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your exam!- Hand your exam and Scantron in at the end- Answer keys will be posted (NO PICTURES!)- Grades will be posted ASAP

DO NOT CHEAT!

CHAPTER 3 PART 2Genetics

3.3 The Chromosome Theory of Heredity Proposes That Genes Are Carried on Chromosomes

• Sutton and Boveri proposed that chromosome behavior in meiosis mirrors hereditary transmission of genes• The Boveri-Sutton Chromosome

Theory

• Correctly explains the mechanism underlying Mendelian Genetics by identifying chromosomes as the paired factors required by Mendel’s Laws. States that chromosomes are linear structures with genes located at specific sites called loci

WalterSutton

TheodorBoveri

SOMEONE WAS SKEPTICAL OF THE ‘GENE HYPOTHESIS’…

Thomas Hunt Morgan was skeptical:

Pea plants are domesticated, what happens in the real world? With a wild, natural species?

What species did he find?

3.3 The Chromosome Theory of Heredity Proposes That Genes Are Carried on Chromosomes

• Morgan studied fruit flies, Drosophila melanogaster, to test Mendel’s rules on a natural, rather than domesticated, species • Hung buckets of rotting fruit in trees in the then rural Long Island to attract fruit

flies. Found them easy to work with, and have a life cycle of 12-14 days.

• The term “wild type” signifies the phenotype most common in a population

http://www.youtube.com/watch?v=LOGeTdcnqFM

Thomas Hunt Morgan

• Although at first wild-type phenotypes prevailed, over several years, Morgan’s lab members found numerous phenotypic variants and analyzed these in controlled crosses

• He concluded from his results that genes were carried on chromosomes (independently proposed)

• Great mentor, encouraged the use of fruit fly in students, several mentees went on to win Nobel Prizes

• His graduate student, then wife and mother of his four children, Lilian Mogand made important contributions in the laboratory (X-linked inheritance).

• Strongly against eugenics movement

• Unraveled many basic principles of genetics and inheritance.

Chromosomal Basis of Sex

• Nettie Stevens (working with Tenebrio molitor beetles): sex-dependent hereditary differences are due to the presence of two X chromosomes in females and an X and a smaller Y chromosome in males• Diploid cells of females contained 20 large

chromosomes; males contained 19 large chromosomes and one small one

• Half of the sperm of males contained 10 large chromosomes and the other half had 9 large and one small chromosome

• Sex-linked inheritance refers to transmission of traits on sex chromosomes Mealworm

The White-Eye Mutant

• The first mutant identified in Morgan’s lab was a male with white eyes instead of the normal red color

• The mutant white-eyed male was crossed to a normal red-eyed female, producing many F1, all with red eyes

• Thus the white-eyed mutant allele was what?

NOT a normal 3:1! Only the males have white eyes!

Continued crosses…

• When the original white-eyed male was crossed to one of the F1 females, a 1:1 ratio of white eyes and red eyes was observed in both male and female offspring

Reciprocal Cross

• A cross between a white-eyed female and red-eyed male produced red-eyed female and white-eyed male F1; a cross between these produced F1 with red and white eyes in equal frequencies among both male and female progeny

The Gene for Eye Color Is on the X Chromosome

• The differences in phenotype according to gender are not anticipated according to Mendel’s laws

• The transmission of the X chromosome can account for the results obtained by Morgan’s lab

• X-linked inheritance is the term for traits carried on the X chromosome; males have only one X and so are called hemizygous for X-linked traits

X & Y chromosome segregation of cross A, B, C.

-Allele genotype is written as a superscript to the X chromosome (XW+, XW)-Hemizygous Y chromomsomes do not carry a genotype-Use a Punnet square to cross two sex chromosomes exactly as one would for two alleles

Figure 3.18

Let’s draw one..Heterozygous red female x white male

Exceptional phenotypes!

• Morgan’s work led him to propose the chromosome theory of heredity

• Calvin Bridges studied “exceptional phenotypes”; very rare cases of unexpected eye color

• Observed exceptional phenotypes: in a cross between a white-eyed female and red-eyed male, unexpected rare (1/2,000) offspring were observed: females with white eyes or males with red eyes (only red females and white males are predicted to occur)

• What was happening to

the X chromosome?

What is this called?

Nondisjuntion

• Bridges saw that the exceptional females had three X chromosomes and one Y; and the exceptional males had just one X chromosome

• Failed chromosome separation is nondisjunction

3.4 Sex Determination Is Chromosome and Genetic

• Chromosomal sex is the presence of chromosomes characteristic of each sex and is determined at the moment of fertilization

• Phenotypic sex is the internal and external morphology of each sex, and results from differences in gene expression -Females have two X

chromosomes and males have one X chromosome-Thus in flies; Males: X0, XYY, or XY (normal) Females are XXY or XX (normal)

• Sex is determined by the X : A ratio

• -X =number of X chromosomes;

A = number of haploid sets of autosomes

This ratio influences the actions of three sex-determing genes:

Deadpan, Sisterless and Sex-lethal genes

(complicated!)

• XX = female, XY= male. • The X chromosome contains genetic

information essential for both sexes; at least one copy of an X is required. • Absence of X is lethal

• The male-determining gene is located on the Y chromosome. A single Y, even in the presence of several X’s, will still produces a male phenotype.• SRY gene on the Y chromosome

determines maleness• The absence of Y results in a female

phenotype.

Sex Determination in Humans

Generation of male traits in humans

SRY Gene (Sex-determing Region Y)

• Expression of SRY initiates testicular development of the undifferentiated gonads

• The absence of SRY expression allows the default, female state, to develop

22

• SRY is a transcription factor needed for male-specific gene expression• Issues with the sex genes

themselves can alter the male phenotype• Androgen-insensitivity

syndrome• Caused by the defective androgen

receptor• Can be mild to complete

androgen insensitivity• XY ‘females’

SRY is a transcription factor

• XX = female, XY= male. • SRY gene on the Y chromosome determines maleness• Turner syndrome: XO; 1/3000 female births

• Amenorrhea, sterility, web necked, horse shoe kidney

• Klinefelter syndrome: XXY, or XXXY, or XXXXY, or XXYY; 1/1000 male birth• infertility, gynechomastia, hypogonadism

• Poly-X females: 1/1000 female births• Tall stature, menstrual irregularity, possible reduction of fertility

Nondisjuntion in humans• Aneuploidy: Uneven number of chromosomes

Cover in Ch. 13!

Diversity of Sex Determination

• A different system, the Z/W system, is used by birds, some reptiles, some fish, butterflies, and moths

• In this system females have two different sex chromosomes (ZW) and males have two sex chromosomes that are the same (ZZ)

Z-Linked Inheritance

• Barred feathers: Z-linked dominant allele (ZB)

• Non-barred feathers is recessive (Zb)

• In sex-linked traits, sexes are NOT affected equally (F2)

• How do we verify that sex is affecting outcome?

Z-Linked Inheritance

• Reciprocal Cross (reverse sexes) yields different results from the previous cross. This indicates that feather form is sex-linked.

• Heterogametic sex: the sex chromosomes do not match, and thus the gametes produced by that sex do not match.

In humans, the males (XY) are the heterogametic sex. Males produce both X and Y gametes

• Homogametic sex: sex chromosomes match and will produce the same sex-ed gametes

• In many species (birds, fish, reptiles) females can be heterogametic sex (ZW system)

Heterogametic vs Homogametic Sexhttp://www.cals.ncsu.edu/course/ent425/

GametesX & Y

GametesX & X

• Sex can also be determined by the number of chromosome sets

• In haplodiploidy, males develop from unfertilized eggs and are haploid (n), females develop from fertilized eggs and are diploid (2n).

Haplodiploidy

Environmental Sex Determination

• Sex is determined by the temperature the eggs are incubated at

• In the red-eared slider turtle, eggs above 30⁰ C produce all females

• In the snapping turtle, eggs below 22⁰ C or above 28⁰ C will be female. Between 25-27⁰ C males predominate

Temperature-dependent sex determination in three reptile species: the American alligator (Alligator mississippiensis), the red-eared slider turtle (Trachemys scripta elegans), and the alligator snapping turtle (Macroclemys temminckii). (After Crain and Guillette 1998.)

Environmental Sex Determination• Sex is determined in limpets (sea snails) by its position on the stack

3.5 Human Sex-Linked Transmission Follows Distinct Patterns

• In X-linked recessive inheritance, females homozygoous for the recessive allele or males hemizygous for it display the recessive phenotype

• In X-linked dominant traits, heterozygous females and males hemizygous for the dominant allele express the dominant phenotype

• Hemizygous males display any allele on their single X whether the allele is recessive or dominant in females

Features of X-Linked Recessive Inheritance

1. Many more males than females have the trait due to hemizygosity

1. Many more males than females have the trait due to hemizygosity

2. A recessive male mated to a homozygous dominant female produces all offspring with the dominant phenotype, and all female offspring are carriers

3. Matings of recessive males with carrier females give half dominant and half recessive offspring of both sexes

4. Matings of homozygous recessive females with dominant males produce all dominant (carrier) female offspring and all recessive male offspring

X-Linked Recessive#2

#3

#4

Hemophilia A Is an X-Linked Recessive Trait

• Hemophilia A is caused by a mutation in the factor VIII gene on the X chromosome

• The mutant allele produces a nonfunctional blood-

clotting protein

• A de novo (newly occurring) mutation is thought to have been passed from Queen

Victoria of England to some of her offspring

1. Many more males than females have the trait due to hemizygosity

X-Linked Dominant Trait Transmission

X-Linked Dominant Trait Transmission

• The distinctive characteristics of X-linked dominant traits are

1. Heterozygous females mated to wild-type males transmit the dominant allele to half their progeny of each sex

2. Dominant males mated to homozygous recessive females pass the trait to all their daughters and none of their sons

3. The trait appears equally frequently in males and females

Congenital Hypertrichosis

• Congenital hypertrichosis (CGH) is a rare X-linked dominant disorder in humans

• It leads to a large increase in the number of hair follicles on the body, and males and females have more body hair than normal

1. Heterozygous females mated to wild-type males transmit the dominant allele to half their progeny of each sex

2. Dominant males mated to homozygous recessive females pass the trait to all their daughters and none of their sons

3. The trait appears equally frequently in males and females

Modified pedigree with CGH

#1? #2

Y-Linked Inheritance

• Y-linked traits are transmitted in an exclusively male-to-male pattern

• In mammals, there are fewer than 50 genes on the Y chromosome; many play roles in male sex determination or development

• Though males have only one Y chromosome, they are not hemizygous for it, as most of the genes on the Y are present in two copies

The Pseudoautosomal Region

• Two small regions of homology, the pseudoautosomal regions (PAR1 and PAR2), exist between the X and Y chromosomes

• These allow homologous pairing between the X and Y at meiosis

• There is evidence that crossing over occurs within these regions during meiosis

http://php.med.unsw.edu.au/embryology

3.6 Dosage Compensation Equalizes Dosage of Sex-Linked Genes

• In organisms with sex chromosomes, there is a gender imbalance between the copy number of genes on the sex chromosomes

• Any mechanism that compensates for the difference in number of copies of genes between males and females is called dosage compensation

Random X-Chromosome Inactivation in Placental Mammals

• Early in mammalian development, one of two X chromosomes in each female somatic cell is randomly inactivated

• The random X inactivation hypothesis is also called the Lyon hypothesis, after Mary Lyon, who first proposed it (1962)

• The inactive X chromosome is visible near the nuclear wall, as a condensed Barr body, first visualized by Murray Barr (1949)

Female Mammals Are Mosaics

• Once X inactivation has occurred in a cell, it is permanent in all the descendants of that cell

• Female mammals are mosaics of two populations of cells; one expresses the maternal X and the other the paternal X

• Alleles of both chromosomes are expressed approximately equally over the whole organism

Calico and Tortoiseshell Cats Are Visibly Mosaic

• In cats, the X chromosome carries a gene responsible for coat color

• One allele specifies a black color; the other a yellow color

• X inactivation in heterozygous females leads to a pattern of orange and black patches that is unique to each individual

Mechanism of X Inactivation

• Random X inactivation requires an X-linked gene called Xist (X-inactivation-specific-transcript)

• The gene produces large RNA molecules that spread out and cover (or paint) the chromosome to be inactivated

• Xist can only act on the chromosome from which it is being transcribed and not the homolog (i.e., it acts in cis)

epigenie.com

Questions?