Genes & Protein Synthesis

A gene is a unique sequence of nucleotides on a chromosome that codes for a functional product - usually a protein, but sometimes a functional RNA molecule (tRNA, rRNA or microRNA). The fixed position of a gene on its chromosome is called its locus.

Because eukaryotic chromosomes occur in homologous pairs, most genes are present in two versions called alleles - one inherited from each parent. Alleles may be dominant or recessive, and genes may be autosomal (on chromosomes 1-22) or sex-linked (on the X or Y chromosome). An organism's genotype is fixed at fertilisation and cannot be altered, except by mutation.

THE FLOW OF GENETIC INFORMATION

In most organisms the flow of information from DNA to protein is one-directional, and it takes two steps. In the first step, called transcription, the information in a gene is copied into messenger RNA (mRNA) in the nucleus. In the second step, called translation, the information in the mRNA is used to build a protein at a ribosome in the cytoplasm.

In summary: DNA → mRNA (transcription, in the nucleus) → protein (translation, at the ribosome).

The flow of genetic information: transcription copies a gene into mRNA; translation reads the mRNA to build a protein.

RIBONUCLEIC ACID

RNA (ribonucleic acid) is the second type of nucleic acid. It serves as a temporary working copy of genetic information on its way to protein synthesis. Like DNA, each RNA nucleotide contains a sugar, a base and a phosphate group, but there are three key differences between the two molecules:

1. The sugar in RNA is ribose (not deoxyribose).
2. The base thymine (T) is replaced by uracil (U); A, G and C are unchanged.
3. RNA is usually single-stranded, whereas DNA is double-stranded.

There are several types of RNA, each with a distinct role:

• mRNA (messenger RNA) - the working copy of a gene, made during transcription; it carries the codons and has the same sequence as the coding strand of the gene (with U in place of T).
• tRNA (transfer RNA) - about 80 nucleotides folded into a clover shape, found in the cytoplasm; it carries an anticodon at one end and the matching amino acid attached at the other.
• rRNA (ribosomal RNA) - together with proteins, makes up the ribosome; the rRNA itself acts as the catalyst that joins amino acids together.
• miRNA (microRNA) - a short (about 22-base) non-coding RNA that binds complementary regions of mRNA after transcription and blocks translation - one of the cell's tools for controlling gene expression.

THE GENETIC CODE

mRNA is read in groups of three consecutive bases called codons. Each codon codes for one specific amino acid - the building blocks of proteins. With four bases available (A, U, C, G) and three bases per codon, there are 64 (= 4³) possible codons, but only 20 amino acids are used to build proteins. The code is therefore redundant: several different codons can code for the same amino acid. In addition, special codons signal where protein synthesis begins and ends: the START codon (AUG) and three STOP codons (UAA, UAG and UGA).

EXONS AND INTRONS

In eukaryotes, a gene contains coding regions called exons and non-coding regions called introns. Both are transcribed, but the introns are then removed and only the exons are translated into protein. Introns were once dismissed as junk DNA; they are now known to help regulate transcription and to code for functional RNA molecules. Most prokaryotic genes contain no introns.

TRANSCRIPTION

A sequence called the promoter marks the start of a gene - it is not transcribed itself, but it is where RNA polymerase binds. A terminator sequence marks where transcription ends. The steps of transcription are:

1. A segment of DNA is unwound, exposing the bases of the gene.
2. Free RNA nucleotides in the nucleus bind to the exposed bases of the template strand (A to U, T to A, G to C, C to G). The enzyme RNA polymerase joins these nucleotides into a growing mRNA strand.
3. The introns are removed from the immature mRNA by splicing; the exons are retained.
4. The finished mRNA leaves the nucleus through a nuclear pore, and the DNA strands rejoin behind the polymerase.

The two DNA strands have different roles. The template strand is the one actually read, in the $3'\to5'$ direction. The coding strand runs $5'\to3'$ and has the same sequence as the mRNA (with T in place of U) - the gene, as written, is the coding strand.

TRANSLATION

Translation takes place at a ribosome (rRNA plus protein) in the cytoplasm, and the mRNA is read $5'\to3$'. The steps are:

1. The mRNA binds to a ribosome, which moves along it reading codons until it reaches the START codon, AUG. The first tRNA binds, carrying the amino acid methionine - the first amino acid of every new polypeptide.
2. Each mRNA codon is bound by the complementary anticodon (also a group of three bases) of a tRNA molecule, which delivers its specific amino acid.
3. As the ribosome moves along the strand and successive codons are read, each new amino acid is joined to the previous one by a peptide bond, forming a growing polypeptide chain.
4. When a STOP codon (UAA, UAG or UGA) is reached, no tRNA matches it; translation ends and the polypeptide is released.

Translation runs from the START codon (AUG) to a STOP codon (UAA, UAG or UGA).

An mRNA codon binds the complementary anticodon of a tRNA; each codon specifies one amino acid.

USING A CODON CHART

A codon chart converts any codon into its amino acid. Find the first base of the codon along the side of the chart, the second base along the top, and use the third base to select the exact amino acid. The full conversion chain should be practised until it is mechanical.

In summary: template DNA GGT → mRNA codon CCA → tRNA anticodon GGU → amino acid proline.

Once the polypeptide leaves the ribosome it folds into its three-dimensional shape, and may undergo further post-translational processing before it can carry out its function.