Presentation on theme: "The Chromosomal Basis of Inheritance"— Presentation transcript:
1 The Chromosomal Basis of Inheritance Chapter 15The Chromosomal Basis of InheritanceWhat you learned alreadyChapter 13 : Meiosis and sexual life cyclesChapter 14 : Mendel and the gene idea
2 ☞Genes ( passengers) and chromosomes ( wagon) Overview: Locating Genes on Chromosomes☞Genes ( passengers) and chromosomes ( wagon)Mendel’s “hereditary factors” were genes, though this wasn’t known at the timeToday we can show that genes are located on chromosomesQ: How to visualize that?The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene Chromosomes: a physical basis for the principles of heredity (=Mendel’s laws of segregation and independent assortment)This chapter’s aim: Is to study the chromosomal basis for the transmission of genes from parents to offspring
3 Concept 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes Mitosis and meiosis were first described in the late 1800sThe chromosome theory of inheritance states:Mendelian genes have specific loci (positions) on chromosomesChromosomes undergo segregation and independent assortmentThe behavior of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment
4 Figure 15.2P GenerationYellow-round seeds (YYRR)Green-wrinkled seeds (yyrr)YryYRRryMeiosisFertilizationRYyrGametesAll F1 plants produce yellow-round seeds (YyRr).F1 GenerationRRyyrrYYMeiosisLAW OF SEGREGATION The two alleles for each gene separate during gamete formation.LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation.RrrRMetaphase IYyYy11RrrRAnaphase IYyYyFigure 15.2 The chromosomal basis of Mendel’s laws.RrrR22YyMetaphase IIYyYyYyYYyyGametesRRrrrrRR1/4YR1/4yr1/4Yr1/4yRF2 GenerationAn F1 F1 cross-fertilization3Fertilization recombines the R and r alleles at random.Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation.39: 3: 3: 1
5 All F1 plants produce yellow-round seeds (YyRr). Figure 15.2bAll F1 plants produce yellow-round seeds (YyRr).F1 GenerationRRyyrrYYLAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation.LAW OF SEGREGATION The two alleles for each gene separate during gamete formation.MeiosisRrrRMetaphase IYyYy11RrrRAnaphase IYyYyFigure 15.2 The chromosomal basis of Mendel’s laws.RrrRMetaphase II22YyYyYyYYyYyyGametesRRrrrrRR1/4YR1/4yr1/4Yr1/4yR
6 LAW OF INDEPENDENT ASSORTMENT Figure 15.2cLAW OF SEGREGATIONLAW OF INDEPENDENT ASSORTMENTF2 GenerationAn F1 F1 cross-fertilization3Fertilization recombines the R and r alleles at random.3Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation.9: 3: 3: 1Figure 15.2 The chromosomal basis of Mendel’s laws.
7 Summary for the chromosomal basis of Mendel’s laws Law of segregation:Two alleles for each gene segregate during gamete formation and end up in different gametes Each gamete gets only one of the two alleles In terms of chromosomes, this segregation corresponds to the distribution of homologous chromosomes to different gamete (R or r allele; Y or y allele)Law of independent assortment:Alleles of genes on nonhomologous chromosomes assort independently during gamete formation Each gamete gets one of four allele combinations (YR:Yr:yR:yr = 1:1:1:1) depending on the alternative arrangements of homologous chromosome pairs in metaphase I
8 Morgan’s Experimental Evidence for chromosomal theory: Scientific Inquiry Thomas Hunt Morgan (Embryologist at Columbia Univ. early in the 20th century)Provided the first solid evidence associating a specific gene with a specific chromosomeNamely, provided convincing evidence that chromosomes are the location of Mendel’s heritable factorsMorgan’s Choice of Experimental OrganismSeveral characteristics make fruit flies a convenient organism for genetic studies:They breed at a high rateA generation can be bred every two weeksThey have only four pairs of chromosomes
9 Morgan first observed and noted : Wild type, or normal, phenotypes that were common in the fly populationsTraits alternative to the wild type: Are called mutant phenotypesMorgan first invented a notation for symbolizing alleles in Drosophila (still widely used)The allele for white eyes in flies is symbolized by w (indicated as a mutant allele)A superscript + identifies the allele for the wild-type trait: w+ for the allele for red eyes
10 How to Correlate Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type)The F1 generation all had red eyesThe F2 generation showed the 3:1 red:white eye ratio, but only males had white eyesMorgan determined that the white-eyed mutant allele must be located on the X chromosomeMorgan’s finding supported the chromosome theory of inheritance
11 Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color traitWas the first solid evidence indicating that a specific gene is associated with a specific chromosomeFigure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have?
12 What will you examine here How to determine sex in an organism? 성염색체 연관 유전자의 유전현상의 특징Concept 15.2: Sex-linked genes exhibit unique patterns of inheritanceWhat will you examine hereWe consider the role of sex chromosome in heritanceFirst step: reviewing the chromosomal basis of sex determination in humans and some other animalsThe Chromosomal Basis of Sex (성결정과 염색체)How to determine sex in an organism?An organism’s sexIs an inherited phenotypic character determined by the presence or absence of certain chromosomes (sex chromosomes)
13 In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosomeOnly the ends of the Y chromosome have regions that are homologous with the X chromosomeThe SRY gene on the Y chromosome codes for the development of testes
14 (d) The haplo-diploid system Different systems of sex determinationAre found in other organisms22 +XXX76 +ZZZW16(Haploid)(Diploid)(b) The X–0 system(c) The Z–W system(d) The haplo-diploid systemIn grasshoppers, cockroaches, there is only one type of sex chromosome (the X)In birds, some fishes, and some insects, the sex chromosome present in the egg (not the sperm) determines the sex of offspring (Z and W)In most species of bees and ants, there are no sex chromosomes. Female develop from fertilized eggs and are thus diploid. Males develop from unfertilized eggs and haploid (no fathers)32Figure 15.6b–d
15 Inheritance of Sex-Linked Genes Key points to keep in mindThe sex chromosomes have genes for many characters unrelated to sexA gene located on either sex chromosome is called a sex-linked geneIn humans, sex-linked usually refers to a gene on the larger X chromosomeSex-linked trait by recessive allele on X chromosomeFemale: has two X chromosomesHomozygous recessive alleles : expression of phenotypeHeterozygous: no expression of phenotype (called carrier)Male: has only one X chromosomeYou don’t use the terms homozygous and heterozygous: use “hemizygous”Any male receiving the recessive allele from his mother will express the trait far more males than females have sex-linked recessive disorders (The freq. of sex-linked recessive disorders in male is higher than that in female)
16 What kinds of X-lined disorders are found? Some recessive alleles found on the X chromosome in humans cause certain types of disordersColor blindness:Duchenne muscular dystrophy : 1/3500 males born in US; progressive weakening of the muscles; the absence of a key muscle protein called dystrophinHemophilia: shows delayed blood clotting due to the absence of one or more of the proteins required for blood clotting; treated with intravenous injections of the missing protein
17 How do sex-lined recessive traits transmit to offspring? XAXa(a)A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.Figure 15.7a–c
18 The transmission of sex-linked recessive traits XaXA(b)If a carrier female mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.Figure 15.7a–c
19 The transmission of sex-linked recessive traits XaXa(c)If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.Figure 15.7a–c
20 X inactivation in Female Mammals In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic developmentThe inactive X condenses into a Barr bodyIf a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that characterMystery of the presence or absence of sweat glands in female skinIn humans, mosaicism can be observed in a recessive X-linked mutation that prevents the development of sweat glandsA woman who is heterozygous for this trait has patches of normal skin and patches of skin lacking sweat glands
21 Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosomeEach chromosome has hundreds or thousands of genesLocation of some genes on the same chromosome is expectedThe genes tend to be inherited together in genetic crosses: are said to be linked genesThe linked genes do not always follow Mendel’s law of independent assortment
22 How Linkage Affects Inheritance Morgan did other experiments with fruit flies to see how linkage affects inheritance of two charactersMorgan crossed flies that differed in traits of body color and wing size
23 However, nonparental phenotypes were also produced The production of a small number of offspring with nonparental phenotypes indicated that some mechanism occasionally breaks the linkage between genes on the same chromosomeUnderstanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parentFigure 15.UN01 In-text figure, p. 294
24 Genetic Recombination and Linkage What you learned in the Chapter 13Meiosis and random fertilization generate genetic variation among offspring of sexually reproducing organismsThe genetic findings of Mendel and Morgan relate to the chromosomal basis of recombinationWhat will you examine nextWhat is the chromosomal basis of recombination in relation to the genetic findings of Mendel and Morgan?
25 Recombination of Unlinked Genes: Independent Assortment of Chromosomes Mendel observed that combinations of traits in some offspring differ from either parentOffspring with a phenotype matching one of the parental phenotypes are called parental typesOffspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinantsA 50% frequency of recombination is observed for any two genes on different chromosomes
26 Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observedHe proposed that some process must occasionally break the physical connection between genes on the same chromosomeThat mechanism was the crossing over of homologous chromosomes
27 Figure 15.10Testcross parentsReplication of chromosomesGray body, normal wings (F1 dihybrid)Black body, vestigial wings (double mutant)Meiosis IMeiosis IIMeiosis I and IIRecombinant chromosomesEggsb vgb vgb vgb vgb vgb vgbvgTestcross offspring965 Wild type (gray-normal)944 Black- vestigial206 Gray- vestigial185 Black- normalSpermParental-type offspringRecombinant offspringRecombination frequency391 recombinants 2,300 total offspring 17%Chromosomal basis for recombination of linked genes: Linked genes exhibit RF less than 50%Figure Chromosomal basis for recombination of linked genes.
28 Gray body, normal wings (F1 dihybrid) Figure 15.10aTestcross parentsGray body, normal wings (F1 dihybrid)Black body, vestigial wings (double mutant)b vgb vgb vgb vgReplication of chromosomesReplication of chromosomesb vgb vgb vgb vgb vgb vgMeiosis I: Crossingover between b and vgloci produces new allelecombinations.b vgb vgb vgMeiosis I and II:Even if crossing overoccurs, no new allelecombinations areproduced.b vgMeiosis II: Segregationof chromatids producesrecombinant gameteswith the new allelecombinations.Figure Chromosomal basis for recombination of linked genes.b vgb vgRecombinant chromosomesbvgb vgb vgb vgb vgEggsSperm
29 Recombinant chromosomes Figure 15.10bRecombinant chromosomesbvgb vgb vgb vgEggsTestcross offspring965 Wild type (gray-normal)944 Black- vestigial206 Gray- vestigial185 Black- normalb vgb vgb vgb vgb vgb vgb vgb vgb vgFigure Chromosomal basis for recombination of linked genes.SpermParental-type offspringRecombinant offspringRecombination frequency391 recombinants 2,300 total offspring 17%RF: the percentage of recombinants in the total offspring
30 Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosomeSturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequencyA linkage map is a genetic map of a chromosome based on recombination frequenciesDistances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequencyMap units indicate relative distance and order, not precise locations of genes
31 How to construct a linkage map ExampleConsider three genes: the body-color (b), wing-size (vg), and cinnabar eyes (cn) [brighter red than wt eye color]The observed recombination frequencies between three Drosophila gene pairs : b–cn 9%, cn–vg 9.5%, and b–vg 17%Make a linear order : cn is positioned about halfway between the other two genes:ChromosomeRecombination frequencies9%9.5%17%bcnvgRESULTSb, black body colorvg, vestigial wingcn, cinnabar eyes1st cross-over2nd COFigure 15.11
32 How to construct a linkage map (continued) ExampleInquiry: The b–vg recombination frequency (17%) is slightly less than the sum (18.5%) of the b–cn and cn–vg frequencies. Why?Because double crossovers are fairly likely to occur between b and vg in matings tracking these two genes.A second crossover would “cancel out” the effect of the first crossover and thus reduce the observed b–vg RF.
33 Canceling out of the effect of the 1st crossover by 2nd cross-over
34 Genes that are far apart on the same chromosome can have a recombination frequency near 50% Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomesSturtevant used recombination frequencies to make linkage maps of fruit fly genesUsing methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomesCytogenetic maps indicate the positions of genes with respect to chromosomal features
35 Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disordersPlants tolerate such genetic changes better than animals do
36 Abnormal Chromosome Number In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosisAs a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy
37 The consequences of nondisjunction after fertilization? AneuploidyResults from the fertilization of aberrant gametes (nondisjunction occurred) with a normal oneIs a condition in which offspring have an abnormal number of a particular chromosomePolyploidy is a condition in which an organism has more than two complete sets of chromosomesTriploidy (3n) is three sets of chromosomesTetraploidy (4n) is four sets of chromosomesPolyploidy is common in plants, but not animalsPolyploids are more normal in appearance than aneuploidsChromosome number of haploid (gamete): nChromosome number of normal zygote: 2nIf a zygote is trisomic (2n+1 chromosomes)It has three copies of a particular chromosomeIf a zygote is monosomic (2n-1 chromosomes)It has only one copy of a particular chromosome
38 Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structureDeletion removes a chromosomal segmentDuplication repeats a segmentInversion reverses orientation of a segment within a chromosomeTranslocation moves a segment from one chromosome to another
39 Human Disorders Due to Chromosomal Alterations Alterations of chromosome number and structure are associated with some serious disordersSome types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyondThese surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidyDown Syndrome (Trisomy 21)Down syndrome is an aneuploid condition that results from three copies of chromosome 21It affects about one out of every 700 children born in the United StatesThe frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained
40 Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditionsKlinefelter syndrome is the result of an extra chromosome in a male, producing XXY individualsMonosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans
41 Disorders Caused by Structurally Altered Chromosomes The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhoodCertain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes
42 Concept 15.5: Some inheritance patterns are exceptions to the standard chromosome theory There are two normal exceptions to Mendelian geneticsOne exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleusIn both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritanceGenomic ImprintingFor a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traitsSuch variation in phenotype is called genomic imprinting (Monoallelic expression)Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production
43 Genomic imprintingInvolves the silencing of certain genes that are “stamped” with an imprint during gamete productionA zygote expresses only one allele of an imprinted gene (either from the mother or the father) The imprints are transmitted to all the body cells during developmentA gene imprinted for maternal allele expression is always imprinted for maternal allele expression, generation to generation
44 Genomic imprinting of the mouse Igf2 gene. Figure 15.17aGenomic imprinting of the mouse Igf2 gene.Figure Genomic imprinting of the mouse Igf2 gene.
45 Inheritance of Organelle Genes Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasmMitochondria, chloroplasts, and other plant plastids carry small circular DNA moleculesExtranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the eggThe first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant (see next slide)