Genetic Mutations: Types, Causes, and Consequences in Bioinorganic Chemistry, Study notes of Inorganic Chemistry

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Bioinorganic Chemistry

CHEM-

Genetic Mutations

Genetic Mutations

Mutations are considered the driving force

of evolution, where less favorable

(or deleterious) mutations are removed from

the gene pool by natural selection, while

more favorable or beneficial mutations tend

to accumulate, leading to continuous continuous

evolution evolution.

Neutral mutations are those that do not affect

the organism's chances of survival in its

natural environment. These mutations can

accumulate over time, and can result in what

is known as punctuated equilibrium punctuated equilibrium which

result in non-continuous evolution. non-continuous evolution.

Mutations

Mutations

In multicellular organisms, mutations can

be subdivided into germline

mutations, which can be passed on to

progeny and somatic mutations, which

(when accidental) often lead to the

malfunction or death of a cell and can lead

to cancer.

DNA has so-called recombination hotspots,

where mutations occur 100 to 1000 times

more frequently than the normal mutation

rate. A hotspot is usually a region of 1.5 to

2.0 kb. Abou 25,00o hot spots have been

Mutations

Mutations



Organisms have many ways of proofreading and

repairing damaged or mutated DNA. Most

mistakes are repaired, however some of them are

not and may lead to genetic diseases.

 Mutation rates also vary across species.

Evolutionary Biologists have theorized that higher

mutation rates may be beneficial in some

situations, because they allow organisms to evolve

and therefore adapting faster to their changing

environment.

Mutations

Mutations

Causes of mutation

Spontaneous mutations

Spontaneous mutations

Deamination ap-site

Loss of A or G; they occur 1000 times each

day in mammals

Deamination to base analogs is estimated

to occur 100 times each day in mammals,



Cytosine (C) Uracil (U), or



Adenine (A)  Hypoxanthine(HX)

Cytosine Uracil

Mutations

Mutations



Transition Transition, a base pair substitution in which the

orientation of the purine and pyrimidine bases on

each DNA strand remain the same; i.e., AT to GC, TA

to GC ...



Transversion Transversion, a base pair substitution in which the

purine-pyrimidine orientation on each DNA strand is

reversed; i.e., AT to TA



Frameshift mutation Frameshift mutation , always involves insertion or

deletion, never a substitution, of one or more

nucleotides, usually through a polymerase error

when copying repeated sequences, it leads to a shift

in the subsequent reading of the nucleotide triads.



Oxidative damage Oxidative damage caused by oxygen radicals

Mutations

Mutations

Although a point mutation is usually the

change of a single nucleotide in DNA. It can

also be the deletion of a single nucleotide, or

just a few base pairs that affect the function

of a single gene.

A point mutation can be reversed by

another point mutation, in which the

nucleotide is changed back to its original

state (true reversion).

a second-site reversion (a complementary

mutation elsewhere that results in

regained gene functionality).

Point Mutations

Point Mutations

Mutations

Mutations

Point Point

Mutations

Mutations

Mutations

Mutations

Deletion: remove one or

more nucleotides from the

DNA, shortens the DNA.

These mutations are

irreversible and they can

alter the reading frame of the

gene.

Large Scale

Large Scale

Mutations Mutations

Duplication: repeats a set of nucleotides from the

original DNA, resulting on a longer DNA. Like

insertions, these mutations can alter the reading

frame of the gene.

Inversion: reverses a segment of nucleotides from

the DNA, it doesn’t alter the length of the DNA.

These mutations alter the reading frame of the

When the number of nucleotides is a multiple of

three, they may result is less serious consequences.

Huntington’s disease involves repeated trinucleotide

CAG which inserts extra glutamins (Gln) to the

encoded protein. This causes increased level of a

brain protein that causes apoptosis.

Large Scale Mutations Large Scale Mutations

Insertion: ranges from one to

thousands extra nucleotides into

the DNA. These mutations are

also called indels indels, for

insertion/deletion.

They are usually errors during

replication of repeating elements

(e.g. AT repeats).

arge Scale Mutations

arge Scale Mutations

Reciprocal translocation

generates the Ph1 gene

associated with leukemia

chromosome Ph

1

Induced mutations Induced mutations

These mutations at the molecular level can be caused by

specific but sometimes simple chemical substances

Chemically induced mutations by

 Nitrosoguanidine (NTG)



Base analogs (e.g. BrdU)

 Simple chemicals (e.g. acids)



Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU))

 Methylating agents (e.g. ethane methyl sulfonate (EMS))



DNA intercalating agents (e.g. ethidium bromide)

 DNA crosslinker (e.g. platinum)



Oxygen radicals

Mutations

Mutations