bio Lecture 12: Part 2 - The Structure and Function of DNA

Mutations Any change in

the nucleotides sequence of a cell’s DNA

Mutations can involve

large regions of a chromosome or just a single nucleotide pair, as in sickle-cell disease

Occasionally, a base substitution leads to an improved protein or one with new capabilities that enhance the success of the mutant organism and its descendants

• Much more often

mutations are harmful

Mutations within a gene can be divided into two general categories:

1. Nucleotide Substitutions and

2. Nucleotide Insertions or Deletions

A substitution is the replacement of one

nucleotide and its base-pairing partner with another pair

Because the genetic code is redundant, some substitution mutations have no effect at all:

if a mutation causes an mRNA codon to change from GAA to GAG, no change in the protein product would result because GAA and GAG both code for the same amino acid (Glu)

Such a change is called a silent mutation

types of mutations

substitution

insertion

deletion

inversion

Other substitutions involving a single nucleotide do change the amino acid coding

Such mutations are called missense mutations

if a mutation causes an mRNA codon to change from GGC to AGC, the resulting

protein will have a serine (Ser) instead of a glycine (Gly) at this position

Some missense mutations have

little or no effect on the shape or function of the resulting protein

Some substitutions, called nonsense mutations,

change an amino acid codon into a stop codon. For example, if an AGA (Arg) codon is mutated to a UGA (stop) codon, the result will be a prematurely terminated protein, which probably will not function properly

Mutations involving the deletion or insertion of one or more nucleotides in a gene, called

frameshift mutations, often have disastrous effects

Because mRNA is read as a series of nucleotide

triplets during translation, adding or subtracting nucleotides may alter the triplet grouping of the genetic message

All the nucleotides after the insertion or deletion will be

regrouped into different codons

Similarly, a frameshift mutation most

often produces a nonfunctioning polypeptide

Other sources of mutation are physical and chemical

agents called mutagens

The most common physical mutagen is

high-energy radiation, such as X-rays and ultraviolet (UV) light

Chemical mutagens are of various types. One type, for example

consists of chemicals that are similar to normal DNA bases but that base-pair incorrectly when incorporated into DNA

many mutagens can act as

carcinogens, agents that cause cancer

A virus is an infectious particle consisting of

nucleic acid wrapped in a protein coat and, in some cases, an envelope of membrane

A virus is generally not considered alive because it is

not cellular and cannot reproduce on its own

Viruses share some of the characteristics of living organisms, such as having

genetic material in the form of nucleic acid

A virus can multiply only by

infecting a living cell and directing the cell’s molecular machinery to make more viruses

Viruses that attack bacteria are called

bacteriophages, or phages for short

The phage consists of a molecule of DNA

enclosed within an elaborate structure made of proteins

The “legs” of the phage bend when they

touch the cell surface

Bacteriophages The tail is a

hollow rod enclosed in a spring-like sheath

Bacteriophages As the legs bend

the spring compresses, the bottom of the rod punctures the cell membrane, and the viral DNA passes from inside the head of the virus into the cell

Bacteriophages Once they infect a bacterium, most phages

enter a reproductive cycle called the lytic cycle

The lytic cycle gets its name from the fact that after many copies of the phage are produced within the bacterial cell,

the bacterium lyses (breaks open)

Some viruses can also reproduce by an alternative route

the lysogenic cycle

During a lysogenic cycle

viral DNA replication occurs without phage production or the death of the cell

At the start of infection, lambda

binds to the outside of a bacterium and injects its DNA inside

The injected lambda DNA forms a circle. In the lytic cycle, this DNA

immediately turns the cell into a virus-producing factory

The bacteria cell’s own machinery for DNA replication, transcription, and translation is

hijacked by the virus and used to produce copies of the virus. The cell lyses, releasing the new phages

In the lysogenic cycle, the viral DNA is inserted into the

bacterial chromosome

into the bacterial chromosome. Once there, the phage DNA is

referred to as a prophage, and most of its genes are inactive

A single infected bacterium can quickly give rise to a large population of bacteria that

all carry prophages

The prophages may remain in the bacterial cells

indefinitely

Occasionally, however, a prophage leaves its chromosome;

this event may be triggered by environmental conditions such as exposure to a mutagen. Once separate, the lambda DNA usually switches to the lytic cycle, which results in the production of many copies of the virus and lysing of the host cell

Viruses that infect animal cells are a

common causes of disease

No virus is a greater human health threat than the

influenza (flu) virus

influenza (flu) virus Like many animal viruses, this one has

an outer envelope made of phospholipid membrane, with projecting spikes of protein

influenza phospholipid membrane, with projecting spikes of protein

The envelope enables the virus to enter and leave a host cell

Many viruses, including those that cause the flu, common cold, measles, mumps, AIDS, and polio,

have RNA as their genetic material

Diseases caused by DNA viruses include

hepatitis, chicken pox, and herpes infections

When the virus contacts a susceptible cell,

protein spikes on its outer surface attach to receptor proteins on the cell’s plasma membrane

The viral envelope fuses with the cell’s membrane, allowing the

protein-coated RNA to enter the cytoplasm. Enzymes then remove the protein coa

An enzyme that entered the cell as part of the virus

uses the virus’s RNA genome as a template for making complementary strands of RNA

Reproductive Cycle of a Typical RNA Virus: The new strands have two functions

1. They serve as mRNA for the synthesis of new viral proteins

2. They serve as templates for synthesizing new viral genome RNA

The new coat proteins assemble around the new viral RNA. Finally, the viruses leave the cell by cloaking themselves in plasma membrane. In other words, the virus obtains its envelope from the cell,

budding off the cell without necessarily rupturing it

Not all animal viruses reproduce in the cytoplasm:

Ex: herpesviruses—which cause chicken pox, shingles, cold sores, and genital herpes—are enveloped DNA viruses that reproduce in a host cell’s nucleus, and they get their envelopes from the cell’s nuclear membrane

The devastating disease

AIDS (acquired immunodeficiency syndrome) is caused by HIV (human immunodeficiency virus), an RNA virus with some nasty twists

HIV has a different mode of

reproduction

HIV has a different mode of reproduction. It is a retrovirus, an RNA virus that reproduces by means of a

DNA molecule, the reverse of the usual DNA > RNA flow of genetic information

These viruses carry molecules of an enzyme called

reverse transcriptase, which catalyzes reverse transcription: the synthesis of DNA from an RNA template

Although there is as yet no cure for AIDS,

its progression can be slowed by two categories of anti-HIV drugs. Both types of medicine interfere with the reproduction of the virus

1. The first type inhibits the action of enzymes called

proteases, which help produce the final versions of HIV proteins

2. The second type, which includes the drug

AZT, inhibits the action of the HIV enzyme reverse transcriptase

Many HIV-infected people take a “drug cocktail” that contains

both reverse transcriptase inhibitors and protease inhibitors

Infectious proteins called prions

cause a number of brain diseases in various animal species, including scrapie in sheep and goats, chronic wasting disease in deer and elk, and mad cow disease (formally called bovine spongiform encephalopathy, or BSE)

In humans, prions cause

Creutzfeldt-Jakob disease, an extremely rare, incurable, and inevitably fatal deterioration of the brain

A prion is thought to be a

misfolded form of a protein normally present in brain cells

When a prion enters a cell containing the normal form of protein, the prion somehow

converts the normal protein molecules to the misfolded prion version. The abnormal proteins clump together, which may lead to loss of brain tissue

To date, there is no known cure for prion diseases,

so hope rests on understanding and preventing the process of infection