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

Figure 15.1 Figure 15.1 Where are Mendel’s hereditary factors located in the cell?

CONCEPT 15.1: MENDELIAN INHERITANCE HAS ITS PHYSICAL BASIS IN THE BEHAVIOR OF CHROMOSOMES

Mendel and Meiosis Figure 15.2 The chromosomal basis of Mendel’s laws. P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) Y r y  R Y R r y Meiosis Fertilization R Y y r Gametes All F1 plants produce yellow-round seeds (YyRr). F1 Generation R R y y r r Y Y Meiosis LAW 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. R r r R Metaphase I Y y Y y 1 1 R r r R Anaphase I Y y Y y R r r R Figure 15.2 The chromosomal basis of Mendel’s laws. 2 2 Y y Metaphase II Y y y Y Y y Y Y y y Gametes R R r r r r R R 1/4 YR 1/4 yr 1/4 Yr 1/4 yR F2 Generation An F1  F1 cross-fertilization 3 Fertilization recombines the R and r alleles at random. 3 Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9 : 3 : 3 : 1

Mendel and Meiosis P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) Y y  r R Y R r y Meiosis Fertilization R Y y r Gametes Figure 15.2 The chromosomal basis of Mendel’s laws.

F1 Generation All F1 plants produce yellow-round seeds (YyRr). Figure 15.2b All F1 plants produce yellow-round seeds (YyRr). F1 Generation R R y y r r Y Y LAW 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. Meiosis R r r R Metaphase I Y y Y y 1 1 R r r R Anaphase I Y y Y y Figure 15.2 The chromosomal basis of Mendel’s laws. R r r R Metaphase II 2 2 Y y Y y Y y Y Y y Y y y Gametes R R r r r r R R 1/4 YR 1/4 yr 1/4 Yr 1/4 yR

Mendel and Meiosis LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT F2 Generation An F1  F1 cross-fertilization 3 Fertilization recombines the R and r alleles at random. 3 Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9 : 3 : 3 : 1 Figure 15.2 The chromosomal basis of Mendel’s laws.

Morgan’s Experimental Evidence for Mendel 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

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

Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes

Figure 15.4 EXPERIMENT P Generation The F1 generation all had red eyes The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes F1 Generation All offspring had red eyes. RESULTS F2 Generation CONCLUSION P Generation w w X X X Y w w Sperm Eggs F1 Generation w w Figure 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? w Morgan determined that the white-eyed mutant allele must be located on the X chromosome w w Sperm Eggs w w F2 Generation w w w w w w

P Generation F1 Generation F2 Generation EXPERIMENT P Generation F1 Generation All offspring had red eyes. RESULTS Figure 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? F2 Generation

P Generation F1 Generation F2 Generation CONCLUSION P Generation w w X X X Y w w Sperm Eggs F1 Generation w w w w w Sperm Figure 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? Eggs w w F2 Generation w w w w w w

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 CONCEPT 15.2: SEX-LINKED GENES EXHIBIT UNIQUE PATTERNS OF INHERITANCE

The Chromosomal Basis of Sex Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome The SRY gene on the Y codes for a protein that directs the development of male anatomical features X Y

Sex Determination Systems 44  XY Parents 44  XX Sex Determination Systems 22  X 22  Y 22  X or Sperm Egg 44  XX or 44  XY Human males are XY Human females are XX Other organisms use different systems! Zygotes (offspring) (a) The X-Y system 22  XX 22  X (b) The X-0 system 76  ZW 76  ZZ (c) The Z-W system 32 (Diploid) 16 (Haploid) (d) The haplo-diploid system

44  XY 44  XX Parents 22  X 22  X 22  Y or Sperm Egg 44  XX Figure 15.6a 44  XY 44  XX Parents 22  X 22  X 22  Y or Sperm Egg 44  XX 44  XY or Zygotes (offspring) (a) The X-Y system Figure 15.6 Some chromosomal systems of sex determination. 22  XX 22  X (b) The X-0 system

76  ZW 76  ZZ 32 (Diploid) 16 (Haploid) Figure 15.6b 76  ZW 76  ZZ (c) The Z-W system 32 (Diploid) 16 (Haploid) Figure 15.6 Some chromosomal systems of sex determination. (d) The haplo-diploid system

Sex-Linkage A gene that is located on either sex chromosome is called a sex-linked gene Genes on the Y = Y-linked genes; there are few of these Genes on the X = X-linked genes

X-linked Inheritance X chromosomes code for many genes not related to sex Some disorders caused by recessive alleles on the X chromosome in humans Color blindness (mostly X-linked) Duchenne muscular dystrophy Hemophilia

Transmitting X-linked genes: Colorblindness XNXN XnY XNXn XNY XNXn XnY 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 XNXn XnY Xn XnXn XnY (a) (b) (c) Figure 15.7 The transmission of X-linked recessive traits. 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

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

Female Mosaics: X Inactivation X chromosomes Allele for orange fur Early embryo: Allele for black fur Cell division and X chromosome inactivation Two cell populations in adult cat: Active X Inactive X Active X Black fur Orange fur Figure 15.8 X inactivation and the tortoiseshell cat.

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 Concept 15.3: Linked genes tend to be inherited together Because of Location

Gene Linkage Linked genes assort together

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 Double mutant (black body, vestigial wings) Wild type (gray body, normal wings)

P Generation (homozygous) Double mutant (black body, vestigial wings) Figure 15.9-1 EXPERIMENT P Generation (homozygous) Double mutant (black body, vestigial wings) Wild type (gray body, normal wings) b b vg vg b b vg vg Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?

P Generation (homozygous) Double mutant (black body, vestigial wings) Figure 15.9-2 EXPERIMENT P Generation (homozygous) Double mutant (black body, vestigial wings) Wild type (gray body, normal wings) b b vg vg b b vg vg F1 dihybrid (wild type) Double mutant TESTCROSS b b vg vg b b vg vg Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?

Wild type (gray-normal) Figure 15.9-3 EXPERIMENT P Generation (homozygous) Double mutant (black body, vestigial wings) Wild type (gray body, normal wings) b b vg vg b b vg vg F1 dihybrid (wild type) Double mutant TESTCROSS b b vg vg b b vg vg Testcross offspring Eggs b vg b vg b vg b vg Wild type (gray-normal) Black- vestigial Gray- vestigial Black- normal b vg Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters? Sperm b b vg vg b b vg vg b b vg vg b b vg vg

Wild type (gray-normal) Figure 15.9-4 EXPERIMENT P Generation (homozygous) Double mutant (black body, vestigial wings) Wild type (gray body, normal wings) b b vg vg b b vg vg F1 dihybrid (wild type) Double mutant TESTCROSS b b vg vg b b vg vg Testcross offspring Eggs b vg b vg b vg b vg Wild type (gray-normal) Black- vestigial Gray- vestigial Black- normal b vg Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters? 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 : : RESULTS 965 : 944 : 206 : 185

b+ vg+ b vg F1 dihybrid female and homozygous recessive male in testcross b vg b vg b+ vg+ b vg Most offspring or b vg b vg Figure 15.UN01 In-text figure, p. 294 Morgan found body color and wing size are usually inherited together in specific combinations (parental phenotypes)

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

Genetic Recombination and Linkage Offspring with a phenotype matching one of the parental phenotypes are called parental types Offspring with nonparental phenotypes are called recombinant types, or recombinants A 50% frequency of recombination is observed for any two genes on different chromosomes

Parental vs. Recombinant Phenotypes Gametes from yellow-round dihybrid parent (YyRr) YR yr Yr yR Gametes from green- wrinkled homozygous recessive parent (yyrr) yr YyRr yyrr Yyrr yyRr Figure 15.UN02 In-text figure, p. 294 Parental- type offspring Recombinant 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 Some process must occasionally break the physical connection between genes on the same chromosome

Crossing Over and Recombination Testcross parents Gray body, normal wings (F1 dihybrid) Black body, vestigial wings (double mutant) Crossing Over and Recombination b vg b vg b vg b vg Replication of chromosomes Replication 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 Recombinant chromosomes bring alleles together in new combinations in gametes Genetic variation drives evolution! b vg b vg b vg Meiosis II Recombinant chromosomes bvg b vg b vg b vg Eggs Figure 15.10 Chromosomal basis for recombination of linked genes. Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- 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 frequency 391 recombinants 2,300 total offspring   100  17%

Recombination frequencies Mapping Distance Between Genes Using Recombination Data Recombination frequencies 1 map unit = 1% recombination frequency 9% 9.5% Chromosome 17% b cn vg A linkage map is a genetic map of a chromosome based on recombination frequencies The farther apart two genes are, the higher the probability crossover will occur and therefore the higher the recombination frequency Distances between genes can be expressed as map units. Figure 15.11 Research Method: Constructing a Linkage Map

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

Genetic Linkage Map: Cytogenic Mapping Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes 48.5 57.5 67.0 104.5 Figure 15.12 A partial genetic (linkage) map of a Drosophila chromosome. Long aristae (appendages on head) Gray body Red eyes Normal wings Red eyes Wild-type phenotypes

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 Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders

Chromosomal Changes and Disorders Abnormal Chromosome Number Alteration of Chromosome Structure

Abnormal Chromosome Number Meiosis I Nondisjunction In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis Figure 15.13 Meiotic nondisjunction.

Abnormal Chromosome Number Meiosis I Nondisjunction Meiosis II Non- disjunction As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy Figure 15.13 Meiotic nondisjunction.

Abnormal Chromosome Number Meiosis I Nondisjunction Meiosis II Non- disjunction Gametes Figure 15.13 Meiotic nondisjunction. n  1 n  1 n  1 n  1 n  1 n  1 n n Number of chromosomes Nondisjunction of homo- logous chromosomes in meiosis I (a) Nondisjunction of sister chromatids in meiosis II (b)

Aneuploidy The fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome

A monosomic zygote has only one copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome

Polyploidy: More than 2 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 Hexaploidy (6n) Triploidy (3n) Octoploidy (8n)

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

Alterations of Chromosome Structure (a) Deletion A C D E F G H B A deletion removes a chromosomal segment. A B C E F G H (b) Duplication A B C D E F G H Figure 15.14 Alterations of chromosome structure. A duplication repeats a segment. A B C D E F G H

Alterations of Chromosome Structure (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 Figure 15.14 Alterations of chromosome structure. A translocation moves a segment from one chromosome to a nonhomologous chromosome. G M N O C H F E D A B P Q R

Human Disorders Due to Chromosomal Alterations Most mammalian aneuploidy are lethal but some survive to birth and beyond These surviving individuals have a set of symptoms, or syndrome.

Down Syndrome (Trisomy 21) Down syndrome is an aneuploid condition that results from three copies of chromosome 21 It affects about 1in 700 children born in the US The frequency of Down syndrome increases with the age of the mother

Aneuploidy of Sex Chromosomes Syndrome Genotype Occurrence Symptoms Klinefelter Syndrome XXY 1/500 ~ 1/1000 Underdeveloped testes Male is sterile Some secondary female characteristics XYY Syndrome XYY 1/1000 Normal sexual development Taller than average Increased aggression Turner Syndrome (Monosomy X) XO 1/2500 Only viable monosomy in humans Sex organs do not develop; sterile Trisomy X XXX Learning disabled Fertile Slightly taller

Turner’s Syndrome Klinefelter Syndrome

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

CML: Chronic Myelogenous Leukemia Normal chromosome 9 CML caused by translocations of chromosomes Normal chromosome 22 Reciprocal translocation Figure 15.16 Translocation associated with chronic myelogenous leukemia (CML). 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

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

Normal Igf2 allele is expressed. Figure 15.17 Normal Igf2 allele is expressed. Paternal chromosome Maternal chromosome Normal-sized mouse (wild type) Normal Igf2 allele is not expressed. (a) Homozygote Mutant Igf2 allele inherited from mother Mutant Igf2 allele inherited from father Normal-sized mouse (wild type) Dwarf mouse (mutant) Figure 15.17 Genomic imprinting of the mouse Igf2 gene. Normal Igf2 allele is expressed. Mutant Igf2 allele is expressed. Mutant Igf2 allele is not expressed. Normal Igf2 allele is not expressed. (b) Heterozygotes

It appears that imprinting is the result of the methylation (addition of —CH3) of cysteine nucleotides Genomic imprinting is thought to affect only a small fraction of mammalian genes Most imprinted genes are critical for embryonic development

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

Figure 15.18 Figure 15.18 Variegated leaves from English holly (Ilex aquifolium).

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

Sperm Egg C c B b D A d E a P generation gametes e F f Figure 15.UN03 Sperm Egg C c B b D A d E a P generation gametes e F f The alleles of unlinked genes are either on separate chromosomes (such as d and e) or so far apart on the same chromosome (c and f) that they assort independently. This F1 cell has 2n  6 chromo- somes and is heterozygous for all six genes shown (AaBbCcDdEeFf). Red  maternal; blue  paternal. D e C B d Figure 15.UN03 In-text figure, p. 294 A Genes on the same chromo- some whose alleles are so close together that they do not assort independently (such as a, b, and c) are said to be genetically linked. Each chromosome has hundreds or thousands of genes. Four (A, B, C, F) are shown on this one. E F f a c b

Figure 15.UN04 Figure 15.UN04 In-text figure, p. 294

Figure 15.UN05 Figure 15.UN05 In-text figure, p. 294

Figure 15.UN06 Figure 15.UN06 In-text figure, p. 294