The pre-mRNA breaks and separates from the DNA template strand, which then returns to its original form by rewinding into a double helix again. It then moves out of the nucleus into the cytoplasm through nuclear pores.
Within the pre-mRNA there are regions which do not code for any amino acid (non-coding regions) and are not expressed, there are also regions called exons which do code for amino acids and are expressed. The non-coding regions are called introns and need to be removed in order for the amino acid sequence to be correct.
Εndonuclease enzymes contribute to the removal of the introns (Limited, 2016), leaving just the exons. However they may also be some introns left acting as a stop codon. The exons then join together to form the mRNA strand.
Now that the mature mRNA is assembled it is ready to be translated, a process which takes place in the cytoplasm. Firstly, mRNA is transferred into the ribosome and attaches to it by binding two codons to the small sub unit (Annets, et al., 2016), responsible for protein synthesis. The mRNA is placed between the ribosomes smaller and larger separate subunits as shown in Figure 11.
Now that it’s in position tRNA molecules bind to the codons one by one. Transfer RNA (tRNA) is a type of nucleic acid that has an amino acid attached to it along with an anticodon specific to the mRNA’s codons. The first tRNA that bonds always has an UAC anticodon complimentary to the first AUG codon on the mRNA. After that the second tRNA molecule carrying an amino acid bonds to the second codon. The tRNA molecules that detach on order to bring another amino acid to the ribosome. This process continues until a stop codon is reached (non-coding). In the meantime, amino acids which are next to each other form peptide bonds resulting in a polypeptide chain as shown in Figure 12. The chain then detaches at the end of the process which is then further modified to carry out its function.
Sometimes the process of protein synthesis does not complete as intended to. Mutations can occur that alter bases and as a result the proteins are also altered. There are different types of mutations that will be analysed in detail further on however it is important to first understand what they are and what causes them.
Mutations are alterations in the sequences of DNA bases possibly resulting in change of an organism’s behaviour, physiology and aesthetics (Understanding Evolution, n.d.). Although they are the reason behind evolution they can also be detrimental to the human species.
Causes of Mutations
Genetic mutations can be hereditary or acquired from external factors. If the DNA is inherited from one or both of the parents, every gene in every cell in of the child’s body will have the same germline mutation. Unfortunately, there is very little control one has over inherited mutations.
On the other hand, somatic mutations are caused by external/environmental factors such as failure to successfully copy DNA base sequences during replication, ultraviolet (UV) radiation from the sun. These types of mutations do not take place in all cells but only some. In a few cases both parent’s egg and sperm cells may not have a mutation, however the offspring might have acquired a somatic mutation from another factor (mosaicism) that was later inherited by other cells during early embryonic development (Genetics Home Reference, 2019).
Other causes include imbalanced chemical composition of purine and pyrimidine bases during replication and chemical carcinogens. Note that point mutations may also be caused by hydrolytic damage to the cytosine base, by deamination. This is the removal of an amine group from a molecule (Figure 13), (Biotech Khan, 2014). The result of this is a mutant daughter cell where the C-G base pair is replaced by T-A (Lodish Harvey, et al., 2000).
There are various types of mutations all leading to specific diseases, changing the DNA in slightly different ways. There are 7 main types that need to be known.
All of these types are point mutations. A point mutation is an alteration of a single base pair within a DNA sequence. These can be classified into transition mutations and transversion mutations. Transition mutations involve changes in the chemical stability of purine (A, G) and pyrimidine (T, C) bases. Transversion (Point) mutations occur during the process of translation for protein synthesis (The Editors of Encyclopaedia Britannica , 2014).
A missense mutation is an alteration of a single base pair in the DNA sequence, resulting in change of a proteins tertiary structure due to an altered amino acid sequence, shown in Figure 14. Possibly disclosing it as non-functional (Christopher P. Austin, n.d.). Is some cases amino acids can be added to the sequence, better enabling the protein to carry out its function. This may be advantageous to the organism in terms of competition (Christopher P. Austin, n.d.). Unfortunately, in humans, missense mutations may lead to diseases/disorders such as Xeroderma pigmentosum and Cockayne’s syndrome (Suhasini AN, 2012). Xeroderma pigmentosum is a genetic disorder where DNA skin cell repair is insufficient (Genetics Home Reference, 2019). Skin damage is usually caused by ultraviolet light (UV) causing the individual to experience extreme photosensitivity. Cockayne’s syndrome is a disease responsible for premature aging and learning delay (Genetic and Rare Diseases Information Center (GARD), 2019).
A nonsense mutation is where a single base pair is altered within a DNA sequence so that is the translation process is stopped prematurely. This happens because the triplet codes for a non-coding stop codon instead of an amino acid in the transcribed mRNA (Scitable by Nature Education, 2014). This is shown in Figure 15. As a result, the protein is incomplete and is therefore not able to carry out it’s function. Diseases/Disorders associated with nonsense mutations include Duchenne Muscular Dystrophy (DMD) and Beta Thalassaemia (β-globin) (Bertoni , n.d.). DMD is a genetic disorder where the individual’s muscles undergo progressive degeneration and weakness (Muscular Dystrophy Association , n.d.). Beta Thalassaemia is a blood disorder where individuals suffer from lack of oxygen in the body due to low levels haemoglobin in the blood (Genetics Home Reference, 2019). Symptoms include yellowing in skin and whites of the eyes, misshapen bones and delayed puberty.
A silent mutation is an alteration in one base pair within the DNA sequence. Unlike other mutations the triplet still codes for the same amino acid due to the code being degenerative, shown in Figure 16. This way the proteins primary and tertiary structure is not altered and can therefore carry out its function (Annets, et al., 2016). Despite there being no change the amino acid sequence, the protein may negatively affect the efficiency and accuracy of splicing (Stylianos E. Antonarakis, 2013).
An insertion mutation is an addition of base pairs in the DNA sequence. If the number of bases inserted is a multiple of 3 than extra amino acids will be coded for, extending the protein. However, it is hazardous when the number of bases inserted is not a multiple of 3, resulting in a frameshift mutation as shown in Figure 17, (Swafford, n.d.). This causes codons in the DNA base sequence to change meaning that different amino acids will be coded for. This changes the proteins primary and tertiary structure rendering it non-functional. Insertions can cause a physical anomaly in which animals or humans have additional fingers (Kaneshiro, 2013).
A deletion mutation is a failure to copy a single nucleotide or even a whole chromosome during DNA replication (Figure 18). This results in frameshift in which the entire amino acid sequence changes. As a result, the protein’s primary and therefore tertiary structure changes, rendering the protein non-functional. Deletion mutation are responsible for genetic diseases such as Cystic Fibrosis. A disease which causes a build-up of mucus around the body (Cystic Fibrosis Trust , n.d.). It occurs when the protein which regulates movement of water and salt in cells is altered. With the respiratory system infected and cysts developing in the pancreas, individuals do not to live beyond 40 years of age (Gauthier, n.d.).
A duplication mutation is where a section of a chromosome is duplicated, shown in Figure 19. As a result, the protein may have anew function or be rendered non-functional. Despite the diseases caused, duplications are an essential part to evolution, especially in plants where whole genomes have been duplicated (Lawrence C. Brody, n.d.). However, in humans this mostly causes diseases such as cancer and Charcot-Marie-Tooth (CMT) type 1. CMT is where the individuals peripheral nerve proteins are altered due to mutations, effecting he’s/her ability to control movement and sensation (Naqvi, n.d.).
A frameshift mutation is a shift in DNA sequence as it is read by tRNA resulting in a different amino acid sequence, as shown in Figure 20. This causes the proteins tertiary structure to change which in turn renders it non-functional. These shifts are caused by the point mutations insertion and deletion which is why frameshifts are characterised as generic mutations (Scitable by nature education , n.d.). Diseases caused by frameshifts include Cancer, Crohn’s disease and cystic fibrosis, along with a lot more. Crohn’s disease is a life-long condition causes gut inflammation, more specifically in the ileum and colon area (Crohn’s and Colitis UK, n.d.). The individual experiences symptoms like abdominal pain, tiredness, fatigue and Anaemia.
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