Exam 3 DNA mutation

mutation

an alteration in DNA sequence → major alteration in chromosomal structure

any base-pair change in sequence

single base pair substitution or deletion/insertion of base pairs

can occur in somatic or germ cells or in coding or noncoding regions

point mutation

base substitution

change from one base pair to another

missense mutation

results in new triplet code for different amino acid

nonsense mutation

results in triplet code for stop codon (translation terminated prematurely)

silent mutation

new triplet code still codes for same amino acid

transition base substiution

pyrimidine replaces pyrimidine or purine replaces purine

transversion base substitution

purine and pyrimidine are interchanged

frameshift mutation

result from insertions or deletions of base pair

loss or addition of nucleotides causes a shift in reading frame

frame of triplet reading during translation altered

loss of function mutation

reduces/eliminates function of gene product

null mutation

results in complete loss of function

dominant mutation

results in mutant phenotype in diploid organism

dominant gain-of-function mutation

results in gene with enhanced, negative, or new function

lethal mutations

interrupt essential process and result in death

various inherited biochemical disorders (tay sachs)

lethal conditional mutations

dependent on organisms’ environment

temperature-sensitive mutation

gene product functions at one temperature but not another

ex: temperature sensitive coat color variations in Siamese cats and himalayan rabbits

neutral mutation

occurs in protein-coding region in any part of genome

majority of mutations occur in noncoding region

effect on genetic fitness of organism is neither beneficial nor detrimental

visible (morphological) mutation

seen in phenotype

ex: mendel’s pea characteristics

nutritional mutation

altered nutritional characteristics

ex: loss of ability to synthesize an essential amino acid in bacteria

biochemical mutation

changes in protein function

ex: defective hemoglobin leading to sickle-cell anemia in humans

behavioral mutation

behavior pattern changes

ex: brain mutations affecting drosophila mating behaviors

regulatory mutation

altered gene mutation

ex: mutation affecting expression of the lac operon in E.coli

somatic mutation

occur in any cell except germ cells; are not heritable

germ-line mutation

occur in gametes; are inherited

autosomal mutation

occur within genes located on autosomes

X and Y linked mutations

occur within genes located on X and Y chromosome

recessive autosomal mutation

occurs in somatic cell of diploid organism

is unlikely to result in detectable phenotype

inherited autosomal mutation

are expressed phenotypically in first generation

x-linked recessive mutation

arise in gametes of homogametic female

may be expressed in hemizygous male offspring

E coli + T1 bacteriophage

e coli is susceptible to infection by T1 bacteriophage

some rare strains of E.coli are resistant; resistant strains arise in cultures infected with T1

Luria and Delbruck fluctuation experiment

if mutations are adaptive, T1 resistance will not occur until T1 is added to culture

proportion of resistant cells will be the same for all identical cultures

if mutations occur spontaneously the number of T1 resistant cells will vary

mutation rates in humans

2.5 × 10^-8 per site per generation

about 175 mutations per generation

substitutions are 10x more common than insertions or deletions

occur more frequently in males than females

spontaneous mutations

changes in nucleotide sequence that occur naturally

arise from normal biological or chemical processes that alter nitrogenous bases

they are usually mistakes that occur during replication

rates vary but are exceedingly low for all organisms

induced mutations

result from influence of extraneous factors, either natural or artificial

radiation, UV light, natural and synthetic chemicals

factors that cause mutation during replication

replication is imperfect

DNA polymerase occasionally inserts incorrect nucleotides

misincorporated nucleotides persist after proofreading

errors due to mispairing predominantly lead to point mutations

replication slippage

when a loop occurs in template strand during replication, DNA polymerase misses looped out nucleotides and small insertions and deletions occur

most common in repeat sequences (hot spots): contribute to hereditary diseases: Fragile-X, huntington disease

tautomers

alternate chemical forms of purines and pyrimidines

increase chance of mispairing during DNA replication

tautomeric shifts

change the bonding structure allowing for non complementary base pairing

may lead to permanent base-pair changes and mutations

ex: keto from to enol form: removal of a hydrogen atom rearranges chemical bonds, many compounds shift back and forth from one form to another

depurination

loss of nitrogenous bases (usually a purine- guanine or adenine), leading to an apurinic site (without purine)

deamination

amino group in cytosine or adenine is converted to uracil and adenine converted to hypoxanthine leading to a proton shift

results in change in base pairing of original bases (A-T converted to G-C)

oxidative damage to DNA

due to by-products of normal cellular processes

exposure to high-energy radiation

superoxides (O2-)

hydroxyl radicals (OH)

hydrogen peroxide (H2O2)

free radicals

stable molecules transformed into chemical species containing one or more unpaired electrons

directly or indirectly affect DNA: alter purines and pyrimidines, break phosphodiester bonds, produce deletions, translocations, or fragmentation

diet w/ free radicals

the more you eat, the more ATP is generated

the more ATP you generate the more O2 is broken down into individual, unstable oxygen atoms

oxygen atoms always grab electrons leading to chemical changes in DNA molecules

transposable elements

DNA elements that move within or between genomes

present in all organisms

can act as naturally occurring mutagens

cause inversions, translocations, double-stranded breaks- creates chromosomal damage

mutagens

natural artificial agents that induce mutations

all cells are exposed to them

ex: fungal toxins, cosmic rays, UV light, industrial pollutants, medical x-rays, chemicals in tobacco smoke

base analogs

mutagenic chemicals that mimic DNA bases

can substitute for purines or pyrimidines during nucleic acid biosynthesis

increase tautomeric shifts

increase sensitivity to UV light- mutagenic

ex: 5-bromouracil behaves as thymine analog

alkylating agents

donate alkyl group (CH3 or CH3CH3) to amino or keto groups in nucleotides

alter base-pairing affinity

transition mutations result

ex: mustard gas

intercalating agents

chemicals with dimensions and shapes that wedge between DNA base pairs

this causes base-pair distortions and DNA unwinding → replication errors

ex: ethidium bromide

adduct-forming agents

mutation causing chemicals

covalently binds to DNA, altering conformation and interfering with replication and repair

ex: acetaldehyde or heterocyclic amines (cancer causing chemicals)

UV light

creates pyrimidine dimers; two identical pyrimidines distort DNA conformation

errors can be introduced during DNA replication

ionizing radiation

energy of radiation varies intensely with wavelength: mutagenic are x-rays, gamma rays, cosmic rays

penetrates deeply into tissues, causes ionization of molecules