Chapter 4

Genetics and
Cellular Function

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DNA Structure and Function

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Purines
O

Nucleotides

NH2
C

Sugar, phosphate, nitrogenous base

C
C
H

Complementary base pairing

N
C

CH

HN

NH

NH

C
C

CH

NH2

Adenine (A)

Guanine (G)

Pyrimidines

H
C

Antiparallel

NH2

CH3

HC

C
N

N
H

O
C

HC

NH
N
H

Cytosine (C)

C
O

Thymine (T)
O

HN
C
O
(b)

N
H

CH
CH Uracil (U)

Figure 4.1b

4-2

Chromatin and Chromosomes

Kinetochore

Centromere

Sister
chromatids

Figure 4.4b

4-3

(a)

Figure 4.5a

4-3

RNA Structure and Function

Ribonucleic acids (RNAs)
Smaller molecules that resemble DNA
Can have less than 100 or just over 10,000 bases per
molecule

Three important RNAs for protein synthesis

Messenger RNA (mRNA)
Ribosomal RNA (rRNA)
Transfer RNA (tRNA)

4-4

RNA Structure and Function

4-5

What Is a Gene?
Previous definition: genea segment of DNA that
carries the code for a particular protein
But body has millions of proteins and only about 20,000 genes

Current definition: genean information-containing

segment of DNA that codes for the production of a
molecule of RNA that plays a role in synthesizing one or
more proteins
Amino acid sequence of a protein is determined by the
nucleotide sequence in the DNA

4-6

The Genetic Code

Base tripleta sequence of three DNA
nucleotides that stands for one amino acid
Codonthe 3-base sequence in mRNA
64 possible codons available to represent the 20
amino acids
61 code for amino acids; 3 are stop codons
Stop codonsUAG, UGA, and UAA: signal end of
message, like a period at the end of a sentence
Start codonAUG codes for methionine, and begins the
amino acid sequence of the protein

4-7

Protein Synthesis
When a gene is activated, messenger RNA
(mRNA) is made
mRNAcomplementary to gene
Migrates from the nucleus to cytoplasm where it codes for amino
acids

Process of protein synthesis

DNA
mRNA
protein
In transcription, DNA codes for mRNA
Occurs within nucleus

In translation, mRNA codes for protein

Usually occurs in cytoplasm
4-8

Transcription
Copying DNA into mRNA
RNA polymerase
Certain DNA base sequences signal start (e.g., TATATA)
RNA polymerase opens up the DNA helix and reads
bases from one strand of DNA
Makes corresponding mRNA
RNA polymerase rewinds the DNA helix behind it
Terminator sequence

RNA Processing

4-9

Alternative Splicing of mRNA

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Gene (DNA)

1 Transcription
Intron Exon

Pre-mRN
A
A

2 Splicing
mRNA 1
A

mRNA 2
D

mRNA 3
E

3 Translation
Protein 1

Protein 2

Protein 3

Figure 4.6

One gene can code for more than one protein

Exons can be spliced together into a variety of
different mRNAs

4-10

Translation
Converts the language of nucleotides into the
language of amino acids
Three main participants in translation
mRNA
Transfer RNA (tRNA)
Ribosomes

Three steps
Initiation
Elongation
Termination

4-11

Translation
Initiation
mRNA binds to small ribosomal subunit
Initiator tRNA pairs with start codon (first AUG)
Large ribosomal subunit joins the complex and reads bases

Elongation

Next charged tRNA binds to ribosome

Peptide bond forms between methionine and second amino acid peptidyltransferase
Ribosome slides to read next codon and releases uncharged initiator tRNA
Next charged tRNA binds to ribosome
Peptide bond forms (between 2nd and 3rd amino acids)
Process repeats

Termination
When ribosome reaches stop codon, a release factor binds
Finished protein breaks away from ribosome
Ribosome dissociates into two subunits

4-12

Translation

Translation can be rapid

Figure 4.9

Polyribosomeone mRNA attached to multiple ribosomes (commonly

10-20 ribosomes at once)

Cell may have 300,000 identical mRNA molecules undergoing

simultaneous translation
Cell can produce over 100,000 protein molecules per second

4-13

Translation
After translation, some proteins are packaged
and some are exported
Proteins headed for lysosomes or for secretion
are made on ribosomes on the rough ER
Newly made protein is threaded into rough ER where
it is modified and packaged into a transport vesicle

4-14

Review of Peptide Formation

Figure 4.10

4-15

Protein Processing and Secretion

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Protein formed by
ribosomes on rough ER.
2 Protein packaged into transport
vesicle, which buds from ER.

Nucleus

3 Transport vesicles fuse into clusters that

unload protein into Golgi complex.
4 Golgi complex modifies
protein structure.
5 Golgi vesicle containing
finished protein is formed.
6 Secretory vesicles
release protein by
exocytosis.

Ribosomes
Clathrin-coated
transport vesicle

Golgi
complex

Rough ER

Lysosome

Figure 4.11
4-16

Gene Regulation
Genes can be turned on and off
Cells can turn some genes permanently off
Example: liver cells turn off hemoglobin genes

Cells can turn genes on only when needed

The level of gene expression can vary from day to day
or hour to hour
This can be controlled by chemical messengers such
as hormones
Example: mammary gland cells turn on gene for casein
protein only when breast milk is produced

4-17

Gene Regulation
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Prolactin
Prolactin
receptor

Casein

Exocytosis

ATP

Secretory
vesicles

ADP
+
Pi

6
Golgi
complex

Regulatory
protein
(transcription
activator)

Rough
endoplasmic
reticulum
5

3
4

Casein
gene

mRNA
for casein

RNA
polymerase

Figure 4.12
4-18

DNA Replication
Semi-conservative, bi-directional
Enzymes

Helicase
RNA Primase
DNA Polymerase III
DNA Polymerase I
Ligase

4-19

DNA Replication

Figure 4.14
4-20

Errors and Mutations

DNA polymerase does make mistakes
Proofreading
Result is only one error per 1 billion bases replicated

Mutationschanges in DNA structure due to

replication errors or environmental factors
(radiation, viruses, chemicals)
Some mutations cause no ill effects, others kill the cell,
turn it cancerous, or cause genetic defects in future
generations

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The Cell Cycle

Cell cyclecells life from
one division to the next
Interphase includes three
subphases
G1, S, G2

Mitotic phase includes

multiple subphases
Prophase, Metaphase,
Anaphase, Telophase

Figure 4.15

4-22

Mitosis

Figure 4.16 parts 1 & 2

4-23

Mitosis

Figure 4.16 parts 3 & 4

4-24

Mitosis
Cytokinesisdivision of cytoplasm into two
cells
Telophase is the end of nuclear division but overlaps
cytokinesis

Achieved by myosin protein pulling on actin in

the terminal web of cytoskeleton
Creates cleavage furrow around the equator
of cell
Cell eventually pinches in two

4-25

The Timing of Cell Division

Cells divide when:

They have enough cytoplasm for two daughter cells

They have replicated their DNA
They have adequate supply of nutrients
They are stimulated by growth factors (chemical signals)
Neighboring cells die, opening up space

Cells stop dividing when:

They snugly contact neighboring cells
Nutrients or growth factors are withdrawn
They undergo contact inhibitionthe cessation of cell
division in response to contact with other cells
4-26

Chromosomes and Heredity

Hereditytransmission of
genetic characteristics from
parent to offspring
Karyotypechart of 46
chromosomes laid out in
order by size
23 pairsthe two members of
each pair are called
homologous chromosomes
Autosomes
Sex chromosomes

Diploid vs haploid
4-27

Genes and Alleles

Locusthe location of a particular gene on a
chromosome
Allelesdifferent forms of gene at same locus on
two homologous chromosomes
Dominant
Recessive

Genotype
Phenotype
Punnet squarediagram showing possible
genotype and phenotype outcomes from parents of
known genotype
4-28

Genetics of Cleft Chin

Allele for cleft chin is

dominant
Parents are heterozygous
Each parent has cleft chin
phenotype
One out of four offspring
will have uncleft chin

Figure 4.18 b
4-29

Multiple Alleles, Codominance, and

Incomplete Dominance
Multiple allelesmore than two allelic forms of gene
Example: three alleles for ABO blood types
IA, IB, i alleles for ABO blood types

Codominanceboth alleles equally dominant

Both are phenotypically expressed
Example: IAIB = type AB blood

Incomplete dominance
Heterozygous individual shows phenotype intermediate
between traits each allele would have produced alone
Example: familial hypercholesterolemia
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Polygenic Inheritance

Figure 4.19

Polygenic inheritancegenes at two or more loci

contribute to a single phenotypic trait
Examples: eye color, skin color, some forms of cancer

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Pleiotropy

Figure 4.20

Pleiotropyone gene produces multiple phenotypic effects

Example: alkaptonuriadisorder resulting from mutation on
chromosome 3 that blocks the breakdown of tyrosine
4-32

Sex Linkage
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

X
Female (XX)
Genotype Cc
Normal vision

Male (XY)
Genotype c
Color blindness

Figure 4.21

Sex-linked traitscarried on X or Y chromosome, and

therefore tend to be inherited by one sex more than the other
Recessive color blindness allele on X, no gene locus for
trait on Y, so color blindness more common in men (mother
is carrier in illustrated example)

4-33

Environmental Effects

Example: genes for melanin

eye pigment can only be fully
expressed if phenylalanine is in
diet

Phenylalanine
(amino acid)

Tyrosine

Enzyme 1

Melanin
(pigment)

Enzyme 2

From diet
(environment)

Phenotype
(brown eyes)
mRNA 1
Genes
(DNA)

mRNA 2

Figure 4.22
4-34

Dominant and Recessive Alleles at

the Population Level
Common misconception that dominant alleles
must be more common in the gene pool than
recessive alleles
Some recessive alleles, blood type O, are the
most common
Some dominant alleles, polydactyly and blood
type AB, are rare in the population

4-35

Epigenetics
Examines nongenetic changes that alter gene
expression and can be passed to offspring
Gene expression is changed without genetic mutation to
base sequence
DNA methylationmechanism of epigenetic change in
which methyl groups are added to DNA
Often silences the gene
Inappropriate DNA methylation implicated in some forms of
cancer

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Cancer
Malignant tumors cause
cancer
Fast growing, tend to
metastasizeto give off
cells that spread and seed
the growth of tumors
elsewhere
Distinguished from slow
growing, encapsulated
benign tumors

Figure 4.23
4-37

Cancer
Oncologymedical specialty dealing with tumors
Tumor angiogenesisgrowth of blood vessels by
energy-hungry tumors
Cancers are named for tissue of origin

Carcinomas: in epithelial tissue

Lymphomas: in lymph nodes
Melanomas: in pigment cells of epidermis (melanocytes)
Leukemias: in blood-forming tissues
Sarcomas: in bone, other connective tissue, or muscle

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Cancer
Carcinogensenvironmental cancer-causing
agents
Radiationultraviolet rays, X-rays
Chemicalcigarette tar, food preservatives, industrial
chemicals
Viruseshuman papillomavirus, hepatitis C, and type 2
herpes simplex

Only 5% to 10% of cancers are hereditary

Carcinogens trigger gene mutations
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Cancer
Oncogenes
Cause cell division to accelerate out of control
Excessive production of growth factors or growth-factor receptors
that stimulate mitosis

Tumor-suppressor (TS) genes

Healthy tumor suppressor genes inhibit development of
cancer
Some code for DNA-repair enzymes

Mutated TS genes or silenced TS genes leave oncogene

action unopposed

4-40

Cancer
Wilms tumor
Malignant tumor of
the kidney occurring
especially in children

Figure 4.24
4-41

Lethal Effects of Cancer

Replace functional tissue in vital organs
Often invade blood vessels, lung tissue, or brain tissue

Steal nutrients from the rest of the body

Cachexia: severe wasting away of depleted tissues

Weaken ones immunity

Open the door for opportunistic infections

4-42