D1.3 Mutation and gene editing

Gene mutations definition

random, permanent and heritable structural changes to the DNA (base sequence) of a gene

3 main types of gene mutation

• insertions

• deletions

• substitutions

insertions

one or more extra nucleotides are inserted into the DNA (base sequence) of the gene

deletions

one or more nucleotides are removed from the DNA (base sequence) of the gene

Substitutions

one base is replaced by another base, changing one codon into a different one

3 base substitution mutation categories

• neutral - no effects

• deleterious (causing harm) - lethal

• beneficial - rare

what kind of base substitutions affect amino acid sequences of polypeptides

• changes to the coding sequences of genes affect the amino acid sequence

• base substitutions in the non-coding DNA between genes on chromosomes are unlikely to have any effect → neutral

same-sense (synonymous) mutations

• base substitutions that change one codon for an amino acid to another codon for the same amino acid

• can occur due to the redundancy of genetic code

• do not affect phenotype

• may cause a second mutation to change the codon into one for a different amino acid

nonsense mutations

• change a codon for an amino acid into a stop codon → translation is terminated

• results in a protein that is unlikely to function properly due to being incomplete

• consequence depends on what the protein’s function is

mis-sense mutations

• change a codon for one amino acid into a codon for another amino acid

• → one amino acid in the polypeptide is different

• may not have much effect if the new amino acid has a similar structure + chemical properties as the original (synonymous substitution) or if it is positioned in a part of the protein that is not critical to its function

• can also have severe + lethal effects e.g. sickle cell

single nucleotide polymorphisms (SNP’s)

if a base substitution spreads by inheritance until 1% or more of the population has it

what happens when a multiple of 3 nucleotides is inserted or deleted

• extra/missing whole codon in the mRNA transcribed from the gene

• the amino acid sequence of the polypeptide translated from the mRNA will be unchanged apart from one or more extra/missing amino acids

what happens when not a multiple of 3 nucleotides is inserted or deleted

• frameshift mutations

• every codon is changed from the insertion/deletion onwards in the direction of transcription and translation

• can introduce stop codons → earlier ending of translation → production of a truncated polypeptide → prevents proper functioning

insertions + deletions on the structure of a polypeptide

• even if a single amino acid is inserted or deleted the structure of a polypeptide is likely to be radically changed → prevents it from functioning properly

• happens with all frameshift mutations + major insertions + deletions

when is mutation most likely

• mutation can happen at any time

• most likely during DNA replication when errors in base pairing are sometimes made

• → low background frequency of mutation due to infrequent but unavoidable changes

what are mutagens

• agents that increase the frequency of mutation above the natural background level

• many mutations are harmful and some leathal → all mutagens are dangerous

categories of mutagens

• chemical mutagens

• high energy radiation

chemical mutagens definition

substances that cause chemical changes in DNA that result in changes to the base sequence

chemical mutagens examples

• nitrosamines in cigarettes and other forms of tobacco

• mustard gas used in the past as a chemical weapon

• benzene a solvent that is widely used in industry

high energy radiation definition

• breaks bonds in strands of DNA allowing nucleotides and therefore bases to be inserted or deleted

• can also cause chemical changes in bases resulting in base substitutions

• many forms of short-wave electromagnetic radiation are mutagenic

examples of high energy radiation

• X-rays emitted by radioactive elements such as radon

• beta particles from radioactive isotopes such as iodine-131 and caesium-137, which were released in Chernobyl

• medium-wave (UVB) and short-wave (UVC) ultraviolet radiation = components of sunlight but mostly absorbed by stratospheric ozone

• (gamma rays from radioactive isotopes such as cobalt-60 consists of sub-atomic particles)

what can and can’t organisms control about mutation

• can: to a limited extent control their overall mutation rate

• can’t: what mutations occur and when

what might affect what mutations occur

• mutations are mostly random though some have a higher probability of occurring than others

• e.g. are affected by:

• what the adjacent bases are

• chemical similarity

• there is also variation in the frequency of mutation according to the position of DNA within the genome + its function

somatic cells definition

body cells that cannot develop into gametes → genes are not inherited by offspring

consequences of somatic cell mutations

• limited

• even a lethal mutation will only kill one somatic cell which can be replaced

• mutation of somatic genes that control the cell cycle → more serious consequences (can cause cancer) as it can result in uncontrolled cell division and tumor formation → if the tumors spread invasively they are malignant

cancer definition

the growth of malignant tumours

germ cells definition

• gametes or cells that can develop into gametes

• in humans germ cells are located in the testes and ovaries

gene mutation in gametes

• if a gene mutates in a germ cell → gametes produced can carry the mutation → mutation can be passed down to offspring.

• initially only the zygote has the mutation (however every cell in a multicellular organism is derived from the zygote by mitosis → all carry the mutation

• this makes it difficult to carry out gene therapy

germ line definition

the continuous chain of cells through which genes are passed from generation to generation

mutation + evolution

• long term survival of a species would be threatened if no mutation ever occured

• natural selection + evolution can only occur if there is genetic variation

• Mutation is the original source of all genetic variation

• for the organism → mutation is usually harmful

• for the species → in the long term mutation is vital

• when environmental change occurs → few mutations will be beneficial because they make individuals better adapted to the new conditions

how does mutation increase genetic variation

new alleles produced by gene mutations enlarge the gene pool of a population and provides more variation on which natural selection can operate