Chapter 15 The Chromosomal Basis of Inheritance Gene

Chapter 15 The Chromosomal Basis of Inheritance

Gene Location • Genes are located on chromosomes in specific spots (loci) Figure 15. 1

Behavior of Chromosomes • Mendelian inheritance has its physical basis in the behavior of chromosomes • Linkage between chromosomes and genes proposed in 1900 s. • The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

Chromosomal Theory of Inheritance • Mendelian genes have specific loci on chromosomes • Chromosomes undergo segregation & independent assortment

Morgan’s Choice of Experimental Organism • Thomas Hunt Morgan • Provided convincing evidence that chromosomes are the location of Mendel’s heritable factors • Morgan worked with fruit flies • Because they breed at a high rate • A new generation can be bred every two weeks • They have only four pairs of chromosomes

• Morgan first observed wild type, or normal, phenotypes that were common in the fly populations • Traits alternative to the wild type are called mutant phenotypes Wild type Mutant type 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 F 1 generation all had red eyes • The F 2 generation showed the 3: 1 red: white eye ratio, but only males had white eyes What can you conclude about the location of the gene for eye color in fruit flies?

Morgan’s conclusion That the white-eye mutant allele must be located on the X chromosome EXPERIMENT Morgan mated a wild-type (red-eyed) female with a mutant white-eyed male. The F 1 offspring all had red eyes. P Generation X F 1 Generation Morgan then bred an F 1 red-eyed female to an F 1 red-eyed male to produce the F 2 generation. RESULTS The F 2 generation showed a typical Mendelian 3: 1 ratio of red eyes to white eyes. However, no females displayed the white-eye trait; they all had red eyes. Half the males had white eyes, and half had red eyes. F 2 Generation Figure 15. 4

CONCLUSION Since all F offspring had red eyes, the mutant 1 white-eye trait (w) must be recessive to the wild-type red-eye trait (w+). Since the recessive trait—white eyes—was expressed only in males in the F 2 generation, Morgan hypothesized that the eye-color gene is located on the X chromosome and that there is no corresponding locus on the Y chromosome, as diagrammed here. P Generation W+ X X W+ W+ W+ W W Ova (eggs) F 1 Generation X X Y Sperm W+ W W+ Ova (eggs) F 2 Generation Sperm W+ W+ W+ W W W+

Linked genes • Tend to be inherited together because they are close on the same chromosomes • Each chromosome has 100’s or 1000 s of genes For two genes that are not inherited together, what percentage of offspring would have parental phenotypes? What about two genes that are on the same chromosome?

More of Morgan’s experiments P Generation (homozygous) EXPERIMENT Morgan first mated true-breeding x Wild type wild-type flies with black, vestigial-winged flies to produce Double mutant (gray body, heterozygous F 1 dihybrids, all of which are wild-type in (black body, normal wings) appearance. He then mated wild-type F 1 dihybrid females with vestigial wings) b+ b+ vg+ black, vestigial-winged males, producing 2, 300 F 2 offspring, which he “scored” (classified according to phenotype). Double mutant (black body, vestigial wings) b b vg vg F 1 dihybrid Double mutant TESTCROSS (wild type) (black body, x (gray body, vestigial wings) normal wings) CONCLUSION If these two genes were on different chromosomes, the alleles from the F 1 dihybrid would sort into gametes independently, and we would expect to see equal numbers of the four types of offspring. If these two genes were on the same chromosome, we would expect each allele combination, B+ vg+ and b vg, to stay together as gametes formed. In this case, only offspring with parental phenotypes would be produced. Since most offspring had a parental phenotype, Morgan concluded that the genes for body color and wing size are located on the same chromosome. However, the production of a small number of offspring with nonparental phenotypes indicated that some mechanism occasionally breaks the linkage between genes on the same chromosome. Figure 15. 5 Double mutant (black body, vestigial wings) b b vg vg b+ b vg+ vg RESULTS b vg b+vg+ b vg 965 944 Wild type Black(gray-normal) vestigial b+ vg b vg+ 206 Grayvestigial 185 Blacknormal Sperm b+ b vg+ vg b b vg vg b+ b vg vgb b vg+ vg Parental-type offspring Recombinant (nonparental-type) offspring

Morgan’s conclusion • Linked genes - close together on the same chromosome and do not assort independently • Unlinked genes - either on separate chromosomes or are far apart on the same chromosome & assort independently b+ vg+ b vg X Parents in testcross Most offspring b vg b+ vg+ b vg or b vg

Recombination of Unlinked Genes: Independent Assortment of Chromosomes • When Mendel followed the inheritance of 2 characters • He observed that some offspring have combinations of traits that do not match either parent in the P generation Gametes from yellow-round heterozygous parent (Yy. Rr) YR Gametes from greenwrinkled homozygous recessive parent (yyrr) yr Yr y. R Yyrr yy. Rr yr Yy. Rr yyrr Parentaltype offspring Recombinant offspring

Unlinked genes • Recombinant offspring • show new combinations of the parental traits • If 50% of offspring are recombinants • Geneticists say that there is a 50% frequency of recombination

Recombination of Linked Genes: Crossing Over • Despite gene linkage, recombinant phenotypes appeared. What is crossing over and how does it explain the existence of these recombinant phenotypes?

Testcross parents b+ vg+ Gray body, normal wings (F 1 dihybrid) b vg Replication of chromosomes b+ Meiosis I: Crossing over between b and vg loci produces new allele combinations. Gametes Replication of chromosomes b vg vg b b+ vg b b b vg Meiosis II: Segregation of chromatids produces recombinant gametes with the new allele combinations. Black body, vestigial wings (double mutant) vg vg Meiosis I and II: Even if crossing over occurs, no new allele combinations are produced. Recombinant chromosome Ova Sperm b+vg+ b vg b+ vg b vg+ b vg b+ vg+ Testcross offspring Sperm b vg Figure 15. 6 965 Wild type (gray-normal) b+ vg+ b vg b+ vg 944 Blackvestigial b vg+ 206 Grayvestigial b+ vg+ b vg+ Ova 185 Blacknormal Recombination b vg+ frequency b vg Parental-type offspring Recombinant offspring = 391 recombinants 2, 300 total offspring 100 = 17%

Linkage Mapping: Using Recombination Data: Scientific Inquiry • Genetic map • Ordered list of genetic loci on a particular chromosome • Linkage map • Actual map of a chromosome based on recombinant frequencies

• Many fruit fly genes were mapped initially using recombination frequencies I Y II X IV III Mutant phenotypes Short aristae Black body 0 Long aristae (appendages on head) Figure 15. 8 Cinnabar eyes 48. 5 57. 5 Gray body Red eyes Vestigial wings 67. 0 Normal wings Wild-type phenotypes Brown eyes 104. 5 Red eyes

The Chromosomal Basis of Sex • An organism’s sex is an inherited phenotypic character determined by the presence or absence of certain chromosomes • In humans and other mammals • There are two varieties of sex chromosomes, X & Y

Different systems of sex determination 22 + XX 22 + X 76 + ZW 76 + ZZ 16 16 (b) The X– 0 system (c) The Z–W system (Diploid) Figure 15. 9 b–d (d) The haplo-diploid system (Haploid)

Inheritance of Sex-Linked Genes • sex chromosomes • Genes for many characters unrelated to sex • genes on either sex chromosome • Sex-linked genes • Follow specific pattern of inheritance

Xa. Y 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. Ova Xa Y XA XAXa XAY XA XAYa XAY XAXa Sperm XAY (b) If a carrier 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. Sperm XA Ova Y XA XAY Xa Xa. YA Xa. Y (c) XAXa 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. Sperm Ova Figure 15. 10 a–c Xa. Y Xa Y XA XAXa XAY Xa Xa. Y

Sex-linked disorders • recessive alleles on the X chromosome can cause: • Color blindness • Duchenne muscular dystrophy • Hemophilia

X inactivation in Female Mammals • In mammalian females • 1 of the 2 X chromosomes in each cell is randomly inactivated during embryonic development • Usually results in half of cells exhibiting inactivation of either X chromosome

• If a female is heterozygous for a particular gene located on the X chromosome she will be a mosaic for that character Two cell populations in adult cat: Active X Early embryo: X chromosomes Allele for black fur Figure 15. 11 Cell division Inactive X and X chromosome Inactive X inactivation Active X Orange fur Black fur

Chromosomal Disorders • Alterations of chromosome number or structure cause some genetic disorders • Large-scale chromosomal alterations • usually lead to spontaneous abortions or sometimes developmental disorders

Abnormal Chromosome Number • nondisjunction • Pairs of homologous chromosomes don’t separate normally during meiosis • Gametes with 2 or 0 copies of a certain chromo • Can occur during meiosis I or II Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n+1 Figure 15. 12 a, b n+1 n 1 n+1 n – 1 n– 1 Number of chromosomes (a) Nondisjunction of homologous chromosomes in meiosis I n n (b) Nondisjunction of sister chromatids in meiosis II

Nondisjunction • Aneuploidy - fertilization of gametes in which nondisjunction occurred • offspring have an abnormal # of a particular chromosomes • zygote is trisomic • 3 copies of a chromo • zygote is monosomic • 1 copy of a chromo

Polyploidy • More than 2 complete sets of chromosomes in an organism • Triploidy (3 n) or tetraploidy (4 n) • Uncommon in mammals Figure 15. 13

Alterations of Chromosome Structure • Breakage of a chromosome • 4 different changes in chromosome structure • • Deletion Duplication Inversion Translocation

Alteration of chromosome structure (a) A deletion removes a chromosomal segment. (b) A duplication repeats a segment. (c) An inversion reverses a segment within a chromosome. (d) A translocation moves a segment from one chromosome to another, nonhomologous one. In a reciprocal translocation, the most common type, nonhomologous chromosomes exchange fragments. Nonreciprocal translocations also occur, in which a chromosome transfers a fragment without receiving a fragment in return. Figure 15. 14 a–d A B C D E F G H Deletion Duplication Inversion A B C E F G H A B C D E A D C B E F G H M N O C D E Reciprocal translocation M N O P Q R A B P Q F G H R F G H

Human Disorders Due to Chromosomal Alterations • Down syndrome • Usually an extra chromosome 21; trisomy 21 • Cri du chat • deletion in a chromosome • Some cancers • caused by translocations of chromosomes

Aneuploidy of Sex Chromosomes • Nondisjunction of sex chromosomes • Produces a variety of aneuploid conditions • Klinefelter syndrome • extra X in a male, XXY • Turner syndrome • monosomy X, • X 0

Nonstandard inheritance patterns • Some inheritance patterns are exceptions to the standard chromosome theory • 2 normal exceptions to Mendelian genetics • Genes in the nucleus • Genes outside the nucleus

Genomic Imprinting • Genomic Imprinting in mammals • phenotypic effects of some genes depend on which allele is from mom and which is from dad • silencing of certain genes that are “stamped” with an imprint during gamete production • Phenotype for specific genes is always based on same parent

Inheritance of Organelle Genes • Extranuclear genes • genes in organelles in the cytoplasm • inheritance of traits controlled by genes in the chloroplasts or mitochondria • Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg • Some diseases affecting the muscular and nervous systems • Are caused by defects in mitochondrial genes that prevent cells from making enough ATP