Transcript Chapter 25: Molecular Basis of Inheritance

Nucleic Acids and Genetics
A Language of Its Own
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DNA Structure and Replication
In the mid-1900s, scientists knew that
chromosomes, made up of DNA
(deoxyribonucleic acid) and proteins,
contained genetic information.
However, they did not know whether the
DNA or the proteins was the actual
genetic material.
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Various reseachers showed that DNA
was the genetic material when they
performed an experiment with a T2
virus.
By using different radioactively labeled
components, they demonstrated that
only the virus DNA entered a bacterium
to take over the cell and produce new
viruses.
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Viral DNA is labeled
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Viral capsid is labeled
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The Structure of DNA
In the early 1950s, Rosalind Franklin and her
associates began to test X-ray beams with DNA. The
X-ray scattering produces a pattern that provides
important clues to the structure of many molecules.
This X-ray diffraction
photograph of DNA was
taken by Franklin. The Xshaped pattern in the center
indicates that the structure
of DNA is helical.
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Structure of DNA
The structure of DNA was determined by
James Watson and Francis Crick in the
early 1950s.
DNA is a polynucleotide; nucleotides are
composed of a phosphate, a sugar, and
a nitrogen-containing base.
DNA has the sugar deoxyribose and four
different bases: adenine (A), thymine
(T), guanine (G), and cytosine (C).
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One pair of bases
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Watson and Crick showed that DNA is a
double helix in which A is paired with T
and G is paired with C.
This is called complementary base pairing
because a purine (A and G) is always
paired with a pyrimidine (T and C).
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When the DNA double helix unwinds, it
resembles a ladder.
The sides of the ladder are the sugarphosphate backbones, and the rungs of
the ladder are the complementary
paired bases.
The two DNA strands are anti-parallel –
they run in opposite directions.
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DNA double helix
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Replication of DNA
DNA replication occurs during
chromosome duplication; an exact copy
of the DNA is produced with the aid of
DNA polymerase.
Hydrogen bonds between bases break
and enzymes “unzip” the molecule.
Each old strand of nucleotides serves as
a template for each new strand.
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New nucleotides move into
complementary positions are joined by
DNA polymerase.
The process is semiconservative
because each new double helix is
composed of an old strand of
nucleotides from the parent molecule
and one newly-formed strand.
Some cancer treatments are aimed at
stopping DNA replication in rapidlydividing cancer cells.
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Overview of DNA replication
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Ladder configuration and DNA
replication
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RNA
RNA (ribonucleic acid) is a singlestranded nucleic acid in which A pairs
with U (uracil) while G pairs with C.
Three types of RNA are involved in gene
expression: messenger RNA (mRNA)
carries genetic information to the
ribosomes, ribosomal RNA (rRNA) is
found in the ribosomes, and transfer
RNA (tRNA) transfers amino acids to
the ribosomes, where the protein
product is synthesized.
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Structure of RNA
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Two processes are involved in the
synthesis of proteins in the cell:
Transcription makes an RNA molecule
complementary to a portion of DNA.
Translation occurs when the sequence of
bases of mRNA directs the sequence of
amino acids in a polypeptide.
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The Genetic Code
DNA specifies the synthesis of proteins
because it contains a triplet code: every
three bases stand for one amino acid.
Each three-letter unit of an mRNA
molecule is called a codon.
Most amino acids have more than one
codon; there are 20 amino acids with a
possible 64 different triplets.
The code is nearly universal among living
organisms.
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Messenger RNA codons
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Central Concept
The central concept of genetics involves
the DNA-to-protein sequence involving
transcription and translation.
DNA has a sequence of bases that is
transcribed into a sequence of bases in
mRNA.
Every three bases is a codon that stands
for a particular amino acid.
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Overview of gene expression
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Transcription
During transcription in the nucleus, a
segment of DNA unwinds and unzips,
and the DNA serves as a template for
mRNA formation.
RNA polymerase joins the RNA
nucleotides so that the codons in
mRNA are complementary to the triplet
code in DNA.
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Transcription and mRNA synthesis
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Translation
Translation is the second step by which
gene expression leads to protein
synthesis.
During translation, the sequence of
codons in mRNA specifies the order of
amino acids in a protein.
Translation requires several enzymes
and two other types of RNA: transfer
RNA and ribosomal RNA.
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Transfer RNA
During translation, transfer RNA (tRNA)
molecules attach to their own particular
amino acid and travel to a ribosome.
Through complementary base pairing
between anticodons of tRNA and
codons of mRNA, the sequence of
tRNAs and their amino acids form the
sequence of the polypeptide.
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Transfer RNA: amino acid carrier
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Ribosomal RNA
Ribosomal RNA, also called structural
RNA, is made in the nucleolus.
Proteins made in the cytoplasm move
into the nucleus and join with
ribosomal RNA to form the subunits of
ribosomes.
A large subunit and small subunit of a
ribosome leave the nucleus and join in
the cytoplasm to form a ribosome just
prior to protein synthesis.
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A ribosome has a binding site for mRNA
as well as binding sites for two tRNA
molecules at a time.
As the ribosome moves down the mRNA
molecule, new tRNAs arrive, and a
polypeptide forms and grows longer.
Translation terminates once the
polypeptide is fully formed; the
ribosome separates into two subunits
and falls off the mRNA.
Several ribosomes may attach and
translate the same mRNA, therefore the
name polyribosome.
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Polyribosome structure and
function
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Review of Gene Expression
DNA in the nucleus contains a triplet
code; each group of three bases stands
for one amino acid.
During transcription, an mRNA copy of
the DNA template is made.
The mRNA is processed before leaving
the nucleus.
The mRNA joins with a ribosome, where
tRNA carries the amino acids into
position during translation.
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Gene expression
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Gene Mutations
A gene mutation is a change in the
sequence of bases within a gene.
Frameshift Mutations
Frameshift mutations involve the addition
or removal of a base during the
formation of mRNA; these change the
genetic message by shifting the
“reading frame.”
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Point Mutations
The change of just one nucleotide
causing a codon change can cause the
wrong amino acid to be inserted in a
polypeptide; this is a point mutation.
In a silent mutation, the change in the
codon results in the same amino acid.
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If a codon is changed to a stop codon,
the resulting protein may be too short
to function; this is a nonsense
mutation.
If a point mutation involves the
substitution of a different amino acid,
the result may be a protein that cannot
reach its final shape; this is a missense
mutation.
An example is Hbs which causes sicklecell disease.
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Sickle-cell disease in humans
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Cause and Repair of Mutations
Mutations can be spontaneous or caused
by environmental influences called
mutagens.
Mutagens include radiation (X-rays, UV
radiation), and organic chemicals (in
cigarette smoke and pesticides).
DNA polymerase proofreads the new
strand against the old strand and detects
mismatched pairs, reducing mistakes to
one in a billion nucleotide pairs
replicated.
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Cancer: A Failure of Genetic
Control
Cancer is a genetic disorder resulting in
a tumor, an abnormal mass of cells.
Carcinogenesis, the development of
cancer, is a gradual process.
Cancer cells lack differentiation, form
tumors, undergo angiogenesis and
metastasize.
Cancer cells fail to undergo apoptosis, or
programmed cell death.
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Cancer cells
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Origin of Cancer
Mutations in at least four classes of
genes are associated with the
development of cancer.
1) The nucleus has a DNA repair system
but mutations in genes for repair
enzymes can contribute to cancer.
2) Mutations in genes that code for
proteins regulating structure of
chromatin can promote cancer.
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3) Proto-oncogenes are normal genes
that stimulate the cell cycle and tumorsuppressor genes inhibit the cell cycle;
mutations can prevent normal
regulation of the cell cycle.
4) Telomeres are DNA segments at the
ends of chromosomes that normally
get shorter and signal an end to cell
division; cancer cells have an enzyme
that keeps telomeres long.
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Causes of cancer
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Chapter Summary
Since DNA is the genetic material, its
structure and functions constitute the
molecular basis of inheritance.
Because the DNA molecule is able to
replicate, genetic information can be
passed from one cell generation to the
next.
DNA codes for the synthesis of proteins;
this process also involves RNA.
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In eukaryotes, the control of gene
expression occurs at all stages, from
transcription to the activity of proteins.
Gene mutations vary; some have little
effect but some have a dramatic effect.
Loss of genetic control over genes
involved in cell growth and/or cell
division cause cancer.
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