subject guide notes

D1.3.1—Gene mutations as structural changes to genes at the molecular level

most common mutations are: insertions, deletions, and substitutions

  • cause structural changes to gene

D1.3.2—Consequences of base substitutions

SNPs are the result of base substitution mutations & are most common type of genetic variation

  • due to degeneracy of genetic code, the change in the DNA sequence may or may not hv an effect on structure of protein

    • depends if substitution is synonymous or non-synonymous

D1.3.3—Consequences of insertions and deletions

frameshift mutations are caused by either insertions or deletions

  • alter the reading frame of the codons DNA

    • changing even one nucleotide in the DNA sequence, means that the wrong mRNA sequence is transcribed (the mRNA sequence is missing a codon, or has the wrong codon)

    • this means there is wrong order of amino acids during translation, and therefore the wrong protein is synthesised, or the protein has the wrong shape & loses its functionality

D1.3.4—Causes of gene mutation

can occur by errors in DNA replication or repair, or can be caused by mutagens

2 types of mutagens - chemical & radiation

examples of chemical mutagens: mustard gas, nitrous acid, formaldehyde, and more

  • specifically for nitrous acid, it can convert cytosine to uracil through deamination, making it mutagenic

  • this can result in errors during DNA replication & repair, potentially causing mutations

exposure to radiation can damage DNA, resulting in single-strand breaks, double-strand breaks, or chemical modifications to DNA bases

  • can disrupt DNA replication

  • can cause cancer

    • ex: single-stranded break in occurring in DNA template strand can impact movement of replication fork

    • can disrupt continuity of replication fork, resulting in replication errors, or breaks in replication all together

D1.3.5—Randomness in mutation

mutations can occur anywhere in base sequence of genome

certain bases do hv higher susceptibility to mutations than others

  • ex: cytosine has higher mutation rate than other nitrogenous bases, as it can undergo a reaction called deamination, where it loses an amino group

    • results in conversion of cytosine to uracil

environmental conditions could also impact frequency & types of mutations

D1.3.6—Consequences of mutation in germ cells and somatic cells

mutations in somatic cells can cause diseases in a person’s lifetime

  • mutations in somatic cells aren’t heritable

  • so the mutations may cause cancer during the person’s lifetime, but the mutations wont be passed on to offspring

mutations in germ cells are heritable

  • can alter chromosome number or gene sequence in gametes

  • can increase the offspring’s susceptibility to certain diseases, or can cause genetic disorders

D1.3.7—Mutation as a source of genetic variation

gene mutation is the original source of genetic variation

can be harmful or beneficial for organism, but in the long term, they’re essential for evolution by natural selection

D1.3.8—Gene knockout as a technique for investigating the function of a gene by changing it to make it inoperative

gene knockout helps scientists understand the role of certain genes, in the organism’s growth or development

  • understanding the gene’s role can help improve treatments

library of knockout organisms are available for scientists

  • are organisms that hv been genetically modified to hv one or more of their genes, knocked out

D1.3.9—Use of the CRISPR sequences and the enzyme Cas9 in gene editing

is composed of enzyme Cas9

scientists created single-guide RNAs to target specific genes for modification or deletion

  • it will target & bind to a specific DNA sequence

  • will guide Cas9 enzyme to that location

  • allows it to make cuts to the DNA, resulting in double-strand breaks

  • scientists can then add, modify, or delete the DNA at the location of the cuts

CRISPR technology has been used in:

  • gene therapy - has potential to correct mutations that cause diseases (such as sickle-cell anemia)

  • agriculture, in order to increase crop yield & disease resistance

  • disease modelling in animals

  • genetic engineering of microorganisms & can enhance their ability to produce important compounds

D1.3.10—Hypotheses to account for conserved or highly conserved sequences in genes

one hypothesis is functional constraints

  • are selective pressures that prevent accumulation of mutations, as these can impact an organisms survival

second hypothesis is slower rates of mutations

  • natural selection pushes mutation rates down by power of random genetic drift

HBA chain (codes for haemoglobin alpha chain) is example of highly conserved sequence