this indicated that each parent makes an equal contribution to genetic makeup of the offspring. 17 All F1 seeds were yellow but when selfed the F2 produced some green seeds. Mendel termed the trait that is expressed in the F1 as dominant The trait that is hidden but re-expressed in the F2 as recessive. The F1 plants must contain factors for green and yellow since both are found in the F2. With these assumptions the simplest model is that the F1 contains two hereditary factors One for green and another for yellow 18 The parents have two factors, they produce gametes containing only a single factor Parent YY Gamete 1/2Y F1 yy 1/2Y 1/2y 1/2y 1/2Y 1/2y Sperm and egg randomly combine to produce F2 progeny Mendel reasoned that without a mechanism to halve the number of factors in each generation, that factors would multiply with each generation and become unmanageable. Mendel reasoned that during gamete formation the paired factors separate and each gamete receives one of the two factors. 19 Terms Phenotype and genotype: The parental yellow pea plants are a pure line- they only produce yellow pea plants when selfed. Same is true for green However the F1 yellow pea plants produce some green pea plants when selfed. These F1 yellow plants are different from the parental yellow plants. Therefore it is necessary to make the distinction between the appearance of an organism and its genetic make-up. Phenotype refers to appearance of an organism to the eye. Genotype refers its genetic makeup. Would say the parental yellow pea plants and F1 yellow pea plants have the same phenotype but a different genotype. P F1 20 Terms: Dominant and recessive: All F1 seeds were yellow but when selfed the F2 produced some green seeds. Mendel termed the trait that is expressed in the F1 as dominant The trait that is hidden but re-expressed in the F2 as recessive. The F1 plants must contain factors for green and yellow since both are rediscovered in the F2. From the fact the reciprocal crosses produce the same result, Mendel concluded that male and females contribute equally With these assumptions the simplest model is that the F1 contains two hereditary factors One for green and another for yellow Mendel used the Uppercase Y to represent the dominant yellow factor and the lower case y to represent the recessive green. 21 The Principle of Segregation: Mendel reasoned that without a mechanism to halve the number of factors in each generation, that factors would multiple with each generation and become unmanageable. Mendel reasoned that during gamete formation the paired factors separate and each gamete receives one of the two factors. Parent Gamete F1 Notice that while the parents have two factors, they produce gametes containing only a single factor 22 YY Yellow yy Green Grows into A plant Grows into A plant Generates Gametes Generates Gametes Y Or Y y Or y Gametes combine at Random Yy Yellow 23 Mendel's assumption of two factors and segregation makes a strong prediction concerning the genetic make-up of the of F2 yellow pea plants: F1 Y Yy X y Yy Y y 24 Selfing Of the yellow F2 plants, 1/3 should be YY and 2/3 Yy How would you test this prediction? Mendel selfed each of the green F2 plants 25 Selfing Mendel selfed each of the green F2 plants Green yy F3 X X Green yy yy green All green plants 120 green F2 were selfed:120 green seen 26 Selfing Mendel selfed each of the yellow F2 plants 27 Probability Cross Yy x Yy pea plants. Chance of Y sperm uniting with a Y egg ___chance of sperm with Y allele ___ chance of egg with Y allele Chance of Y and Y uniting = = Chance of Yy offspring ___ chance of sperm with y allele and egg with Y allele ___ chance of sperm with Y allele and egg with y allele Chance of Yy = ( x ) + ( x ) = 28 Probability Cross Yy xYy pea plants. Chance of Y sperm uniting with a Y egg (1/2) chance of sperm with Y allele (1/2) chance of egg with Y allele (1/2) Chance of Y and Y uniting = 0.5 x 0.5 = (1/4) Chance of Yy offspring 1/4 chance of sperm with y allele and egg with Y allele 1/4 chance of sperm with Y allele and egg with y allele Chance of Yy = (0.5x0.5) + (0.5x0.5) = 0.5 29 Test cross If instead of selfing the F2 plants, they are crossed to pure breeding green plants, what are the expected outcomes: F2 30 More terms: Mendel's factors are now known as genes Alternative forms of a gene that determine different traits are known as __________ Individuals with two identical alleles are said to be __________ Individuals with two different forms of alleles are said to be _____________ 31 The dihybrid cross and the principle of independent assortment: In the second set of experiments Mendel investigated the pattern of inheritance for two sets of characters simultaneously. A cross involving two sets of characters is called a dihybrid cross. Pea shape: smooth, wrinkled (Smooth is dominant to wrinkled) Cotyledons color: yellow, green (Yellow is dominant to green) P x F1 selfed F2 32 The 9:3:3:1 ratio. The 9:3:3:1 ratio is a lot more complex than the 3:1 ratios of the monohybrid crosses. Mendel's insight was to realize the 9:3:3:1 ratio is nothing more than two 3:1 ratios combined at random. That is if one examined the traits individually they formed a 3:1 ratio. To determine the mode of inheritance of the two genes in this dihybrid cross Mendel examined each of the traits separately: 33 9:3:3:1 ----> 3:1 If we examine only seed shape (smooth, wrinkled) and ignore cotyledon color (yellow, green), in the F2, we expect to find: 3/4 smooth and 1/4 wrinkled: # Smooth = #wrinkled = In addition, if we only examine cotyledon color, we expect 3/4 Yellow to 1/4 green. #Yellow = #green = 34 Each trait behaves as a standard recessive found in a monohybrid cross. They do not affect one another Genes segregate independently!!!! GeneA in a gamete does not affect the segregation of geneB in that gamete. Parent Gamete F1 35 In a heterozygous individual (self cross) SsYy x SsYy Genes line up in two ways during gamete formation Gamete 36 In a heterozygous individual with two traits SsYy x SsYy Genes line up in two ways during gamete formation giving rise to 4 different gametes SsYy SsYy SY sy Gamete Sy sY or SY sy Sy sY 25% 25% 25% 25% Mendel concluded that SsYy individuals produced the following 37 gametes in a 1:1:1:1 ratio SY Sy sY sy Independent assortment If independent assortment is occurring, four different kinds of gametes will be produced in equal frequencies. The only rule is that S and s segregate to separate gametes and Y and y segregate to separate gametes; (that is one does not get an Ss gamete or a Yy gamete) SsYy males and SsYy females can produce four types of gametes in equal frequencies: SY, Sy, sY, sy The male and female gametes randomly combine to restore diploidy 38 Mendels dihybrid cross YYSS x yyss YySs x YySs 9Y-S-:3Y-ss:3yyS-:1yyss Different gene pairs assort independently during gamete formation. The presence of a Y in a gamete does not influence the probability of a S or s being in that gamete. 39 Calculation A heterozygous Red eyed curly winged female fly is crossed to a heterozygous Red eyed curly winged male fly. What is the expected ratio for a Red eyed flat winged male fly? 40 Punnet diagram of a dihybrid cross 41 Branched Diagram If you combine the monohybrid ratios for two PHENOTYPES you get: 3/4 smooth 1/4 wrinkled 42 Probability Yellow is dominant to green Smooth is dominant to wrinkled Heterozygous yellow Heterozygous smooth X Heterozygous yellow Homozygous wrinkled Probability of yellow wrinkled? smooth yellow wrinkled green Heterozygous yellow Homozygous smooth X Heterozygous yellow Homozygous wrinkled Probability of yellow wrinkled? smooth yellow wrinkled 43 More probabilities Yellow is dominant to green Smooth is dominant to wrinkled Tall is dominant to short Heterozygous yellow Heterozygous smooth Heterozygous tall X Heterozygous yellow Homozygous wrinkled Heterozygous tall Probability of green wrinkled short? smooth green tall wrinkled short 44 What is the biological significance of the 9:3:3:1 ratio? This ratio is only produced if TWO DIFFERENT GENE PAIRS assort independently of each other during gamete formation. The presence of one gene in a gamete does not influence the probability of another gene being found in that gamete Principle of segregation: for one gene, each individual has two copies. These two copies segregate from one another during gamete formation. Independent assortment: Segregation of one gene pair is independent of the segregation of any other pair of gene. Hence the 9:3:3:1 ratio and the biological significance of Mendel's second lawDifferent gene pairs assort independently during gamete formation. The presence of a Y in a gamete does not influence the probability of a S or s being in that gamete. 45 Mendels laws 1. The principle of segregation: Each individual carries two copies of a given gene and these segregate from one another during gamete formation. 2. The principle of independent assortment: The segregation of one pair of genes is independent of the segregation of any other pair of genes during gamete formation (as we will find their are important exceptions to this rule)!!!!! By applying these rules Mendel concluded that SsYy individuals produced the following gametes in a 1:1:1:1 ratio SY Sy sY sy As described above, he inferred these gamete ratios by selfing SsYy individuals. He could also have inferred these gamete ratios by crossing SsYy individuals to ssyy individuals. Crossing to the homozygous recessive individuals is known as a test cross 46 Test cross A test cross is easier that a self cross for the F2 What are the expected genotypic and phenotypic ratios of the progeny produced from this cross? 47 Gene number Power of Mendel phenotype ratios: The ratio tells you the number of genes involved in determining a phenotype 3;1 ratio (selfing) = 1 gene 9:3:3:1 ratio (selfing) = 2 genes 27:9:9:9:3:3:3:1 ratio (selfing) = 3 genes Say seed color is controlled by two genes- GeneS and GeneT Green seeds are sstt All others are yellow ( if either S or T are present, the seed is yellow) True breeding yellow SSTT x F1 SsTt (yellow) SsTt Self x true breeding green sstt SsTt How many green will you get out of this cross: These conclusions about gene number become very important when applied to human traits like size, behavior, temperament etc. 48 Take two individuals They both have blue eyes They mate and produce 16 progeny 12 have blue eyes and 4 have black eyes There is ________ gene/s for eye color If instead you get 15 with blue eyes and 1 with black eyes There are _______ gene/s for eye color 49 Dog genome The Dog Genome Project is an example of how basic Mendelian principles are being used to identify genes that control morphology and behavior. Dr. Jasper Rine at U.C. Berkeley crossed Newfoundlands to Border Collies. These dogs differ extensively in size and behavior. Newfoundlands are vigorous swimmers and weight about 140 pounds Border Collies are herders and weigh about 50 pounds By performing a series of Mendelian crosses one can begin to determine how many and what kinds of genes are involved in determining their behavior!!!! Follow the link to Jasper's Dog genome web site (key words dog genome will get you there) 50 Dogs have been breed for specific traits for 10,000 years About 150 breeds have been generated through selective breeding Diversity in Physical makeup: Coat color height mass muscle Behavior: herding tracking retrieval Guarding Intelligence: The individual breeds can mate with one another and produce viable fertile offspring They can also mate with Cayotes and wolves Border collies do not like water, Newfoundlands love water. In the cross swimming is dominant! This complex trait is likely mediated by a small number of genes (~2) 51 Coat color Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes 2 OCTOBER 2009 SCIENCE VOL 326 p150 52 Specific breeds of dogs are also associated with specific diseases Dobermans: narcolepsy Scotties: Haemophilia Terriers: copper metabolism (menke disease) Labrador: hip dysplasia Beagle: seizure risk The ratio from a doberman cross suggests that narcolepsy is most likely mediated by a single gene! (3:1 ratio) Why are Mutts healthier than true breeds? 53 Hybrid Vigor Hybrid vigor: The first cross between two purebred lines is often healthier than either parent 54