Chapter 15: The Chromosomal Basis of Inheritance PDF

LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 15 The Chromosomal Basis of Inheritance...

LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 15 The Chromosomal Basis of Inheritance Lectures by Erin Barley Kathleen Fitzpatrick © 2011 Pearson Education, Inc. Overview: Locating Genes Along Chromosomes Mendel’s “hereditary factors” were genes Today we can show that genes are located on chromosomes The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene © 2011 Pearson Education, Inc. Figure 15.1 Concept 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes Mitosis and meiosis were first described in the late 1800s The chromosome theory of inheritance states: – Mendelian genes have specific loci (positions) on chromosomes – Chromosomes undergo segregation and independent assortment The behavior of chromosomes during meiosis can account for Mendel’s laws of segregation and independent assortment © 2011 Pearson Education, Inc. Figure 15.2a P Generation Yellow-round Green-wrinkled seeds (YYRR) seeds (yyrr) Y y  r R R r Y y Meiosis Fertilization R Y y r Gametes Figure 15.2b All F1 plants produce yellow-round seeds (YyRr). F1 Generation R R y y r r Y Y LAW OF INDEPENDENT LAW OF SEGREGATION Meiosis ASSORTMENT Alleles of The two alleles for each R r r R genes on nonhomologous gene separate during chromosomes assort gamete formation. Metaphase I independently during gamete Y y Y y formation. 1 1 R r r R Anaphase I Y y Y y R r r R Metaphase 2 II 2 Y y Y y Y y Y Y y Y y y Gametes R R r r r r R R /4 YR 1 /4 yr 1 1 /4 Yr 1 /4 yR Figure 15.2c LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT F2 Generation An F1  F1 cross-fertilization 3 Fertilization 3 Fertilization results recombines the in the 9:3:3:1 R and r alleles 9 :3 :3 :1 phenotypic ratio in at random. the F2 generation. Morgan’s Experimental Evidence: Scientific Inquiry The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors © 2011 Pearson Education, Inc. Morgan’s Choice of Experimental Organism Several characteristics make fruit flies a convenient organism for genetic studies – They produce many offspring – A generation can be bred every two weeks – They have only four pairs of chromosomes © 2011 Pearson Education, Inc.  Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes © 2011 Pearson Education, Inc. Figure 15.3 Correlating 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 eyes – The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes Morgan determined that the white-eyed mutant allele must be located on the X chromosome Morgan’s finding supported the chromosome theory of inheritance © 2011 Pearson Education, Inc. Figure 15.4a EXPERIMENT P Generation F1 All offspring Generation had red eyes. RESULTS F2 Generation Figure 15.4b CONCLUSION P w w X X Generation X Y w w Sperm Eggs F1 w w w  Generation w w Sperm Eggs w w w F2 Generation w w w w w  Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color trait – Was the first solid evidence indicating that a specific gene is associated with a specific chromosome – Genes on sex chromosomes exhibit unique inheritance patterns – Linked genes: genes that are located on the same chromosome and tend to be inherited together. linked genes do not assort independently because they are on the same chromosome. A dihybrid cross following two linked genes will Not produce an F2 phenotypic ratio of 9:3:3:1. Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance In humans and some other animals, there is a chromosomal basis of sex determination © 2011 Pearson Education, Inc.  The Chromosomal Basis of Sex In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome © 2011 Pearson Education, Inc. Figure 15.5 X Y  Females are XX, and males are XY Each ovum contains an X chromosome, while a sperm may contain either an X or a Y chromosome Other animals have different methods of sex determination © 2011 Pearson Education, Inc. Figure 15.6a 44  44  Parents XY XX 22  22  22  or X X Y Sperm Egg 44  44  XX or XY Zygotes (offspring) (a) The X-Y system  The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features 78 genes on Y that code for 25 proteins, ½ are expressed in the testes A gene that is located on either sex chromosome is called a sex-linked gene Genes on the Y chromosome are called Y-linked genes; there are few of these e.g hypertrichosis of the pinna (excessively hairy ears) Genes on the X chromosome are called X-linked genes © 2011 Pearson Education, Inc. Figure 15.6b 22  22  XX X Sex is determined by whether the sperm (b) The X-0 system cell contains an X chr or no sex chr 76  76  ZW ZZ (c) The Z-W system The sex chrs in the egg determine sex 32 16 (Diploid) (Haploid) (d) The haplo-diploid system There are no sex chrs Females develop from fertilized eggs and males develop from unfertilized egg (have no fathers) Inheritance of X-Linked Genes X chromosome have genes for many characters unrelated to sex, whereas the Y chromosome mainly encodes genes related to sex determination © 2011 Pearson Education, Inc.  X-linked genes follow specific patterns of inheritance For a recessive X-linked trait to be expressed – A female needs two copies of the allele (homozygous) – A male needs only one copy of the allele (hemizygous) X-linked recessive disorders are much more common in males than in females © 2011 Pearson Education, Inc. Figure 15.7 The transmission of X-linked recessive traits Color-blindness XNXN XnY XNXn XNY XNXn X nY Sperm Xn Y Sperm XN Y Sperm Xn Y Eggs XN XNXn XNY Eggs XN XNXN XNY Eggs XN XNXn XNY XN XNXn XNY Xn X NX n X n Y Xn XnXn Xn Y (a) (b) (c)  Some disorders caused by recessive alleles on the X chromosome in humans – Color blindness (mostly X-linked) – Duchenne muscular dystrophy – Hemophilia © 2011 Pearson Education, Inc. X Inactivation in Female Mammals In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development The inactive X condenses into a Barr body If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character © 2011 Pearson Education, Inc. Figure 15.8 X chromosomes Allele for orange fur Early embryo: Allele for black fur Cell division and X chromosome Two cell inactivation populations in adult cat: Active X Inactive X Active X Black fur Orange fur If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character Tortoiseshell cat Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome Each chromosome has hundreds or thousands of genes (except the Y chromosome) Genes located on the same chromosome that tend to be inherited together are called linked genes © 2011 Pearson Education, Inc. How Linkage Affects Inheritance Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters Morgan crossed flies that differed in traits of body color and wing size © 2011 Pearson Education, Inc. Figure 15.9-4 EXPERIMENT P Generation (homozygous) Double mutant Wild type (black body, (gray body, normal wings) vestigial wings) b b vg vg b b vg vg F1 dihybrid Double mutant TESTCROSS (wild type) b b vg vg b b vg vg Testcross offspring Eggs b vg b vg b vg b vg Wild type Black- Gray- Black- (gray-normal) vestigial vestigial normal b vg Sperm b b vg vg b b vg vg b b vg vg b b vg vg PREDICTED RATIOS If genes are located on different chromosomes: 1 : 1 : 1 : 1 If genes are located on the same chromosome and parental alleles are always inherited together: 1 : 1 : 0 : 0 RESULTS 965 : 944 : 206 : 185  Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes) He noted that these genes do not assort independently, and reasoned that they were on the same chromosome © 2011 Pearson Education, Inc. Figure 15.UN01 b+ vg+ b vg F1 dihybrid female and homozygous recessive male b vg b vg in testcross b+ vg+ b vg Most offspring or b vg b vg  However, nonparental phenotypes were also produced Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent © 2011 Pearson Education, Inc. Genetic Recombination and Linkage The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination © 2011 Pearson Education, Inc. Recombination of Unlinked Genes: Independent Assortment of Chromosomes Mendel observed that combinations of traits in some offspring differ from either parent Offspring with a phenotype matching one of the parental phenotypes are called parental types Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants A 50% frequency of recombination is observed for any two genes on different chromosomes © 2011 Pearson Education, Inc. Figure 15.UN02 Gametes from yellow-round dihybrid parent (YyRr) YR yr Yr yR Gametes from green- wrinkled homozygous yr recessive parent (yyrr) YyRr yyrr Yyrr yyRr Parental- Recombinant type offspring offspring Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed He proposed that some process must occasionally break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes © 2011 Pearson Education, Inc. Figure 15.10a Testcross Gray body, normal wings Black body, vestigial wings parents (F1 dihybrid) (double mutant) b vg b vg b vg b vg Replication Replication of chromosomes of chromosomes b vg b vg b vg b vg b vg b vg b vg b vg Meiosis I b vg Meiosis I and II b vg b vg b vg Meiosis II Recombinant chromosomes bvg b vg b vg b vg b vg Eggs Sperm Figure 15.10b Recombinant chromosomes bvg b vg b vg b vg Eggs Testcross 965 944 206 185 offspring Wild type Black- Gray- Black- (gray-normal) vestigial vestigial normal b vg b vg b vg b vg b vg b vg b vg b vg b vg Sperm Parental-type offspring Recombinant offspring Recombination 391 recombinants  100  17% frequency  2,300 total offspring New Combinations of Alleles: Variation for Normal Selection Recombinant chromosomes bring alleles together in new combinations in gametes Random fertilization increases even further the number of variant combinations that can be produced This abundance of genetic variation is the raw material upon which natural selection works © 2011 Pearson Education, Inc. 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 chromosome Sturtevant 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 frequency © 2011 Pearson Education, Inc.  A linkage map is a genetic map of a chromosome based on recombination frequencies Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency Map units indicate relative distance and order, not precise locations of genes © 2011 Pearson Education, Inc. Figure 15.11 RESULTS Recombination frequencies 9% 9.5% Chromosome 17% b cn vg  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 chromosomes © 2011 Pearson Education, Inc.  Sturtevant used recombination frequencies to make linkage maps of fruit fly genes Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes Cytogenetic maps indicate the positions of genes with respect to chromosomal features © 2011 Pearson Education, Inc. Figure 15.12 Mutant phenotypes Short Black Cinnabar Vestigial Brown aristae body eyes wings eyes 0 48.5 57.5 67.0 104.5 Long aristae Gray Red Normal Red (appendages body eyes wings eyes on head) Wild-type phenotypes 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 disorders Plants tolerate such genetic changes better than animals do © 2011 Pearson Education, Inc. Abnormal Chromosome Number In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy © 2011 Pearson Education, Inc. Figure 15.13-3 Meiosis I Nondisjunction Meiosis II Non- disjunction Gametes n1 n1 n1 n1 n1 n1 n n Number of chromosomes (a) Nondisjunction of homo- (b) Nondisjunction of sister logous chromosomes in chromatids in meiosis II meiosis I  Aneuploidy results from the fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome © 2011 Pearson Education, Inc.  A monosomic zygote has only one copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome © 2011 Pearson Education, Inc.  Polyploidy is a condition in which an organism has more than two complete sets of chromosomes – Triploidy (3n) is three sets of chromosomes – Tetraploidy (4n) is four sets of chromosomes Polyploidy is common in plants, but not animals Polyploids are more normal in appearance than aneuploids © 2011 Pearson Education, Inc. Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure – Deletion removes a chromosomal segment – Duplication repeats a segment – Inversion reverses orientation of a segment within a chromosome – Translocation moves a segment from one chromosome to another © 2011 Pearson Education, Inc. Figure 15.14a (a) Deletion A B C D E F G H A deletion removes a chromosomal segment. A B C E F G H (b) Duplication A B C D E F G H A duplication repeats a segment. A B C B C D E F G H Figure 15.14b (c) Inversion A B C D E F G H An inversion reverses a segment within a chromosome. A D C B E F G H (d) Translocation A B C D E F G H M N O P Q R A translocation moves a segment from one chromosome to a nonhomologous chromosome. M N O C D E F G H A B P Q R Human Disorders Due to Chromosomal Alterations Alterations of chromosome number and structure are associated with some serious disorders Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy © 2011 Pearson Education, Inc. Down Syndrome (Trisomy 21) Down syndrome is an aneuploid condition that results from three copies of chromosome 21 It affects about one out of every 700 children born in the United States The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained flattened face and nose, a short neck, a small mouth sometimes with a large, protruding tongue, small ears, upward slanting eyes that may have small skin folds at the inner corner white spots (Brushfield spots) may be present on the colored part of the eye (iris); the hands are short and broad with short fingers, and with a single crease in the palm; poor muscle tone and loose ligaments are also common; and development and growth is usually delayed and often average height and developmental milestones are not reached. © 2011 Pearson Education, Inc. Figure 15.15a  Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditions Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals Taller than average, with long arms and legs Small testes, mostly sterile, low testosterone levels, Gynecomastia in 1/3 of patients can be reduced by mastectomy, sparse body hair, reduced muscle mass, predisposition to learning disabilities and reduction in verbal IQ (although intelligence is normal) Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans 45, X, female, short stature, sexual infantilism and ovarian dysgenesis, major and minor malformations Triangle-shaped face, posteriorly rotated ears, broad webbed neck, broad shield-like chest, lymphedema of hand and feet at birth, congenital heart defects, structural kidney defects, normal intelligence © 2011 Pearson Education, Inc. Disorders Caused by Structurally Altered Chromosomes The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes © 2011 Pearson Education, Inc. Figure 15.16 Normal chromosome 9 Normal chromosome 22 Reciprocal translocation Translocated chromosome 9 Translocated chromosome 22 (Philadelphia chromosome) Concept 15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance There are two normal exceptions to Mendelian genetics One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance © 2011 Pearson Education, Inc. Genomic Imprinting For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits Such variation in phenotype is called genomic imprinting Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production © 2011 Pearson Education, Inc. Figure 15.17a Normal Igf2 allele is expressed. Paternal chromosome Maternal chromosome Normal-sized mouse Normal Igf2 allele (wild type) is not expressed. (a) Homozygote Figure 15.17b Mutant Igf2 allele Mutant Igf2 allele inherited from mother inherited from father Normal-sized mouse (wild type) Dwarf mouse (mutant) Normal Igf2 allele Mutant Igf2 allele is expressed. is expressed. Mutant Igf2 allele Normal Igf2 allele is not expressed. is not expressed. (b) Heterozygotes Mating between W.T mice and those homozygous for the recessive Igf2 allele produce heterozygous offspring. The dwarf (mutant) phenotype is seen only when the father contributed the mutant allele because the maternal allele is not expressed  It appears that imprinting is the result of the methylation (addition of –CH3) of cytosine nucleotides Genomic imprinting is thought to affect only a small fraction of mammalian genes Most imprinted genes are critical for embryonic development © 2011 Pearson Education, Inc. Inheritance of Organelle Genes Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant by Karl Correns Coloration of the offspring was determined only by the maternal parent and not by the paternal parent and is due to mutations in plastid genes © 2011 Pearson Education, Inc. Figure 15.18  Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems – For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy © 2011 Pearson Education, Inc. END