Genes

A gene is a short section of a DNA base sequence that corresponds with the ‘code’ needed to make a polypeptide (like proteins or RNA.) These polypeptides (not to be confused with polynucleotides, which is what DNA is) are made of a long chain of amino acids joined by peptide bonds. The types of proteins that result include enzymes, hormones, and antibodies. The types of RNAs that are made include transfer RNA (tRNA) and ribosomal RNA (rRNA), which are required for protein synthesis.

Eukaryotic genes

Eukaryotic genes are slightly different from prokaryotic genes as they contain regions called exons and introns. Exons are the coding regions of DNA: they are the base sequences that hold the code needed to form the polypeptide. On the flip side, introns are the non-coding regions: they don’t code for an amino acid sequence. Many textbooks refer to these introns as ‘junk’ DNA but they are very important sites for regulating gene expression.

Transcription is the process of transferring the DNA base sequence of a gene onto a complementary mRNA strand. This is the first step in protein synthesis and it happens in the nucleus. Remember, genes are composed of both exons and introns so the mRNA strand will also contain both (some textbooks refer to this as pre-mRNA.) Introns are unwanted for protein synthesis, so specialised enzymes excise the RNA sequence corresponding with the intron and this allows the exons to join together. This leaves us with an mRNA strand containing only coding regions which correspond with an amino acid sequence.

A polypeptide molecule has a start and an end, so how does protein synthesis know when to begin and finish? This happens thanks to start and stop codons. As their name suggests, start codons initiate translation and mark the beginning of the polypeptide. This codon is AUG in most organisms, which codes for the amino acid methionine. As the protein reads the codons, it eventually reaches a stop codon, which terminates the elongation of the polypeptide. The genetic code features three stop codons: UGA, UAG, and UAA. Unlike the other codons, they do not code for an amino acid.

• Universal
• Non-overlapping
• Degenerate

This feature describes how some amino acids can correspond to more than one codon. As there are 4 different types of nucleotides, there are a total of 64 combinations of codons. But there are only 20 amino acids. This shows us that many codons can code for the same amino acid, and you can clearly see this in the genetic code wheel.

These events cause a frameshift mutation. This means that every codon following the mutation will change, effectively ‘shifting’ the reading frame. As you can see, adding or removing even just one nucleotide significantly changes the DNA sequence and, consequently, the polypeptide to be synthesized. This usually harms the organism.

For example, the triplet CCA codes for the amino acid proline. If a substitution occurs and the triplet changes to CGA, an entirely new amino acid called arginine is coded for instead. However, this is not always the case. If CCA were to mutate into CCG, both triplets correspond to proline due to the degenerate nature of the genetic code. This type of substitution mutation does not affect the polypeptide and therefore has a neutral effect on the organism.

At the transcriptional level, transcription factors regulate which genes are ‘on’ and ‘off’ by assisting the binding of RNA polymerase to the promoter region on the gene. The promoter is located in the gene and is the spot where RNA polymerase must bind for transcription to be initiated. There are two types of transcription factors: activators and repressors. Activators bind RNA polymerase to the promoter site to activate transcription. Conversely, repressors inhibit the binding of RNA polymerase, thereby silencing the gene’s transcription.

Epigenetics also plays a big role in gene expression. This involves changes to a structure called the ‘DNA-histone complex.’ This complex helps DNA fit inside the nucleus, and it is made of DNA wound around proteins called histones. When the DNA is tightly wound around the histones, RNA polymerase cannot access the promoter, repressing transcription. When the DNA-histone complex is in this form, it is also called heterochromatin. Another form called euchromatin involves DNA loosely wound around the histones, allowing RNA polymerase to bind to the promoter and activate transcription.

Gene therapy means removing a faulty allele and replacing it with a healthy one. This type of treatment is done on patients with genetically caused diseases like haemophilia and myelomas. Doctors use viral vectors, as these agents carry the normal alleles and infect the cell, enabling the alleles to be delivered into the nucleus. The allele will be transcribed and translated to produce the functional protein using the patient’s protein synthesis machinery.