The Chromosomal Basis of Inheritance 12 The Chromosomal Basis of Inheritance

Where are Mendel’s hereditary factors located in a cell? Figure 12.1 Figure 12.1 Where are Mendel's hereditary factors located in the cell? 2

Many biologists remained skeptical about Mendel’s laws of segregation and independent assortment until there was evidence that these principles had a physical basis in chromosomal behavior. Late 1800s: microscopy allowed parallels to be seen

Chromosomal Theory of Inheritance: Mendelian genes have specific loci along chromosomes It is the chromosomes that undergo segregation and independent assortment

P Generation Yellow-round Green-wrinkled seeds (YYRR) seeds (yyrr) Figure 12.2a P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) Y y r R R r Y y Meiosis Figure 12.2a The chromosomal basis of Mendel’s laws (part 1) Fertilization R Y y r Gametes 5

    All F1 plants produce yellow-round seeds (YyRr). F1 Generation Figure 12.2b All F1 plants produce yellow-round seeds (YyRr). F1 Generation R R y y r r Y Y Meiosis LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently. LAW OF SEGREGATION The two alleles for each gene separate. R r r R Metaphase I Y y Y y 1 1 R r r R Anaphase I Y y Y y Metaphase II R r r R Figure 12.2b The chromosomal basis of Mendel’s laws (part 2) 2 2 Y y Y y y Y Y Y Y y y y R R r r r r R R 1 4  YR 1 4  yr 1 4  Yr 1 4  yR 6

An F1  F1 cross-fertilization 3 Fertilization results in the 9:3:3:1 Figure 12.2c LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT F2 Generation 3 Fertilization recombines the R and r alleles at random. An F1  F1 cross-fertilization 3 Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9 : 3 : 3 : 1 Figure 12.2c The chromosomal basis of Mendel’s laws (part 3) 7

Thomas Hunt Morgan Provided first solid evidence associating a specific gene with a specific chromosome Worked with fruit flies

Thomas Hunt Morgan Used reciprocal crosses - 2 crosses where the trait of each sex is reversed Example - 1- White eyed male X Red eyed female 2- White eyed female X Red eyed male Red: wild type (most common) w+ White: mutant type w

White-eyed males show up in F2 Thomas Morgan X X 1/2 Y Y recessive male all red- eyed F1 offspring 1/2 1/4 X X 1/4 1/4 X X 1/2 1/4 X X 1/2 gametes White-eyed males show up in F2 generation Fig. 12-9, p.193

Morgan’s cross showed all red eyes (w+) for the F1 generation 3:1 phenotypic ratio for the F2 BUT… only the males had white eyes

All females had red eyes, and half the males had red and half had white

Morgan showed that eye color must be linked to its sex

12.2 Sex Linked Genes In mammals: XX – female XY - male

The Y Chromosome Fewer than two dozen genes identified SRY gene (sex-determining region of Y) is the master gene for male sex determination

The X Chromosome Carries more than 2,300 genes Most for nonsexual traits Genes on X chromosome can be expressed in both sexes Gene on either sex chromosome is called a sex-linked gene

Fathers pass all of there X linked alleles to all of their daughters but none to their sons Mothers pass all of there X linked alleles to both daughters and sons If an X linked trait is recessive, a male will express the phenotype, a female will only express it if she is homozygous recessive

Symbols

Sperm Eggs (a) Sperm Sperm Eggs Eggs (b) (c) XNXN XnY Xn Y XN XNXn XNY Figure 12.7 XNXN XnY Xn Y Sperm Eggs XN XNXn XNY XN XNXn XNY (a) XNXn XNY XNXn XnY Figure 12.7 The transmission of X-linked recessive traits XN Y Sperm Xn Y Sperm Eggs XN XNXN XNY Eggs XN XNXn XNY Xn XNXn XnY Xn XnXn XnY (b) (c) 19

Some disorders caused by recessive alleles on the X chromosome in humans Color blindness (mostly X-linked) Duchenne muscular dystrophy Hemophilia 20

Color Blindness Fig. 12-12, p.195

Color Blindness Fig. 12-12, p.195

Hemophilia Fig. 12-11, p.194

X Chromosome Inactivation One X is inactivated in each cell of female mammals (Paternal X in Marsupials, random in Placentals) The inactive X condenses into a Barr body Creates “mosaic” for X chromosomes Governed by XIST gene Dosage compensation theory - shutdown prevents “overdose” of gene products in females

X Chromosome Inactivation Fig. 15-5, p.234

X chromosomes Allele for orange fur Early embryo: Allele for black fur Figure 12.8 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 12.8 X inactivation and the tortoiseshell cat 27

Concept 12.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome Genes located on the same chromosome are called linked genes Degree of linkage varies with distance between loci 28

Crossover Frequency Proportional to the distance that separates genes B C D Crossing over will disrupt linkage between A and B more often than C and D In-text figure Page 178

Complete linkage: Off spring will all look like a parent, no recombination of genes (due to crossing over) occurs

Complete Linkage A B a b x Parents: A B a b AB ab F1 offspring: All AaBb meiosis, gamete formation Equal ratios of two types of gametes: A B a b Figure 11.15 Page 178 50% AB 50% ab

Incomplete linkage: produces new combinations of the genes in the offspring Due to crossing over of homologous chromosomes in between the linked genes Demonstrates an exception to Mendal’s laws

Incomplete Linkage AC ac A C a c x Parents: A C a c F1 offspring: All AaCc meiosis, gamete formation A a A a Unequal ratios of four types of gametes: C c c C parental genotypes recombinant genotypes Figure 11.15 Page 178

 When in sweet peas a cross is made between blue flower and long pollen (BBLL) with red flower and round pollen (bbll) in F1 expected blue flower and long pollen (BbLl) heterozygous condition is expressed.

However, test cross between blue and long (BbLl) and double recessive (bbll) gave blue long (43.7%), red round (43.7%), blue round (6.3%) and red long (6.3%). The parent combinations are 87.4% are due to linkage in genes on two homologous chromosomes, while in case of new combinations (12.6%) the genes get separated due to breaking of chromosomes at the time of crossing over in prophase-I of meiosis. New combinations in the progeny appeared due to incomplete linkage 

Morgan provided evidence with crossing fruit flies See page 237

b vg b vg F1 dihybrid female and homozygous recessive male Figure 12.UN01 b vg b vg F1 dihybrid female and homozygous recessive male in testcross b vg b vg b vg b vg Figure 12.UN01 In-text figure, testcross, p. 234 Most offspring or b vg b vg 37

F1 dihybrid testcross b vg+ b vg Wild-type F1 dihybrid (gray body, Figure 12.10b F1 dihybrid testcross b vg+ b vg Wild-type F1 dihybrid (gray body, normal wings) Homozygous recessive (black body, vestigial wings) b vg b vg 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 Figure 12.10b Chromosomal basis for recombination of linked genes (part 2: testcross) b vg Recombinant chromosomes Meiosis II b+ vg+ b vg b+ vg b vg+ b vg Eggs Sperm 38

Parental-type offspring Recombinant offspring Figure 12.10c Recombinant chromosomes b vg+ b vg b vg b vg Eggs 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 Figure 12.10c Chromosomal basis for recombination of linked genes (part 3: testcross offspring) Sperm Parental-type offspring Recombinant offspring Recombination frequency 391 recombinants   100  17% 2,300 total offspring 39

A linkage map - genetic map of chromosome based on recombination frequencies Distances expressed as map units; one map unit represents a 1% recombination frequency 40

Results Recombination frequencies 9% 9.5% Chromosome 17% b cn vg Figure 12.11 Results Recombination frequencies 9% 9.5% Chromosome 17% Figure 12.11 Research method: constructing a linkage map b cn vg 41

Abnormal Chromosome Number nondisjunction, pairs of homologous chromosomes do not separate during meiosis result, - one gamete carries extra chromosome, and another gamete receives none Video: Nondisjunction 42

Nondisjunction of homo- logous chromosomes in meiosis I (b) Figure 12.13-3 Meiosis I Nondisjunction Meiosis II Non- disjunction Gametes Figure 12.13-3 Meiotic nondisjunction (step 3) n  1 n  1 n − 1 n − 1 n  1 n − 1 n n Number of chromosomes (a) Nondisjunction of homo- logous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II 43

Aneuploidy results from fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome 44

A monosomic zygote has only 1 copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome 45

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 46

(a) Deletion A deletion removes a chromosomal segment. (b) Duplication Figure 12.14a (a) Deletion A deletion removes a chromosomal segment. (b) Duplication Figure 12.14a Alterations of chromosome structure (part 1: deletion and duplication) A duplication repeats a segment. 47

An inversion reverses a segment within a chromosome. Figure 12.14b (c) Inversion An inversion reverses a segment within a chromosome. (d) Translocation Figure 12.14b Alterations of chromosome structure (part 2: inversion and translocation) A translocation moves a segment from one chromosome to a nonhomologous chromosome. 48

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 49

Figure 12.15 Figure 12.15 Down syndrome 50

Down Syndrome Fig. 12-17, p.199

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 Females with trisomy X (XXX) have no unusual physical features except being slightly taller than average 52

It is the only known viable monosomy in humans Monosomy X, called Turner syndrome, produces X0 females, who are sterile It is the only known viable monosomy in humans 53

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 disabled and has a catlike cry; individuals usually die in infancy or early childhood 54

Deletion Cri-du-chat Fig. 12-13, p.196

Disorders Caused by Structurally Altered Chromosomes Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes 56