V. Gene Expression II V.

Gene Expression II

If each cell has the same DNA, how do we get all DNA packing helps to regulate
of the different cells in our bodies? gene expression

Muscle cells
Nerve cells Bone cells •Some regions of our DNA remain
highly condensed even during
interphase

• This highly condensed DNA is

unavailble for transcription, and
therefore genes in these regions
are not expressed

Differentiation: cells become specialized. Results • This is one way for cells to
from selective gene expression—the turning on and regulate which genes will be
turning off of specific genes turned on or off

V. Gene Expression II

DNA Mutations

Multiple mechanisms regulate I. Definition and Frequency

gene expression in eukaryotes II. Types of Mutations
III. DNA Proofreading and Repair
IV. Mutations and Cancer

I. Definition and Frequency I. Definition and Frequency

Mutations are changes in the DNA base
sequence caused by errors in DNA replication or A. Mutations in the body cells
recombination, or by mutagens Æ Can cause serious health problems for the
individual (e.g. cancer)
Æ Are not passed on to offspring

B. Mutations in the gametes

Æ Can be passed on from parent to offspring

Mistakes could happen:

• during DNA replication
• spontaneously
• from exposure to chemicals and/or radiation
Mutations can change the meaning of genes

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II. Types of Mutations II. Types of Mutations
A) Point Mutations
A) point mutation: nucleotide substitution
Result from alterations in single base pairs of DNA
Æ Silent mutations Wild type allele
• No change to AA (redundancy of code) AA sequence M D D Q S R M L Q T L A G
Æ Missense mutations nucleotide seq. atg gac gat caa tcc agg atg ctg cag act ctg gcc ggg
• Change in AA sequence
Æ Nonsense mutation Silent point mutation
AA sequence M D D Q S R M L Q T L A G
• Causes stop codon to form in middle (nonfunctional) nucleotide seq. atg gac gat caa tcc agg atg ctg caa act ctg gcc ggg
B) Insertions/Deletions (Indels)
Missense point mutation
Result from the addition or deletion of single or multiple base pairs AA sequence M D D Q S R M L K T L A G
nucleotide seq. atg gac gat caa tcc agg atg ctg aag act ctg gcc ggg
Æ Could result in a Frameshift mutation
• insertion or deletion alters the reading frame
Nonsense point mutation
C) Chromosomal Alteration AA sequence M D D Q S R M L stop
nucleotide seq. atg gac gat caa tcc agg atg ctg tag act ctg gcc ggg
Result from broad changes in gene position
Æ Could alter the rate of transcription (e.g. proximity to a promoter,
location in heterochromatin)

B) insertion: addition of one or more nucleotides C) deletion: loss of one or more nucleotides
Wild type allele
AA sequence M D D Q S R M L Q T L A G
nucleotide seq. atg gac gat caa tcc agg atg ctg cag act ctg gcc ggg

3-base pair addition, EX 1 Wild type allele

AA sequence M D D Q S R M L Q T D L A G AA sequence M D D Q S R M L Q T L A G
nucleotide seq. atg gac gat caa tcc agg atg ctg cag act gac ctg gcc ggg nucleotide seq. atg gac gat caa tcc agg atg ctg cag act ctg gcc ggg

3-base pair addition, EX 2 3 base-pair deletion

AA sequence M D D H Q S R M L Q T L A G AA sequence M D D Q S R M L T L A G
nucleotide seq. atg gac gat cac caa tcc agg atg ctg cag act ctg gcc ggg nucleotide seq. atg gac gat caa tcc agg atg ctg act ctg gcc ggg

2-base pair addition causing a frameshift 1 base pair deletion in the start codon
AA sequence M D D Q N P G C C R L W P … AA sequence NO TRANSLATION
nucleotide seq. atg gac gat caa aat cca gga tgc tgc aga ctc tgg ccg gg nucleotide seq. agg acg atc aat cca gga tgc tgc aga ctc tgg ccg gg

Effects of Insertions and Deletions

D) chromosomal alteration: change in gene position

Cri du chat
Chromosome 5 deletion
1 in 25,000-50,000
Detected by amniocentesis
Mental retardation
May live normal life span

Huntington’s Disease
Results from the insertion of a repeated trinucleotide motif

ATT GAC TAG CAG CAG CAG CAG CAG CAG … CAG CAG CAG TAT

CAG codes for glutamine; the repeated motif changes the structure of
the protein

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IV. Mutations and Cancer IV. Mutations and Cancer
Cancer: a class of diseases characterized by uncontrolled Carcinoma of the lung
cell division and the ability of these cells to invade other
tissues; unrestrained cell proliferation

This can occur by:

1. direct growth into adjacent tissue (invasion), or
Connective
2. migration of cells to distant sites through the tissue
blood stream (metastasis) Blood
vessel
This unregulated growth is caused by a series of acquired Lymphatic
or inherited mutations to DNA within cells that damage cells vessel
regulating the cell division cycle Smooth
muscle
Can be caused by: chemicals, viruses, UV & inherited genes Metastatic cells Blood vessel

Cancer in the United States IV. Mutations and Cancer

Cancer Carcinogens Cases in
1999

Prostate Testosterone; dietary fat 179,300

Breast Estrogen; possibly dietary fat 176,300

Lung Cigarette smoke 171,600

Colon & Rectum High dietary fat; low dietary fiber 129,400

Bladder Cigarette smoke 54,200

Skin Ultraviolet light 44,200

Kidney Cigarette smoke 30,000

Mouth and Throat Tobacco & alcohol 29,800

Pancreas Cigarette smoke 28,600

Stomach Table salt; cigarette smoke 21,900

Multiple mutations are required in order for cells to
Cervix Viruses; cigarette smoke 12,800 become cancerous. Some of the mutations can be
inherited, others can be acquired.