Genetics chapter 4 part 2(1)


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Genetics chapter 4 part 2(1)

  1. 1. Gene Interactions { Genetics Chapter 4, Part 2
  2. 2. 4.3 Gene Interaction Modifies Mendelian Ratios • Genes work together to build the complex structures and organ systems of plants and animals • The collaboration of multiple genes in the production of a single phenotypic characteristic or group of related characteristics is termed gene interaction
  3. 3. Representing Alleles • Geneticists use a variety of symbols for alleles • Dominant alleles: – an italic uppercase letter (D) or – letters (Wr) – an italic letter or group of letters with the + superscript (Wr+) • Recessive alleles: – an italic lowercase letter (d) or – an italic letter or group of letters (Wr) Note that the mutant Note that the mutant usually gets the usually gets the letter name! letter name! s / sm / Sm S / Sm / Sm+
  4. 4. Representing alleles in Drosophila • Example: body color – Ebony mutant phenotype is indicated by e – Normal gray (wild-type) is indicated by e+ • e+/e+: gray homozygote (wild type) • e+/e: gray heterozygote (wild type) • e/e: ebony homozygote (mutant) OR • +/+: gray homozygote (wild type) • +/e: gray heterozygote (wild type) • e/e: ebony homozygote (mutant)
  5. 5. Gene Interaction in Pathways • Single-gene trait describes an inherited variation of a gene that can produce a mutant phenotype • However, this is not a complete depiction of genetic reality • Numerous genes contribute to the normal red eye color of Drosophila, including those responsible for production of eye pigments or transport proteins
  6. 6. Three Genes Involved in Drosophila Eye Color • The brown gene produces an enzyme in a pathway that synthesizes a bright red vermilion pigment; mutant flies, bb, have brown eyes • Note: gene named after the mutant, not the gene it encodes for! • The vermillion genes produces an enzyme in a pathway that synthesizes a brown pigment; mutant flies, vv, have bright red eyes • The white gene encodes a transporter that carries pigment to the eye; flies that do not produce this protein have white eyes
  7. 7. Three Distinct Types of Genetic Pathways • Biosynthetic pathways are networks of interacting genes that produce a molecular compound as their endpoint • Signal transduction pathways receive chemical signals from outside a cell and initiate a response inside the cell • Developmental pathways direct growth, development and differentiation of body parts and structures
  9. 9. The One-Gene-One Enzyme Hypothesis • George Beadle and Edward Tatum were among the first to investigate biosynthetic pathways • They studied growth variants of the fungus, Neurospora crassa • Their proposal, the one-geneone enzyme hypothesis came out of their experiments Red Bread Mold;
  10. 10. Beadle and Tatum Experiment Prototroph: an organism that can synthesize all of its amino acids Auxotroph: an organism that has lost the ability to synthesize certain substances required for its growth and metabolism This experiment looked at amino acids, but you could look at other synthetic pathways! CAUSING MUTATION!
  11. 11. The Hypothesis Made a Connection Between Genes, Proteins and Phenotypes • Each gene produces an enzyme • Each enzyme has a specific role in a biosynthetic pathway that produces the phenotype • Each mutant phenotype due to the loss or malfunction of a specific enzyme
  12. 12. Genetic Dissection to Investigate Gene Action • Biosynthetic pathways consist of sequential steps • Completion of one step generates the substrate for the next step in the pathway • Completion of every step is necessary to produce the end product • Genetic dissection is an experimental approach taken to investigate the steps of biosynthetic pathways
  13. 13. Genetic Dissections: Horowitz’s Experiments on Met- Mutants of Neurospora • Horowitz’s analysis aimed to: • Determine the number of intermediate steps in the methionine synthesis pathway • Determine the order of the steps • Identify the step affected by each mutation
  14. 14. Genetic Dissection: Results of Horowitz’s Experiments • Whether or not a mutant strain grows on a medium containing a component of the pathway allows determination of the step at which the mutant is blocked • Mutation of an enzyme will cause the pathway to become blocked. • If we give an intermediate from before the block, we can’t pass the block and the mutant will not grow. • If we give an intermediate after the block, the mutant will grow. • The blocked step is also identified by the substance that accumulates in the auxotroph • Imagine one mutant: Give A, B or C: Won’t grow! X Give D, E or F: Will grow! What Accumulates?
  15. 15. 1. Met 1: only on minimal media + methionine, indicating it is the last step of the pathway. Need to add methionine to get past the block 2. Met 2: need minimal + homocysteine , therefore block is at step that produces homocysteine. This result also tell us that homocysteine is the substrate converted to methionine in the biosynthetic pathway. 3. Met 3: grows on minimal, homocysteine & cystathionine. This tells us that Met 3 is blocked at the step that produces cystathionine and that cystathionine precedes homocysteine 4. Met 4 grows with any supplementation of minimal media. This tells us that Met 4 is defective at a step that precedes the production of cysteine.
  16. 16. More Recent Adjustments to the Hypothesis • Hypothesis confirmed!: Each gene produces an enzyme • Each enzyme has a specific role in a biosynthetic pathway that produces the phenotype • Recent Adjustments: • Some protein producing genes produce transport proteins, structural or regulatory proteins, rather than enzymes • Some genes produce RNAs rather than proteins • Some proteins (e.g. β-globin) must join with other proteins to acquire a function
  17. 17. Gene Interactions So far…  AaBb x AaBb    Crossing genotypes leads to a phenotypic ratio BUT, Genes do not act alone. Now let’s look at how genes interact to alter phenotypic ratios….
  18. 18. Epistasis: Gene Interactions • Epistatic interactions happen when an allele of one gene modifies or prevents the expression of alleles at another gene. • Epistatic interactions often arise because two (or more) different proteins participate in a common cellular function – For example, an enzymatic pathway Colorless precursor Enzyme C The recessive c allele encodes an inactive enzyme Colorless intermediate Enzyme P Purple pigment The recessive p allele encodes an inactive enzyme
  19. 19. No Interaction (9:3:3:1 Ratio) • The expected 9:3:3:1 ratio is seen in the absence of epistasis: when the genes do not interact to change the expression of one another Dihybrid cross, F2 progeny
  20. 20. No Interaction (9:3:3:1 Ratio) • Cross involving the brown and vermillion genes in Drosophila • When pure-breeding brown flies (b/b; v+/v+) are crossed to pure-breeding vermillion flies (b+/b+; v/v), the F1 all have wild type red eyes (b+/b; v+/v) • When the F1 are interbred (b+/b; v+/v x b+/b; v+/v ), the F2 are: • 9/16 b+/-; v+/-, wild type, red eyes • 3/16 b/b; v+/-, brown eyes • 3/16 b+/-; v/v, vermillion eyes • 1/16 b/b;v/v, white eyes • The results show that the genes are not undergoing epistatic interaction with one another
  21. 21. Epistatic Interactions • A minimum of two genes are required for epistatic interactions; these usually participate in the same pathway • There are six ways epistasis could affect the predicted 9:3:3:1 dihybrid ratio
  22. 22. Epistatic Interactions Gene interaction alters the classic 9:3:3:1 ratio seen in the F2 Gene interaction alters the classic 9:3:3:1 ratio seen in the F2 progeny of the dihybrid cross! progeny of the dihybrid cross!
  23. 23. Complementary Gene Interaction (9:7 Ratio) • Bateson and Punnett crossed two pure-breeding strains of white flowered sweet peas • They found all the F1 were purple flowered; the F1 x F1 cross yielded 9/16 purple and 7/16 white flowered progeny • They recognized that the two genes interact to produce the overall flower color; when genes work in tandem to produce a single gene product, it is called complementary gene interaction
  24. 24. Duplicate Gene Action (15:1 Ratio) • The genes in a redundant system have duplicate gene action; they encode the same product, or they encode products that have the same effect in a pathway or compensatory pathways
  25. 25. Dominant Gene Interaction (9:6:1 Ratio) • • Plants that have dominant allele(s) for just one of either of the genes will have round fruit and those with only recessive alleles of both genes will have long fruit Dominant for either gene (A or B), equals one phenotype. (3+3 = 6)
  26. 26. Recessive epistasis (9:3:4) • B and b for black and brown melanin (MC1R gene) • E: controls deposition of pigment in hairs (TRYP1 gene) • ee is epistatic • Recessive epistatsis causes yellow coat color
  27. 27. Recessive epistasis (9:3:4) Brown eumelanin Eumelanin deposition Black eumelanin Not able to deposit! May or may not be correct in your book! May or may not be correct in your book!
  28. 28. Dominant Epistasis (12:3:1 Ratio) • In dominant epistasis, a dominant allele at one locus will mask the phenotypic expression of the alleles at a second locus, giving a 12:3:1 ratio • E.g. in foxglove flowers a dominant allele at one locus restricts the deposition of pigment to a small area of the flower
  29. 29. Dominant Suppression (13:3 Ratio) • • • In dominant suppression, a dominant allele at one locus completely suppresses the phenotypic expression of the alleles at a second locus, giving a 13:3 ratio In chickens, the C allele is responsible for pigmented feathers and the c allele for white feathers The dominant allele of a second gene, I, can suppress the color producing effect of the C allele, leading to white feathers in both C/- and c/c individuals Dominant I Isuppresses dominant Dominant suppresses dominant pigment production pigment production
  30. 30. YOU MUST KNOW FOUNDATION FIGURE 4.21 (p. 130-131!)
  31. 31. 4.4 Complementation Analysis Distinguishes Mutations in the Same Gene from Mutations in Different Genes • When geneticists encounter organisms with the same mutant phenotype, they ask two questions: 1. Do these organisms have mutations in the same or in different genes? 2. How many genes are responsible for the phenotypes observed? Ex. Two botanists working with petunias both discover a white flower Ex. Two botanists working with petunias both discover a white flower mutation. One works in California and one works in the Netherlands. mutation. One works in California and one works in the Netherlands. Are the mutations in the same genes? Are the mutations in the same genes?
  32. 32. We have two Drosophila with the same phenotypic mutation…. HOW DO WE KNOW IF THE GENETIC MUTATION IS THE SAME?
  33. 33. Genetic Complementation Analysis A B • Genetic heterogeneity is when mutations in different genes can produce the same or very similar mutant phenotypes • Mating of two organisms with similar mutant phenotypes can lead to wild type offspring, a phenomenon called genetic complementation • Complementation testing is when two pure breeding organisms with similar mutant phenotypes are mated • If complementation occurs, wild type offspring are obtained and the mutations are known to affect two different genes • When the mutations fail to complement, the offspring have the mutant phenotype and the mutations are known to affect the same gene Example of a complementation test. Two strains of flies are white eyed because of two different autosomal recessive mutations which interrupt different steps in a single pigment-producing metabolic pathway.
  34. 34. Complementation Analysis • In complementation analysis multiple crosses are performed among numerous pure breeding mutants to try to determine how many different genes contribute to a phenotype • Mutations that mutually fail to complement one another are called a complementation group • Can’t get back to wild-type! • Mutation is on the same gene! • A complementation group in this context refers to a gene
  35. 35. Genetic Complementation? Genetic Complementation? -Vermilion vs. White -Vermilion vs. White -Apricot vs. Buff -Apricot vs. Buff
  36. 36. + = cross of pure-breeding mutants yield wild-type (complements) + = cross of pure-breeding mutants yield wild-type (complements) --= cross of pure-breeding mutants yields only mutant progeny = cross of pure-breeding mutants yields only mutant progeny -Mutations that fail to complement each other are on the same gene -Complementation group: consist of one or mutants of a single gene
  37. 37. There are SO many different eye colors for Drosophila! WHAT ARE THE FUNCTIONAL CONSEQUENCES OF MUTATION?
  38. 38. Functional Consequences of Mutation (See Fig. 4.1) • A wild type phenotype is produced when an organism has two copies of the wild type allele • Mutant alleles can be: • Gain-of-function, in which the gene product acquires a new function or express increased wild type activity • Loss-of-function, in which there is a significant decrease or complete loss of functional gene product
  39. 39. Loss-of-Function Mutations Amorphic = no function Amorphic = no function Hypomorphic = less function Hypomorphic = less function
  40. 40. Dominant Negative Mutations • Multimeric proteins, composed of two or more polypeptides that join together to form a functional protein are particularly subject to dominant negative mutations • These are negative mutations due to their “spoiler” effect on the protein as a whole
  41. 41. Gain-of-Function Mutations Hypermorphic = more function Hypermorphic = more function Neomorphic = new function Neomorphic = new function
  42. 42. Questions?