Download Errors in the Code

Errors in the Code
Slide 2
Mutations are not just the stuff of science fiction movies. Mutations
happen every day in all kinds of cells in all kinds of organisms. A mutation is a change
in an organism’s DNA that can be passed on to other cells or offspring. There are many
different kinds of mutations that are categorized by where they occur. We will look at
somatic and germ-line mutations, point and chromosomal mutations, and spontaneous
and induced mutations.
Slide 3
In a single-celled organism any change in the DNA will be passed on to its
“offspring” when the cell divides and gives rise to two new cells because each daughter
cell receives an exact copy of the DNA. For multicellular organisms two different types
of mutations may arise. Somatic mutations occur when the DNA in a non-gamete cell is
altered. These mutations are passed on to daughter cells when the original cell divides
during mitosis. Somatic mutations may adversely affect the organism, but cannot be
passed on to the organism’s offspring. Skin cancer is an example of a somatic mutation.
Germ-line mutations are found in gametes or cells that give rise to gametes. These
mutations can be passed on to offspring, but do not adversely affect the parent. Down
Syndrome, when a gamete receives three copies of chromosome 21, is an example of a
germ-line mutation.
Slide 4
Point mutations involve an alteration of a single base in a DNA molecule.
The first of the 4 types of point mutations is called a silent (or synonymous) mutation.
Recall that the genetic code is redundant, that is, there may be more than one codon that
codes for a specific amino acid. For example there are four codons for leucine, two
codons for glutamic acid, three stop codons, and so on. A silent mutation is one in which
a base is changed, but the resulting mRNA still codes for the same amino acid. These
mutations have no adverse effects on the organism because the correct protein is still
synthesized. Silent mutations are very useful in phylogenetics as we will see later in the
course.
Slide 5
Missense mutations occur when a base in the DNA is changed, resulting in
a codon for a different amino acid. The resulting polypeptide has one incorrect amino
acid in its sequence. These mutations usually have consequences for the organism
because the resulting protein may not have the correct shape and therefore may not
function correctly. In many cases missense mutations cause a protein to function less
efficiently than the correctly formed protein, so an organism may be able to survive with
this type of mutation. Sickle cell disease is an example of a missense mutation
.
Slide 6
Nonsense mutations have more serious consequences for an organism. In
nonsense mutations, a base is changed such that a stop codon is inserted into the mRNA
sequence. Translation terminates prematurely, leaving a truncated polypeptide sequence
that may not form a functional protein. The organism may be left without a protein that
is essential to life.
Slide 7
Frame-shift mutations involve the insertion or deletion of a base in the
DNA sequence. Remember that codons are like a series of 3-letter words. Inserting an
extra letter in or deleting a letter from the sequence will move all of the other letters over
one, but the translation machinery is still going to read the sequence three letters at a
time. All of the codons after the insertion will code for different amino acids, and the
resulting polypeptide sequence will essentially be random. This type of mutation also has
serious consequences for the organism because essential proteins may not by synthesized.
Slide 8
There are also 4 types of chromosomal mutations – mutations that involve
pieces of a chromosome rather than just a single base. A deletion is exactly what it
sounds like – part of the chromosome breaks into two pieces; a segment of the
chromosome is lost, and the remaining pieces join together. This type of mutation can
have consequences similar to those arising from a frame-shift mutation. The 3-letter
codons will be out of register and will code for the wrong amino acid sequence.
Slide 9
When a chunk of a chromosome gets deleted, as in the last slide, what
happens to it? When homologous chromosomes break at different points and reconnect
with the wrong partners as in this example, one chromosome ends up with a deletion
while the other has a duplication.
Slide 10
Sometimes a deleted piece of a chromosome will be flipped over before it
is reinserted into the chromosome. Now part of the genetic code is running in the
opposite direction. Any resulting protein would be seriously altered and probably nonfunctional. This type of mutation is called an inversion.
Slide 11
That broken piece of chromosome may meet another fate. When a
segment of chromosome breaks off one chromosome and is reinserted into a different
chromosome, translocation has occurred. The example here shows a reciprocal
translocation. Non-homologous chromosomes have exchanged segments. This type of
mutation can cause problems during meiosis.
Slide 12
How do all these types of mutations arise? Spontaneous mutations occur
because DNA replication, while extremely accurate, is not perfect. Instability in the
chemical structures of the nucleotide bases can lead to errors in base pairing during DNA
replication. Although proofreading catches most of these errors, some slip by.
Chromosome breakage leading to translocations and inversions can occur during meiosis
also, giving rise to germ-line mutations.
Mutations may be induced, that is, they may be caused by some environmental factor that
alters the DNA. It is pretty common to hear that certain chemicals are carcinogenic.
Usually the reason they are carcinogenic is that they are also mutagenic or mutationcausing. These types of chemicals may alter the base pairing properties of the nucleotide
bases or interfere with a base’s ability to pair at all. Different types of radiation, such as
X-rays and ultraviolet radiation, are well-known mutagens and are sometimes used in
genetic experiments to induce mutations.
Slide 13
Mutations are occurring inside our bodies every day. The frequency of
mutations in DNA replication is about 1 mutation in 104 base pairs, but proofreading and
repair reduce that frequency to about 1 mutation in 109 base pairs. Still, with all the cells
in our bodies and the rate at which they divide, at least during some parts of our lives,
that seems like a lot of mutations. Why aren’t we all X-men? Remember that we have
an enormous amount of DNA in each of our cells, but not all of it contains genes that are
expressed. Some parts of our DNA simply don’t contain genes while other parts may
contain genes that aren’t switched on. Mutations, being random, often occur in the parts
of our DNA that don’t contain genes. Also, due to the redundancy in the genetic code,
many mutations are silent and don’t affect protein synthesis.
Mutations are important in evolution because they provide genetic variability on which
natural selection can act. Remember that mutations are random – some are
advantageous, many are neutral, but many are harmful to an organism. Harmful
mutations are usually lethal and less likely to be passed on to the next generation. If the
mutation provides an advantage for the organism it can be passed on to subsequent
generations, eventually becoming part of the gene pool for the species. Natural selection,
however, is not random and selects the individuals best suited to their environment.