Ch 15.1-15.4. CHROMOSOMES & INHERITANCE Locating genes on chromosomes T. H.

Morgans studies with fruit flies Incomplete linkage - crossing over Alteration in chromosome number Changes in large portions of a chromosome Review Monday in UNLH 1000 (Exam W in class) 6:10 (Paine) 9 p.m. (Morse starts midway) Paine and Morse office hours: T, W 2:10-4:00 Practice exam questions on Ilearn today (Paine answers up just before the review session) 1 !

Overview: Locating Genes on Chromosomes

A century ago the relationship between genes and chromosomes was not obvious 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

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Fig. 15.1. Fluorescent yellow dye used to tag a specic gene on homologous chromosomes (key genes physical location)!

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P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr)

Meiosis Fertilization

See Fig. 15.2 What we now know about meiosis and linkage explains Mendels Laws of Segregation and Independent Assortment
LAW OF SEGREGATION

Gametes All F1 plants produce yellow-round seeds (YyRr)

F1 Generation

Meiosis Meiosis LAW OF INDEPENDENT ASSORTMENT Two equally probable arrangements of chromosomes at metaphase I Anaphase I

Metaphase II

Gametes

F2 Generation

An F1 x F1 cross-fertilization

Fertilization among the F1 plants

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Morgans Experimental Evidence: Scientific Inquiry

The first solid evidence associating a specific gene with a specific chromosome came from T. H. Morgan (Columbia University) Morgans experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendels heritable factors

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Morgans Choice of Experimental Organism

Characteristics that make fruit flies a very convenient organism for genetic studies: Several hundred offspring from a single pair A generation can be bred every two weeks Small amount of space, cost for rearing They have only four pairs of chromosomes; chromosomes easily visible with a microscope

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 Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes w = white-eye mutant w+ = wild type (red eye)

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Correlating Behavior of a Genes 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-eye mutant allele must be located on the X chromosome Morgans finding supported the chromosome theory of inheritance 8
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Sex-linked Inheritance
Figure 15.3 T. H. Morgans first mutant - whited-eyed Drosophila melanogaster.

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Figure 15.4

Sex-linked inheritance

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Males are the heterogametic sex.

Females are the homogametic sex. w+ - wild type (red eye) w - mutant (white eye)

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Figure 15.4

Sex-linked inheritance

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Males are the heterogametic sex.

Females are the homogametic sex. w+ - wild type (red eye) w - mutant (white eye)

All F1 progeny have red eyes.

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See Figure 15.4

Sex-linked inheritance

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Males are the heterogametic sex.

Females are the homogametic sex. w+ - wild type (red eye) w - mutant (white eye)

All F1 progeny have red eyes.

Why do white eyes disappear in the F1? Because it is a recessive AND sex-linked trait (on the X chromosome)
White-eyed males reappear in the F2 generation.

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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 (only 78 identified so far on human Y) Humans: 2n = 46 chromosomes (23 homologous pairs); Fruit flies: 2n = 8 Genes located on the same chromosome that tend to be inherited together are called linked genes

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Recombination of Linked Genes: Crossing Over

Morgan discovered that genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypes Morgan proposed that some process must sometimes break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes

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Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance

In humans and other animals, there is a chromosomal basis of sex determination An organisms sex is an inherited phenotypic character determined by the presence or absence of certain chromosomes

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The Chromosomal Basis of Sex

In humans and other mammals, there are two varieties of sex chromosomes, X and Y; females are XX, males XY SRY (Sex-determining Region of Y) is required for development of the testes in males In the absence of SRY, the gonads develop into ovaries in females Some animals have alternative methods of sex determination

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Fig. 15.6
Sperm

Parents

Ova

Zygotes (offspring) The X-Y system

The X-0 system

The Z-W system

The haplo-diploid system

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California red scale on oranges (#1 pest of citrus)

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Aphytis melinus parasitoid (from Pakistan in the 1950s) stinging a scale

X Inactivation in Female Mammals

One X chromosome in each cell in females becomes almost completely inactivated during embryonic development Inactive X condenses into a compact body called a Barr body (most genes are not expressed in this X) This occurs randomly in each embryonic cell thus, females are a mosaic of two cell types (X from father vs. mother) In the ovaries, Barr-body chromosomes are reactivated in the cells that will give rise to eggs so every female gamete has an active X chromosome

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X Inactivation Tortoiseshell Cats

Tortoiseshell (calico) female cats mottled with patches of orange, cream, black, brown, red, or chocolate Markings are usually asymmetrical Primary gene for coat color can be masked by a co-dominant gene for orange color located on the X chromosome Third gene softens colors (orange to cream, black to gray, etc.)

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Inheritance of Sex-Linked Genes

The sex chromosomes have genes for many characters unrelated to sex A gene located on either sex chromosome is called a sex-linked gene (by convention, typically on X in humans) Sex-linked genes follow specific patterns of inheritance

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Disorders caused by recessive alleles on the X chromosome in humans include: Color blindness (ca. 1 in 10 males; understand why it is rare in females calculate what percent) Duchenne muscular dystrophy (1 in 3,500 males in the U.S.) Hemophilia (1 in 10,000 males)

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MUTATION

Initial population

Mutation =
A change in the genetic material of a cell or virus Mutation is the ultimate source of all genetic variation!

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Normal Mouse

Tails as long as 23 cm have been reported in humans

Normal Mouse Mutant Kinky Tail Mouse

Mutant

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normal (wild type) Drosophila melanogaster

White eyes!

Stubby wings!

Dark body!

Eyes absent!

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Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders
Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

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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

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CHROMOSOMAL MUTATIONS (Number)

Mutation supplies the raw material for evolution

See Figure 15.13

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

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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

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Down Syndrome
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 well explained

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CHROMOSOMAL MUTATIONS (Number) Dosage =

The number of copies of a given gene present in a cell or nucleus

3 copies of chromosome 21 (trisomy 21)

Down Syndrome

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 A trisomic zygote has three copies of a particular chromosome A monosomic zygote has only one copy of a particular chromosome Polyploidy is a condition in which an organism has more than two complete sets of chromosomes

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CHROMOSOMAL MUTATIONS (Polyploidy)

Haploid = one set of chromosomes in the cell (1n)

Diploid = 2 sets of chromosomes in the cell, one from each parent (2n)

Polyploid = cell or organism containing more than 2 sets of chromosomes.

Oenothera gigas (4n = 28)

- Thousands of plant species are polyploid - Rare in vertebrates

Mutation supplies the raw material for evolution

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First polyploid vertebrate discovered in Chile a tetraploid burrowing rodent (1999)!

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CHROMOSOMAL MUTATIONS (Structure)

(REVIEW of MEIOSIS + MITOSIS -- SEE pp. 250-259 and FIGURE 13.8)

Figure 15.14

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Key to Impacts -- Where Mutations Occur Where in the genome might mutations occur?

* Intron -- non-coding region of a eukaryote gene * Most mutations occur here * Potentially little impact (modulate gene expression?) * Exon -- coding region of a eukaryote gene * Crossing over that includes part of an intron and an exon (See Fig. 17.13) * This could lead to new proteins * Most would be non-beneficial * An occasional beneficial change (in a particular environment)

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Hemoglobin (4 subunits)

There are several globin genes within a single mammalian genome.

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Practice Question 1 T. H. Morgan found a white-eye mutation in male fruit flies that was recessive, with the allele located on the X chromosome. Assume males are the heterogametic sex (XY). What phenotypes result from crossing a white eye female and a wild type male?

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Practice Question 2 In Mendels studies, the allele for round seed was dominant over that for wrinkled seed and the unlinked allele for yellow seed was dominant over green seed. What offspring are produced by a dihybrid cross of a wrinkled green seed by the double heterozygous genotype?

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Practice Question 3 You are running a cross involving 4 different genes. Three different chromosomes are involved and only the A/a and C/c genes are linked. With diploid parents AaBbccDd x AaBbcCdd (Ac and aC are linked in the second parent) and no crossing over, what are the odds of progeny with genotypes (a) aaBbccdd, (b) aabbCcDd, (c) AABbccdd?

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