Effects of Mutations (College Board AP Biology)

• Mutations occur spontaneously and randomly during DNA replication
• As the DNA base sequence determines the sequence of amino acids that make up a protein, mutations in a gene can sometimes lead to a change in the amino acid sequence coded for by the gene
• Most mutations do not alter the polypeptide or only alter it only slightly so that its structure or function is not changed
• Because in the genetic code, more than one triplet code codes for the same amino acid, some mutations will not cause a change in the amino acid sequence
  • Substitution mutations are the mutations that usually have a smaller effect on the polypeptide and the resultant phenotype

• Some gene mutations change all base triplets downstream from (after) the mutation, this will result in a nonfunctional polypeptide
  • Insertion and deletion mutations result in a frameshift

 The effect of gene mutations on polypeptides 

• Most mutations do not alter the polypeptide or only alter it slightly so that its appearance or function is not changed
• However, a small number of mutations code for a significantly altered polypeptide with a different shape
• This may affect the ability of the protein to perform its function. For example:
  • If the shape of the active site on an enzyme changes, the substrate may no longer be able to bind to the active site
  • A structural protein (like collagen) may lose its strength if its shape changes

The effect of gene mutations on phenotype

• Polypeptides / proteins affect the phenotype of an organism via specific cellular mechanisms
• If a mutation causes a major alteration in a polypeptide then cellular mechanisms could be affected, which may impact the phenotype of the organism
• For example, a mutation in the TYR gene in humans affects the structure of an enzyme that is needed for the production of the pigment melanin
  • The phenotype of the human is affected by the lack of melanin
  • Individuals with the mutation have albinism; very pale skin and unpigmented (white) hair

Cystic fibrosis

• Cystic fibrosis is a genetic disorder of cell membranes resulting from a mutation event
  
  • It results in the body producing large amounts of thick, sticky mucus in the air passages
  • Over time, this may damage the lungs and stop them from working properly
• Cystic fibrosis is caused by a recessive allele (f)
• A common variant of the mutation is a four-base deletion that causes deletion of one amino acid (phenylalanine) in position 508 in the polypeptide chain of the CFTR protein
  • This renders the protein unable to attach to the relevant plasma membrane
• In another variant, transcription is stopped artificially early, so no protein is produced

This means:

• People who are heterozygous (only carry one copy of the recessive allele) won’t be affected by the disorder but are ‘carriers’
• People must be homozygous recessive (carry two copies of the recessive allele) in order to have the disorder
• If both parents are carriers, the chance of them producing a child with cystic fibrosis is 1 in 4, or 25%
• If only one of the parents is a carrier (with the other parent being homozygous dominant), there is no chance of producing a child with cystic fibrosis

Whole chromosome mutations

• Errors in mitosis or meiosis can result in changes in phenotype
• Changes in chromosome number often result in new phenotypes, including sterility caused by triploidy, and increased vigor of other polyploids
• Changes in chromosome number often result in human disorders with developmental limitations, including Down syndrome/Trisomy 21 and Turner syndrome
  • In Down Syndrome, (also called Trisomy 21), nondisjunction occurs during anaphase I (in this case) and the 21st pair of homologous chromosomes fails to separate
  • Individuals with this syndrome have a total of 47 chromosomes in their cells as they have three copies of chromosome 21
  • The impact of trisomy 21 can vary between individuals, but some common features of the syndrome are physical growth delays and reduced intellectual ability
    • Individuals can also suffer from issues with sight or hearing
• Other trisomy syndromes
  
  • There are other trisomy possibilities that can result from nondisjunction; many, but not all, have very serious impacts on the phenotype of the offspring which may be fatal
  • Patau syndrome (trisomy 13) and Edwards syndrome (trisomy 18) are very serious syndromes which result in many physical disabilities and developmental difficulties
  • Trisomy 18 and 13 both have very low survival rates with few babies surviving past their first birthday
  • Klinefelter's syndrome is caused by nondisjunction in sex chromosomes which leads to having the chromosomes XXY
    
    • This syndrome is often not diagnosed until adulthood and doesn't impact life expectancy but may have a negative effect on fertility
  • Turners syndrome also affects the sex chromosomes with individuals possessing just one X chromosome
    
    • Individuals with Turner's syndrome would not necessarily have a reduced life expectancy, although will often be shorter and may suffer some symptoms such as lack of sexual development during puberty