Lecture 12 – Mendel and the Gene Idea

In this lecture…. • What’s a gene? • Mendel’s pea plants • Mendel’s hypothesis

– Four laws

• Beyond Mendel – Different levels of dominance – Multiple alleles – One gene producing multiple phenotypes – Multiple genes producing one phenotype – Nature vs. nurture

• Genetic Testing • Punnet Squares

– Monohybrid crosses – Dihybrid crosses

First…let’s define these gene things

• Genome – the full complement of genetic information

• Chromosome – a single molecule of DNA. There are 23 chromosomes in the haploid genome

• Gene – a single unit within the genome that encodes for a trait

• Nucleotide – makes up genes, chromosomes, and genomes

Genome = Book Chromosome = the separate chapters of

the book Gene = a single word

Nucleotide = a single letter

What a gene looks like:

1 agtgaaatat tttaagatcc ttagaaatat aatatcaata ctatgccatt ggaggattgg 61 agggttgtga aaaacaaaca agcaaacaaa aaacggagtc ttcactgctt gatggaggct 21 tttgattcag tattggaatt ctttatccag tagttatccc ctttctatat tcatttggat 181 aaagctttcc tgggtataga acccacttag cctgcaagat tccatcccag agcaattgat 614401 ttcaactctt catgtcatga tgatagcact gaagaggtca tcaatttgaa agtggactag 614461 ctg

Definition of a gene

• Evolutionary biologist: a self-replicating unit within the DNA

that is acted on by evolutionary forces as it is passed through generations

• Molecular biologist: a segment of DNA that begins and ends

with specific nucleotide sequences

• Biochemist: A portion of DNA that is translated into a protein product

• Student: that DNA stuff

For us: a gene is a word

Discrete

Very specific spelling

Produces a specific sound (protein)

Mendel was a big thinker

• Genetics is the study of inheritance, or how genes are passed along generations

– Genomics is the study of all genes and their interactions with themselves and their environment

Why do we need to know about Mendel?

• “Father of Genetics”

• Mendel laid down the basic laws of inheritance

• He did this by experimenting with pea plants

Why pea plants?

• Advantages of pea plants for genetic study – There are many varieties with distinct heritable

features, or traits (such as flower color)

– Mating can be controlled

– Each flower has sperm-producing organs (stamens) and egg-producing organ (carpel)

– It was easy to control the pollination of the plants

Model Organisms

Some vocabulary

• In a typical experiment, Mendel mated two contrasting, true-breeding varieties, a process called hybridization

• The true-breeding parents are the P generation

• The hybrid offspring of the P generation are called the F1 generation

• When F1 individuals self-pollinate or cross- pollinate with other F1 hybrids, the F2 generation is produced

Figure 14.3-1

P Generation

EXPERIMENT

(true-breeding parents) Purple

flowers White

flowers

Figure 14.3-2

P Generation

EXPERIMENT

(true-breeding parents)

F1 Generation (hybrids)

Purple flowers

White flowers

All plants had purple flowers

Self- or cross-pollination

Figure 14.3-3

P Generation

EXPERIMENT

(true-breeding parents)

F1 Generation (hybrids)

F2 Generation

Purple flowers

White flowers

All plants had purple flowers

Self- or cross-pollination

705 purple- flowered

plants

224 white flowered

plants

Mendel’s Observations

• Mendel saw that the white color disappeared in the F1 generations

• However, it persisted somehow and came back out in the F2 generation

• Mendel called the purple flower color a dominant trait and the white flower color a recessive trait

Mendel’s Hypothesis

• Mendel developed a hypothesis to explain the 3:1 inheritance pattern he observed in F2 offspring

• Four related concepts make up this model

• These concepts can be related to what we now know about genes and chromosomes

Four Concepts:

Alleles

Everyone inherits two alleles, one from each

parent

Dominant and recessive

alleles

Law of Segregation

First Concept: Alleles

• Alternative versions of genes account for variations in inherited characters • For example, the gene for flower color in pea

plants exists in two versions, one for purple flowers and the other for white flowers

• These alternative versions of a gene are now called alleles

• Each gene resides at a specific locus on a specific chromosome

Loci The physical location of a gene within the genome

Mouse IGH loci map

Second: Two alleles from each parent

• For each trait, an organism inherits two alleles, one from each parent

• The two alleles at a particular locus may be identical, as in the true-breeding plants of Mendel’s P generation

• Alternatively, the two alleles at a locus may differ, as in the F1 hybrids

Homozygous vs. Heterozygous • An organism with two identical alleles for a character

is homozygous for the gene

• An organism that has two different alleles for a gene is heterozygous for the gene

– Unlike homozygotes, heterozygotes are not true-breeding

Third: dominant and recessive alleles

• The dominant allele determines the organism’s appearance

• The recessive allele has no noticeable effect on appearance – The dominant allele masks the effect of the

recessive allele

• In the flower-color example, the F1 plants had purple flowers because the allele for that trait is dominant

How can one allele be dominant over the other?

• There is no one-size fits all answer

– The recessive allele makes a ‘broken’ protein

– The dominant protein stops or slows down the recessive protein

• P53 tetramers

– The dominant protein does something new, or does its normal thing at the wrong time

Red hair and recessive alleles • Red hair is a recessive allele

• A protein called MC1R gets rid of red-colored protein in hair – MC1R is a G-protein coupled receptor

– All it take is a little bit of MC1R to do this

• If the gene for MC1R is ‘broken,’ this protein doesn’t work

• A person must have two damaged MC1Rs to have red hair

Frequency of Dominant Alleles

• Dominant alleles are not necessarily more common in populations than recessive alleles

• For example, one baby out of 400 in the United States is born with extra fingers or toes

• The allele for this unusual trait is dominant to the allele for the more common trait of five digits per appendage

• In this example, the recessive allele is far more prevalent than the population’s dominant allele

Polydactylyl is a dominant trait

Hemmingway Cats

Fourth: Law of Segregation

• The two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes

• Thus, an egg or a sperm gets only one of the two alleles that are present in the organism

• This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis

• This is called the law of segregation

Genotype vs. Phenotype

• Genotype is the genetic makeup

• Phenotype is the physical appearance produced by the genotype

• An organism that is heterozygous for a recessive allele, such as albinism, would exhibit the normal phenotype (normal color) but have the heterozygous genotype

Phenotype

Purple

Purple

Purple

White

3

1

1

1

2

Ratio 3:1 Ratio 1:2:1

Genotype

PP (homozygous)

Pp (heterozygous)

Pp (heterozygous)

pp (homozygous)

Figure 14.6

Keeping your terms straight

• Homozygous – two of the same alleles

• Heterozygous – two different alleles

• Genotype – the genetic composition

• Phenotype – the physical appearance

• A dominant allele is signified by a capital letter

– R for having functioning MC1R

• A recessive allele is signified by a lower-case letter

– r for having defective MC1R

Writing out homozygous vs. heterozygous

A human will have two alleles of a gene – one from each parent

A person homozygous recessive for red hair will have: Genotype: aa Phenotype: red hair A person heterozygous for red hair will have: Genotype: Aa Phenotype: Brown/black hair A person homozygous dominant for red hair will have: Genotype: AA Phenotype: Brown/black hair

Dominant and Recessive Traits in Humans

• Many (in fact, most) human traits don’t follow simple dominant and recessive patterns

• However, there are a few that do:

– Widow’s peak (dominant)

– Attached (dominant) vs. free earlobe (recessive)

– Photic sneeze reflex (dominant)

– Wet (dominant) or dry (recessive) ear wax

– Albinism (recessive)

Widow’s peak

No widow’s peak Attached

earlobe Free

earlobe

Wet earwax Dry earwax

Your classmate’s phenotypes

Dominant Recessive Don’t Know!?

Ear Wax 13 7

Widow’s Peak 2 20

Photic Reflex 2 20

Earlobe 2 20

Albino 22 0

Mendel wasn’t the end of it…

• Inheritance of characters by a single gene may deviate from simple Mendelian patterns:

– When alleles are not completely dominant or recessive

– When a gene has more than two alleles

– When a gene produces multiple phenotypes

– When multiple genes produce one phenotype

When a gene has more than two alleles • Most genes have more than two alleles

• There are three alleles for blood type:

– IA, IB, and I

• IA allele adds an “A” glycoprotein to the surface of red blood cells

• IB has adds a “B” glycoprotein

• i adds no glycoprotein whatsoever

When a gene produces multiple phenotypes

• Most genes have multiple phenotypes, a property called pleiotropy

• Pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as cystic fibrosis and sickle-cell disease

Examples of pleiotropy • The frizzle gene in chickens

– The dominant frizzle gene in chickens produces curled feathers, abnormal body temperatures, high metabolic rate, and high digestive capacity

Examples of pleiotropy • White fur and blue eyes in cats

– 40% of cats with white fur and blue eyes will be deaf

– One particular gene causes the white coat, blue eyes, and deafness, but not all cats get their white coat and blue eyes from this gene

– Pigmentation plays a role in maintaining fluid in ear canals. Animals that lack the pigment also lack ear canal fluid, which causes their ear canals to collapse

Antagonistic pleiotropy

• P53 causes damaged cells to stop reproducing

• It decreases the chance of cancer occurring, but also prevents stem cells from dividing

• P53 increases fitness and reproductive ability early on in life, but decreases fitness later

Different levels of dominance

• Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical

• In incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties

• In codominance, two dominant alleles affect the phenotype in separate, distinguishable ways

Complete dominance • Phenotypes of the heterozygote and the

dominant homozygote are identical

• Traditional Mendelian dominance

• Polydactylyl, albinism

Incomplete dominance

• One allele is incompletely dominant over the other

• This results in a phenotype that is intermediate between the two alleles

• Snapdragon and carnation flower coloring

Codominance • The contributions of two alleles contribute to

the phenotype

• Blood type in humans and roan fur in cattle

Codominance in blood type

Multiple genes having one phenotype

• In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus

• For example, in Labrador retrievers and many other mammals, coat color depends on two genes

• One gene determines the pigment color (with alleles B for black and b for brown)

• The other gene (with alleles C for color and c for no color) determines whether the pigment will be deposited in the hair

Figure 14.12

Sperm

Eggs

9 : 3 : 4

1/4 1/4 1/4 1/4

1/4

1/4

1/4

1/4

BbEe BbEe

BE

BE

bE

bE

Be

Be

be

be

BBEE BbEE BBEe BbEe

BbEE bbEE BbEe bbEe

BBEe BbEe BBee Bbee

BbEe bbEe Bbee bbee

Polygenic Inheritance • Polygenic inheritance is the additive effect of

two or more genes on a phenotype

• Polygenic inheritance results in quantitative traits, traits which vary along wide a spectrum

• Human skin color is a result of polygenic inheritance

Figure 14.13

Eggs

Sperm

Phenotypes:

Number of dark-skin alleles: 0 1 2 3 4 5 6

1/8 1/8 1/8 1/8 1/8 1/8 1/8 1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/8

1/64 6/64 15/64 20/64 15/64 6/64 1/64

AaBbCc AaBbCc

The Environmental Impact on Phenotype

• Nature vs. Nuture

• Phenotype can depend on the environment

• For example, hydrangea flowers of the same genotype range from blue-violet to pink, depending on soil acidity

Twin Studies • Two identical twins separated at birth are later

reunited and compared

• Twin studies attempt to distinguish between genetic and environmental causes

Epigenetics

• The study of heritable changes in phenotype caused by something other than a change in the underlying DNA sequence

• Environmental triggers may cause these epigenetic changes

– In mice, exposure to bisphenol A in the womb causes the growth of yellow fur and obesity

Multifactorial traits

• Multifactorial traits are those caused a combination of genetics and environment

– Heart disease, cancer, obesity

• It is very difficult to tease out exactly how much of a trait is caused by a gene, and how much by the environment

Expanding our idea of a phenotype

• An organism’s phenotype includes its physical appearance, internal anatomy, physiology, and behavior

• An organism’s phenotype reflects its overall genotype and unique environmental history

• Your genes are not your destiny

Mendelian genetics still applies to humans

• ….Sometimes

• Many genetic disorders are inherited in a recessive manner

• These range from relatively mild to life-threatening

Recessive alleles and diseases

• Recessively inherited disorders show up only in individuals homozygous for the allele

• Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with recessive disorders are born to carrier parents

• Albinism is a recessive condition characterized by a lack of pigmentation in skin and hair

Albinism is a recessive disorder

Parents

Normal Aa

Sperm

Eggs

Normal Aa

AA Normal

Aa Normal (carrier)

Aa Normal (carrier)

aa Albino

A

A

a

a

Recessive alleles and diseases • If a recessive allele that causes a disease is rare,

then the chance of two carriers meeting and mating is low

• Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele

• Most societies and cultures have laws or taboos against marriages between close relatives

Inbreeding • The royal family of Spain inbred for

generations

• Prince Charles II:

Dominant Alleles and Diseases

• Some human disorders are caused by dominant alleles

• Dominant alleles that cause a lethal disease are rare because they breed themselves out of the population

• They often arise by mutation

• Achondroplasia is a form of dwarfism caused by a rare dominant allele

Achondroplasia

• Tyrion

Huntington’s Disease

• The timing of onset of a disease significantly affects its inheritance

• Huntington’s disease is a dominant, degenerative disease of the nervous system

• The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age

• Once the deterioration of the nervous system begins the condition is irreversible and fatal

Huntington’s Disease • Length of repeats in the Htt gene determines

if and when the disease will strike

• Exact mechanism of pathogenesis not known

Cystic Fibrosis

• The most common lethal genetic disease in the United States, striking one out of every 2,500 people of European descent

• The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes leading to a buildup of chloride ions outside the cell

• Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine

Cystic Fibrosis • Body produces abnormally thick and sticky mucus

that builds up in the lungs

• A transport protein responsible for regulating sodium and chloride transport across cell membranes is defective

• 1 in 25 Caucasians is a carrier

• No cure except lung transplant

Sickle Cell Anemia

• Sickle-cell disease affects one out of 400 African-Americans

• The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells

• In homozygous individuals, all hemoglobin is abnormal (sickle-cell)

• Symptoms include physical weakness, pain, organ damage, and even paralysis

Sickle Cell Anemia

• Heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer some symptoms

• About one out of ten African Americans has sickle cell trait, an unusually high frequency of an allele with detrimental effects in homozygotes

• Heterozygotes are less susceptible to the malaria parasite, so there is an advantage to being heterozygous

Sickle Cell Anemia

• The malaria parasite is relatively big, and has trouble entering sickle-shaped cells

Genetic Testing and Counseling

• Genetic tests exist that can identify carriers of a disease allele

• Genetic counselors can then work with the person to identify their best course of action

• Testing can also be done on fetuses to determine if any genetic abnormalities are present

At-Home Genetic Tests

• Some companies are offering genetic tests you can take at home

• These tests cannot tell you anything truly useful yet

Genetics Problems Genetics problems will ask you to predict the

genotypes/phenotypes of the offspring given the genotypes/phenotypes of the parents

Constructing Punnet Squares lets you predict the outcome of a cross between two parents

They show every possible genotype and phenotype between one maternal

allele and one paternal allele

Why do Punnet Squares?

• They allow you to estimate the probabilities of seeing certain traits in subsequent generations

• However, they have their limits

– Few human traits follow simple dominant/recessive patterns

Types of Punnet Squares

• Monohybrid crosses

– Involve one gene

• Dihybrid crosses

– Involve two genes

• Trihybrid crosses

– Involve three genes

Monohybrid cross

AA x aa 1. Determine your gametes. Remember, the genotypes given above are for diploids. Gametes are haploid, and so will have only one allele (law of segregation)

Gametes for AA: A and A Gametes for aa: a and a

Homozygous dominant Homozygous recessive

Aa Aa

Aa Aa

2. Arrange your gametes across the side and top of the square

A A

a a

3. Combine your gametes into your new offspring

Monohybrid cross

AA x aa Homozygous dominant Homozygous recessive

Aa Aa

Aa Aa

A A

a a

4. Write out your new genotype and phenotype ratios

Genotype ratio 1:1:1:1 Aa (No phenotypes were given)

Monohybrid cross

EE eE

Ee ee

E e

E e

A man who is heterozygous for attached earlobes has children with a woman who is also heterozygous for attached earlobes. What are the possible genotypes and phenotypes of their children? Attached earlobes are a dominant trait.

1. Choose the letter you want to represent for earlobe attachment 2. Determine the genotypes of the parents 3. Determine the gametes of the parents 4. Write out your Punnet Square

Ee x Ee Man Heterozygous

Woman Heterozygous

Genotype ratio: 1:2:1, EE:Ee:ee Phenotype ratio: 3:1, attached earlobe: free earlobe

Dihybrid cross AaBb x AaBb

1. Determine your gametes

Gametes for AaBb: AB, Ab, aB, ab Gametes for AaBB: AB, Ab, aB, ab

2. Write out your Punnet Square and arrange the gametes across the top and side

AABB AABb AaBB AaBb

AABb AAbb AaBb Aabb

AaBB AaBb aaBB aaBb

AaBb Aabb aaBb aabb

AB Ab aB ab

AB

Ab

aB ab

Genotype ratio: 1:2:1:2:4:2:1:2:1 Phenotype ratio: 9:3:3:1

Codominance

Heterozygote Type A Heterozygote Type B

IAIB IA i

IBi ii

IB i

IA i

4. Write out your new genotype and phenotype ratios

Genotype ratio 1:1:1:1, IA IB : IA i : IB i: ii

Phenotype ratio: 1:1:1:1 Type AB: Type A: Type B, Type O

A heterozygote for blood type A is crossed with a heterozygote for blood type B. What are the possible genotype and phenotype ratios of their children?

IAi x IBi

Epistasis Two Labrador retrievers that are heterozygous for two genes are crossed. These two genes control pigment depositing and coat color. Without a functional copy of the pigment depositing gene, the color will not be expressed regardless of whether it is brown or black.

For example, in Labrador retrievers and many other mammals, coat color depends on two genes

One gene determines the pigment color (with alleles B for

black and b for brown). Black is the dominant color.

The other gene (with alleles E for color and e for no color) determines whether the pigment will be deposited in the

hair. Color depositing is the dominant trait.

Epistasis is by necessity a dihybrid cross!

Epistasis

9 : 3 : 4

BbEe BbEe

BE

BE

bE

bE

Be

Be

be

be

BBEE BbEE BBEe BbEe

BbEE bbEE BbEe bbEe

BBEe BbEe BBee Bbee

BbEe bbEe Bbee bbee

Sex-linked traits

Non-colorblind man Colorblind woman

XNXn XnY

XNXn XnY

XN Y

Xn

Xn

4. Write out your new genotype and phenotype ratios

Genotype ratio 2:2, XNXn : XnY

Phenotype ratio: 2:2 normal female: colorblind male

The trait for red-green colorblindness is sex-linked. Normal vision is dominant to colorblindness. A normal-visioned man, whose father had red-green colorblindness, marries a red-green colorblind woman.

XNY x XnXn

Practice Problems

• http://biology.clc.uc.edu/courses/bio105/geneprob.htm

Highly recommended!!!

Further Links

• Online Mendelian Inheritance in Man – the premier database on Mendelian genetic disorders – http://www.ncbi.nlm.nih.gov/omim

• How MC1R causes red hair – http://ghr.nlm.nih.gov/gene/MC1R

• More on how dominant alleles can be dominant – http://www.thetech.org/genetics/ask.php?id=227

Further links

• More on epigenetics – http://learn.genetics.utah.edu/content/epigenetic

s/

• More on incomplete vs. codominance – http://www.hobart.k12.in.us/jkousen/Biology/inc

codom.htm

• More on polydactyl cats – http://www.messybeast.com/poly-

cats.html#genes

Vocabulary • Parental, F1, F2 generation • Test cross • Genome, chromosome, gene, nucleotide • Dominant, recessive • Genotype, phenotype • Pleiotropy • Complete dominance • Incomplete dominance • Codominance • Epistasis • Polygenic inheritance • Quantitative characteristics