How Gene Mutation Works

Genes are segments of DNA located on chromosomes. A gene mutation is defined as an alteration in the sequence of nucleotides in DNA. This change can affect a single nucleotide pair or larger gene segments of a chromosome. DNA consists of a polymer of nucleotides joined together. During protein synthesis, DNA is transcribed into RNA and then translated to produce proteins. Altering nucleotide sequences most often results in nonfunctioning proteins. Mutations cause changes in the genetic code that lead to genetic variation and the potential to develop disease. Gene mutations can be generally categorized into two types: point mutations and base-pair insertions or deletions.

Point Mutations

Point mutations are the most common type of gene mutation. Also called a base-pair substitution, this type of mutation changes a single nucleotide base pair. Point mutations can be categorized into three types:

• Silent Mutation: Although a change in the DNA sequence occurs, this type of mutation does not change the protein that is to be produced. This is because multiple genetic codons can encode for the same amino acid. Amino acids are coded for by three nucleotide sets called codons. For example, the amino acid arginine is coded for by several DNA codons including CGT, CGC, CGA, and CGG (A = adenine, T = thymine, G = guanine and C = cytosine). If the DNA sequence CGC is changed to CGA, the amino acid arginine will still be produced.
• Missense Mutation: This type of mutation alters the nucleotide sequence so that a different amino acid is produced. This change alters the resulting protein. The change may not have much effect on the protein, may be beneficial to protein function, or may be dangerous. Using our previous example, if the codon for arginine ​CGC is changed to GGC, the amino acid glycine will be produced instead of arginine.
• Nonsense Mutation: This type of mutation alters the nucleotide sequence so that a stop codon is coded for in place of an amino acid. A stop codon signals the end of the translation process and stops protein production. If this process is ended too soon, the amino acid sequence is cut short and the resulting protein is most always nonfunctional.

Base-Pair Insertions/Deletions

Mutations can also occur in which nucleotide base pairs are inserted into or deleted from the original gene sequence. This type of gene mutation is dangerous because it alters the template from which amino acids are read. Insertions and deletions can cause frame-shift mutations when base pairs that are not a multiple of three are added to or deleted from the sequence. Since the nucleotide sequences are read in groupings of three, this will cause a shift in the reading frame. For example, if the original, transcribed DNA sequence is CGA CCA ACG GCG..., and two base pairs (GA) are inserted between the second and third groupings, the reading frame will be shifted.

• Original Sequence: CGA-CCA-ACG-GCG...
• Amino Acids Produced: Arginine - Proline - Threonine - Alanine...
• Inserted Base Pairs (GA): CGA-CCA-GAA-CGG-CG...
• Amino Acids Produced: Arginine - Proline - Glutamic Acid - Arginine...

The insertion shifts the reading frame by two and changes the amino acids that are produced after the insertion. The insertion can code for a stop codon too soon or too late in the translation process. The resulting proteins will be either too short or too long. These proteins are for the most part defunct.

Causes of Gene Mutation

Gene mutations are most commonly caused as a result of two types of occurrences. Environmental factors such as chemicals, radiation, and ultraviolet light from the sun can cause mutations. These mutagens alter DNA by changing nucleotide bases and can even change the shape of DNA. These changes result in errors in DNA replication and transcription.

Other mutations are caused by errors made during mitosis and meiosis. Common errors that occur during cell division can result in point mutations and frameshift mutations. Mutations during cell division can lead to replication errors which can result in the deletion of genes, translocation of portions of chromosomes, missing chromosomes, and extra copies of chromosomes.

Genetic Disorders

According to the National Human Genome Institute, most all disease have some sort of genetic factor. These disorders can be caused by a mutation in a single gene, multiple gene mutations, combined gene mutation and environmental factors, or by chromosome mutation or damage. Gene mutations have been identified as the cause of several disorders including sickle cell anemia, cystic fibrosis, Tay-Sachs disease, Huntington disease, hemophilia, and some cancers.

Source

National Human Genome Research Institute

Dissecting the Genetic Code

 Genetic Code Table. Darryl Leja, NHGRI

The genetic code is the sequence of nucleotide bases in nucleic acids (DNAand RNA) that code for amino acidchains in proteins. DNA consists of the four nucleotide bases: adenine (A), guanine (G), cytosine (C) and thymine (T). RNA contains the nucleotides adenine, guanine, cytosine and uracil (U). When three continuous nucleotide bases code for an amino acid or signal the beginning or end of protein synthesis, the set is known as a codon. These triplet sets provide the instructions for the production of amino acids. Amino acids are linked together to form proteins.

Codons

RNA codons designate specific amino acids. The order of the bases in the codon sequence determines the amino acid that is to be produced. Any of the four nucleotides in RNA may occupy one of three possible codon positions. Therefore, there are 64 possible codon combinations. Sixty-one codons specify amino acids and three (UAA, UAG, UGA) serve as stop signals to designate the end of protein synthesis. The codon AUG codes for the amino acid methionine and serves as a start signal for the beginning of translation. Multiple codons may also specify the same amino acid. For example, the codons UCU, UCC, UCA, UCG, AGU, and AGC all specify serine. The RNA codon table above lists codon combinations and their designated amino acids. Reading the table, if uracil (U) is in the first codon position, adenine (A) in the second, and cytosine (C) in the third, the codon UAC specifies the amino acid tyrosine. The abbreviations and names of all 20 amino acids are listed below.

Amino Acids

Ala: Alanine               Asp: Aspartic acid    Glu: Glutamic acid    Cys: Cysteine
Phe: Phenylalanine   Gly: Glycine          His: Histidine            Ile: Isoleucine
Lys: Lysine                Leu: Leucine           Met: Methionine       Asn: Asparagine
Pro: Proline               Gln: Glutamine        Arg: Arginine            Ser: Serine
Thr: Threonine          Val: Valine               Trp: Tryptophan        Tyr: Tyrosine

Protein Production

Proteins are produced through the processes of DNA transcription and translation. The information in DNA is not directly converted into proteins, but must first be copied into RNA. DNA transcription is the process in protein synthesis that involves the transcribing of genetic information from DNA to RNA. Certain proteins called transcription factors unwind the DNA strand and allow the enzyme RNA polymerase to transcribe only a single strand of DNA into a single stranded RNA polymer called messenger RNA (mRNA). When RNA polymerase transcribes the DNA, guanine pairs with cytosine and adenine pairs with uracil.

Since transcription occurs in the nucleus of a cell, the mRNA molecule must cross the nuclear membrane to reach the cytoplasm. Once in the cytoplasm, mRNA along with ribosomes and another RNA molecule called transfer RNA, work together to translate the transcribed message into chains of amino acids. During translation, each RNA codon is read and the appropriate amino acid is added to the growing polypeptide chain. The mRNA molecule will continue to be translated until a termination or stop codon is reached.

Mutations

A gene mutation is an alteration in the sequence of nucleotides in DNA. This change can affect a single nucleotide pair or larger segments of a chromosomes. Altering nucleotide sequences most often results in non-functioning proteins. This is because changes in the nucleotide sequences change the codons. If the codons are changed, the amino acids and thus the proteins that are synthesized will not be the ones coded for in the original gene sequence. Gene mutations can be generally categorized into two types: point mutations and base-pair insertions or deletions. Point mutations alter a single nucleotide. Base-pair insertions or deletions result when nucleotide bases are inserted into or deleted from the original gene sequence. Gene mutations are most commonly the result of two types of occurrences. First, environmental factors such as chemicals, radiation, and ultraviolet light from the sun can cause mutations. Secondly, mutations may also be caused by errors made during the division of the cell (mitosisand meiosis).