Extensions of Mendelism

Transcription

1 Chapter 4. Extensions of Mendelism 1. Allelic Variation and gene function 2. Gene action : from genotype to phenotype

2 Allelic Variation and gene function Mendel's experiments established that genes can exist in alternate forms. Mendel identified two alleles, one dominant, the other recessive. This discovery suggested a simple functional dichotomy between alleles, as if one allele did nothing and the other did everything to determine the phenotype. However, research early in the twentieth century demonstrated this to be an oversimplification. Genes can exist in more than two allelic states, and each allele can have a different effect on the phenotype.

3 Allelic Variation and gene function Incomplete dominance Codominance Multiple alleles Allelic series Testing gene mutations for allelism Variation among the effect of mutations Gene function to produce polypetides Why are some mutations dominant and others recessive?

4 ALLELIC VARIATION AND GENE FUNCTION An allele is dominant if it has the same phenotypic effect in heterozygotes as in homozygotes that is, the genotypes Aa and AA are phenotypically indistinguishable. Sometimes, however, a heterozygote has a phenotype different from that of either of its associated homozygotes. Flower color in the snapdragon, Antirrhinum majus, is an example.

5 Incomplete dominance Flower color in the snapdragon, Antirrhinum majus Heterozygote has a phenotype different from that of either of its associated homozygotes Depend on the amount of a product made by the color gene The allele for red color (W) is therefore said to be incompletely, or partially, dominant over the allele for white color (w).

6 If the W allele specifies this product and the w allele does not, WW homozygotes will have twice as much of the product as Ww heterozygotes do and will therefore show deeper color. When the heterozygote's phenotype is midway between the phenotypes of the two homozygotes, as it is here, the partially dominant allele is sometimes said to be semidominant (from the Latin word for half thus half-dominant).

7 Another exception: Codominance Human blood types (MN type). One serum, called anti-m, recognizes only the M antigen on human blood cells. Another serum, called anti-n, recognizes only the N antigen on these cells. The two alleles appear to contribute equally the phenotype of the heterozygotes. Discovered by Karl Landsteiner.

8 The ability to produce the M and N antigens is determined by a gene with two alleles. Homozygotes for the M allele produce only the M antigen, and homozygotes for the N allele produce only the N antigen. However, heterozygotes for these two alleles produce both kinds of antigens. Because the two alleles appear to contribute independently to the phenotype of the heterozygotes, they are said to be codominant. Codominance implies that there is an independence of allele function. Neither allele is dominant, or even partially dominant, over the other.

9 Multiple alleles The Mendelian concept that genes exist in no more than two allelic states had to be modified when genes with three, four, or more alleles were discovered. Genes with more than two allelic states are common. Four alleles (c, albino,; ch, himalayan,; cch, chinchilla; c+, wild type) control coat color in rabbits in different ways and are mutants of the c gene. Wild type alleles such as c+ usually refer to the most frequent allele in a population.

10 Multiple alleles Coat color in rabbit - four alleles c : albino c h : himalayan c ch : chinchilla c + : wild type

11 Human blood types (ABO type) - The gene responsible for producing the A and B antigens is denoted by the letter I. - Three alleles : I A, I B, i - I A allele specifies the production of the A antigen - I B allele specifies the production of the B antigen - i allele dose not specify an antigen - The I A and I B alleles are codominant. - i allele is recessive to both I A and I B alleles. - I gene is polymorphic (having many forms)

12 Human blood types (ABO type)

13 Allelic series The functional relationships among the members of a series of multiple alleles can be studied by making heterozygous combination. Four alleles of the c gene in rabbit - make six different kinds of heterozygotes cc h, cc ch, cc +, c h c ch, c h c +, c ch c + - Dominance relation : c + c ch c h c - Null or amorphic : nonfunctional alleles (albino allele) - Hypomorphic : partially functional alleles (chinchilla and himalayan alleles)

14 Testing Gene Mutations for Allelism A mutant allele is created when an existing allele changes to a new genetic state a process called mutation. it is not always possible to assign a new mutation to a gene on the basis of its phenotypic effect. In rabbits, for example, several genes determine coat color, and a mutation in any one of them could reduce, alter, or abolish pigmentation in the hairs. Thus, if a new coat color appears in a population of rabbits, it is not immediately clear which gene has been mutated.

15 A simple test can be used to determine the allelic identity of a new mutation as long as the new mutation is recessive. The procedure involves crosses to combine the new recessive mutation with recessive mutations of known genes.

16 Different recessive alleles can be tested for allelism by crossing homozygous recessives against each other since only if they are allelic will the offspring show the recessive phenotype. If they are wild type, then the alleles are in different genes controlling the same phenotype.

17 Testing gene mutations for allelism A general scheme to test recessive mutations for allelism. Two mutations are alleles if a hybrid that contains both of them has the mutant phenotype.

18 It is important to remember that this test applies only to recessive mutations. Dominant mutations cannot be tested in this way because they exert their effects even if a wild-type copy of the gene is present

19 Testing gene mutations for allelism A test for allelism involving recessive eye color mutations in Drosophila. Three phenotypically identical mutations, cinnabar, scarlet, and cinnabar-2, are tested for allelism by making pairwise crosses between flies homozygous for different mutations.

20 Variation Among the Effects of Mutations Genes are identified by mutations that alter the phenotype in some conspicuous way. For instance, a mutation may change the color or shape of the eyes, alter a behavior, or cause sterility or even death.

21 Variation Among the Effects of Mutations Mutations affecting morphology are called visible mutations, those affecting reproduction sterile mutations, and those disrupting vital functions lethal mutations.

22 Variation among the effect of mutations A Y, the yellow-lethal mutation in mice: a dominant visible that is also a recessive lethal. A cross between carriers of this mutation produces yellow heterozygotes and gray-brown (agouti) homozygotes in a ratio of 2 : 1. The yellow homozygotes die as embryos.

23 Gene function to produce polypeptides The extensive variation revealed by mutations indicates that organisms contain many different genes and that these genes can exist in multiple allelic states. However, it does not tell us how genes actually affect the phenotype. What is it about a gene that enables it to influence a trait such as eye color, seed texture, or plant height? The early geneticists had no answer to this question.

24 Gene function to produce polypeptides

25 Why are some mutations dominant and others recessive?

26 Why are some mutations dominant and others recessive? - Recessive mutations occur when a gene loses its function : loss-of-function alleles - Dominant mutations occur when a gene acquires a new function : gain-of function alleles, neomorphic allele (new form)

27 Why are some mutations dominant and others recessive?

28 Why are some mutations dominant and others recessive?

29 Gene action : from genotype to phenotype -phenotypes depend on both environmental and genetic factors. Influence of the environment Environmental effects on the expression of human genes Penetrance and expressivity Gene interactions Epistasis Pleiotrophy

30 GENE ACTION: FROM GENOTYPE TO PHENOTYPE At the normal culturing temperature, 25 C, shibire flies are viable and fertile, but are extremely sensitive to a sudden shock. When a shibire culture is shaken, the flies temporarily paralyzed fall to the bottom of the culture. If a culture of shibire flies is placed at a slightly higher temperature, 29 C, all the flies fall to the bottom and die, even without a shock.

31 GENE ACTION: FROM GENOTYPE TO PHENOTYPE Phenylketonuria (PKU) is a recessive disorder of amino acid metabolism. Infants homozygous for the mutant allele accumulate toxic substances in their brains; though not lethal, these substances can impair mental ability by affecting the brain's development. However, infants who are fed low-phenylalanine diets usually mature without serious mental impairment.

32 Environmental effects on the expression of human genes - Pattern baldness Premature pattern baldness is due to an allele that is expressed differently in the two sexes. In males, both homozygotes and heterozygotes for this allele develop bald patches, whereas in females, only the homozygotes show a tendency to become bald, and this is usually limited to general thinning of the hair.

33 Penetrance - When individuals do not show a trait even though they have the appropriate genotype, the trait is said to exhibit incomplete penetrance The percentage of individuals that show a particular phenotype among those capable of showing it. 예 : polydactyly

34 Penetrance III-2: Incomplete penetrance can be a serious problem in pedigree analysis

35 GENE ACTION: FROM GENOTYPE TO PHENOTYPE Expressivity describes a trait not uniformly expressed in all offspring but all offspring show the trait. Thus, only the degree of expression differs among individuals.

36 Expressivity - Used if a trait is not manifested uniformly among the individuals that show it. Degree of expression of a trait controlled by a gene.

37 GENE ACTION: FROM GENOTYPE TO PHENOTYPE Some of the first evidence that a trait can be influenced by more than one gene was obtained by Bateson and Punnett

38 Gene interactions a. Rose, Wyandottes; b. pea, Brahmas; c. walnut, hybrid from cross between chickens with rose and pea combs; d. single, Leghorns.

39 Epistasis is an important genetic phenomenon involving two or more genes influencing a single trait. When an allele of one gene overrides the effects of the others, it is epistatic to the other genes. This situation arises in many areas of genetic analysis. -Many genes affect synthesis of eye pigments in Drosophila and flies homozygous for any null alleles have abnormal eye color. -cinnabar encodes a pigment transporter in flies so that flies synthesizing red pigment still have colorless eyes.

40 ` Epistasis - When two or more genes influence a trait, an allele of one of them may have an overriding effect on the phenotype - Interactions between products of nonallelic genes. White and purple flowers of the sweet pea.

41 Epistasis -Two flower color loci in the sweet pea, C and P, encode enzymes that synthesize anthocyanin in two sequential steps; pigment is not produced whenever the null alleles are homozygous. Crosses of F1 double heterozygotes yield 9:7 purple:white F2 plants. This is an example of sequential gene action with altered Mendelian ratios.

42 Epistasis -Two genes, each of which can act to produce the triangular shape, control triangular or ovoid seed capsules in the shepherd s purse. They both act at the same step in parallel so that ovoid capsules only occur in double recessive homozygotes yielding a 15:1 ratio when double heterozygotes are crossed.

43 the dominant allele of one gene is epistatic over the recessive allele of the other.

44 Epistasis

45 Epistasis

46 Epistasis

47 Pleiotrophy - Condition in which a single gene influences more than one trait. Phenyl ketonuria Singed bristle mutant in Drosophila

48 A single gene can also have pleiotropic or multiple effects on phenotype as in PKU in humans, altering skin and hair color besides mental impairment. Phenylketonuria: mental impairment, interfere with synthesis of melanin pigment, lightening the color of the hair.

49 Mendel's 7 traits were controlled by alleles acting discontinuously, e.g., tall or dwarf, yellow or green, etc. Many traits such as height, weight, and agricultural yield are complex and controlled by many genes so that they vary continuously within a population. Each gene contributes a small effect to the trait so Mendelian segregation is virtually impossible to demonstrate without the statistical methods developed by quantitative genetics.