Molecular Biology Chapter 18

spontaneous replication errors

1. tautomeric shifts 2. mis-pairing due to other factors 3. incorporated errors and replication errors 4. causes of deletion and insertion

Base analog

Are chemicals with structures similar to those of any of the sour standard nitrogenous base of DNA. If we have 5-Bromouracil it carries the same structure as thyamine except it has bromine atom attached to the 5 Carbon. The 5-Bromouracil is mis-paired with guanine and it creates a transition mutation .

Deamination Chemicals

Can be induced by some chemicals 1. Nitrous acid deaminates cytosine creating uracil which later on during replication pairs with adenine producing a transition from C-G to T-A 2. nitrous acid also can enhance adenine into hypoxanthine which then pairs with cytosine creating a mutation transition from T-A to C-G 3. Nitrous acid can also change guanine into Xanthine and create a mutation transition from C-G to T-A Because both C-G to T-A and T-A to G-C are produced these mutations can be reversed with adding some more of the nitrous acid

radiation

X-ray greatly increase mutation rates in all organisms. Because of the high energies, x-rays, gamma rays and cosmic rays all are capable of penetrating tissues and damaging DNA.

mis-sense mutation

a base substitution that results in a different amino acid in the protein

nonsense mutation

a mutation that changes a sense codon to a nonsense codon. (if a nonsense codon occurs early in the mRNA sequence the protein will be truncated or incomplete and will most likely will be nonfunctional)

forward mutation

a mutation that changes the wild type to phenotype

mutagen

any environmental agent that significantly increases the rate of mutation above the spontaneous rate

somatic mutation

arise in somatic tissues, which do not produce gametes. This type of mutation divides by mitosis and will be passed to the daughter cells, which then leads to genetically identical cells These mutations can stimulate cell division and cause cancer

Germ-like mutations

arises in cells that produce gametes. This type of mutation can be passed to future generations which then produce offsprings that carry the mutation in all their somatic and germ like cells. Most of the multicellular mutation carry this type of mutation These mutation can be divided into gene mutations and affect a single gene. They can also divid into chromosome mutation and affect the number or structure of a chromosome

lethal mutation

causes premature death

gain of function mutation

causes the cell to produce protein or a gene product whose function is not normally present this mutation is frequently dominant Example: if we have a mutation in a gene that encodes a growth factor or and that might cause the mutated receptor to stimulate growth all the time even in the absence of the growth factor

loss of function mutation

causes the complete or partial absence of normal protein function. This mutation is frequently recessive Examples: alternating a nonfunctional protein in the sequence alternating a protein that affects the process of translation, transcription and splicing of the protein

reverse mutation

changes a mutant phenotype back to the wild-type phenotype

inframe insertion and deletion

indels that don't affect the reading frame

FMR 1 mutation

is a disease that causes a fragile X syndrome at the end of X tip chromosome people with this disease may harbor around 100s or even 1000s of copies of CGG in their alleles.

suppressor mutation

is a genetic change that hides the effect of another mutation. This mutation carries two types of mutations intergenic and intragenic

neutral mutation

is a mis-sense mutation that alters the amino acid sequence of a protein but does not significantly change its function. This mutation occurs when once amino acid is replaced by another that is chemically similar or when the affected amino acid has little influence on protein function

Insertion and deletion (indels)

is a type of basic mutation. In this mutation nucleotide pairs are either added or removed. This type of mutation leads to frameshift mutation

frameshift mutation

is changing in the reading frame of the gene. This type of mutation usually alters all of the amino acids encoded by the nucleotides following the mutations, so this means that they have drastic effects on the phenotype. Some of these mutations introduce pre mature stop codon term

Replication Error

is detected by an incorporated error, it is a permanent error that creates a permanent mutation. For the mutation, all base pairings will seem correct and there is no way for the repair system to detect the error

base substitution

is the alternation of a single nucleotide in the DNA. There are two types this mutation: 1. transition and transversion. 2. insertion and deletion

depurination

is the loss of a purine base from a nucleotide, the result of this process is that a covalent bond connecting the purine to the 1'-Carbon atom of the deoxyribose sugar breaks producing an apurinic site, which is a nucleotide that lacks a purine base. An apurinic site cannot act as a template for a complementary base in replication. In the absence of base pairing constraints, an incorrect nucleotide is incorporated into the newly synthesized DNA strand opposite the apurinic site, leading to an incorporated error.

deamination

is the loss of an amino acid from a base and that causes alternation of pairing properties of a base

silent mutation

is when a codon is changed to synonymous codon that specifies the same amino acid. Alternating the DNA sequences without changing the amino acid sequence of the protein

incorporated error

is when a mis-paired base has been induced into a newly synthesized nucleotide chain.

expanding nucleotides

is when a mutation in which the number of copies of a set of nucleotides increase

transition

is when a purine is replaced by a different purine or a pyramidine is replaced by different pyramidine

transversion

is when a purine is replaced by a pyrimidine

mutation rate

is when a wild type allele changes into a mutant allele, this change could be in the number of mutations per biological unit, which means that it could be mutated per cell division, per gametes or per round of replication. This mutations provides information about how often a mutation arises.

tautomeric shifts

is when the positions of protons (hydrogen atoms) in the DNA base changes. They are different than the normal watson and crick base pairing instead the DNA base pairing exist in a different chemical form. So instead of having thyamine pairing adenine or guanine pairing with cytosine would have different tautomer bases paring differently for example tautomer cytosine is going to pair with adenine

Ionizing radiation

it dislodges electrons from the atoms they encounter, changing stable molecules into free radicals and reactive ions and that would change the structure of bases and break phosdiaster bond in DNA. Trying to repair these breaks can produce chromosome mutations

anticipation phenomenon

it is caused by the expansion nucleotides and it becomes more severe in each generation. The number of copies of repeats correlates with its instability when more repeats are present, the probability of expansion to even more repeats increase. This association between the number of copies of nucleotides repeats, the severity of the resulting disease, and the probability of expansion

mutation

it is the inherited change in genetic information and the descendants that inherit the change may be the cells or organisms

strand slippage

occurs when one nucleotide strand forms a small loop. If the looped out nucleotides are on the newly synthesized strand an insertion results then this insertion will be replicated and both strands will contain it. If the looped out nucleotides are on the template strand then we will have a deletion and it will be continuous in the next rounds of replication.

intergenic mutation

takes place in a gene other than the one carrying the original mutation that it suppresses

intragenic mutation

takes place in the same gene that contains the mutation being suppressed

tri-nucleotide repeats

the expansion of three set of three nucleotide is what causes most of the human diseases

spontaneous mutations

these are the types of mutations that occur under normal conditions

induced mutations

they are caused by environmental changes, chemical, and radiation changes

Alkylating Agents

they are chemicals that donate an alkyl group such as methyl and ethyl group Examples: 1. ethylmethylsulfonate (EMS) adds an ethyl group to guanine and it creates a transition C-G to T-A. 2. It is also capable of adding an ethyl group to thyamine creating 4-ethylthyamine which then pairs with gunaine and it creates a transition T-A to G-C. Sine EMS creates both transitions it can be reversed by an addition of EMS .

conditional mutation

they are expressed under certain conditions and they can affect the phenotype under an elevated temp.

ultraviolet radiation

they have less energy than Ionizing radiation, they don't dislodge electrons. They are highly mutagenic. Pyramidins end up absorbing these lights and create pyramidine dimers

mis-pairing due to other structures

this takes place because of wobble, in which normal protonated and other forms of all bases are able to pair due to flexibility in the DNA helical structure. These structures are detected in DNA molecules and they are thought to be the reason why there are so many of those defects in replication.

mutations take place during DNA replication

where does mutation take place?