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.
Polynucleotides are made of monomeric nucleotides. DNA nucleotides are composed of a phosphate group, deoxyribose sugar, and a nitrogenous base (adenine, thymine, cytosine, or guanine). This is what genes are made of!
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.
Fig. 1 - The coding region in a segment of eukaryotic DNA
It is extremely difficult for geneticists to define just how many genes humans have. To date, scientists have identified around 22,000 genes that code for proteins and functional RNA. This discovery (which is still being added to) was possible thanks to the Human Genome Project, a remarkable international effort to sequence the human genome. Further projects, namely the Encyclopaedia of DNA Elements (ENCODE) have also embarked on determining the functions of the genes that have been discovered!
mRNA splicing
We need introns during protein synthesis because although they are important in gene expression, they are not needed when making the polypeptide. This is why messenger RNA (mRNA) splicing occurs after transcription.
mRNA splicing only occurs in eukaryotic cells as they contain introns. Prokaryotic cells do not contain introns so they don’t need mRNA splicing.
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.
Fig. 2 - The process of mRNA splicing
The specialized enzymes which catalyse mRNA splicing are called spliceosomes.
What is the genetic code?
Genes code for an amino acid sequence which, in turn, forms the polypeptide or functional RNA. But how do our cells associate a specific amino acid to a DNA base sequence? The answer is the genetic code.
The genetic code describes how codons present on mRNA molecules correspond with specific amino acids.
Codons are sequences of three nucleotides, and they are also known as triplets. These nucleotides are adenine, uracil, cytosine, and guanine. Combinations of three of these bases code for individual amino acids.
When the codons are read in succession during protein synthesis (translation), a chain of amino acids forms to build a polypeptide.
The codon CCU codes for proline and the codon ACA codes for threonine.
We usually visualize the genetic code is usually displayed as a wheel or a table.
Fig. 3 - The genetic code wheel displaying different mRNA codons
You read the codon starting from the inside out when the genetic code appears as a wheel.
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.
There are three important features of the genetic code that you need to know. The genetic code is:
- Universal
- Non-overlapping
- Degenerate
The genetic code is universal
The genetic code is the same in most organisms. This means that the CCU codon which codes for proline in humans will also code for proline in other organisms. For example, in sharks!
The genetic code is non-overlapping
It is important that each nucleotide is only part of one codon at a time and that there is no overlap. The term ‘reading frame’ refers to the start and end of the mRNA sequence and this is possible due to the start and stop codons we mentioned earlier. These codons allow the mRNA sequence to be read in a frame.
The genetic code is 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.
What are gene mutations?
Mutations are changes to a DNA base sequence. They leave us with a different codon on the mRNA strand. Most often, gene mutations arise spontaneously during DNA replication. This happens because of cellular exposure to mutagenic agents and pathogenic infections. The two types of mutations we will focus on are insertions/deletions and substitutions.
The other types of gene mutations include inversions, duplications, and translocations. Inversions occur when nucleotides swap positions within the DNA. Duplications occur when an extra copy of a gene or chromosome is produced. Translocations occur when sections of different chromosomes break off and switch places.
Insertions describe the addition of one or more unnecessary nucleotides, while deletions are the removal of one or more nucleotides.
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.
Substitutions describe the replacement of the correct nucleotide with an incorrect nucleotide.
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.
What is gene expression?
We have approximately 22,000 genes, but we don’t want all the polypeptide products express in all our cells! Gene expression controls these genes through the action of proteins called transcription factors. These transcription factors can determine whether a gene is transcriptionally active or transcriptionally silent, and therefore they regulate the type of mRNAs produced.
Our liver cells need the gene coding for alcohol dehydrogenase, which metabolizes ethanol. However, other cells like skin cells don’t need it. Therefore, the alcohol dehydrogenase gene is activated in liver cells but silenced in skin cells.
Gene expression can be regulated at the transcriptional level (the stage in which the DNA base sequence converts into a complementary mRNA strand) and at the translational level (the stage in which the mRNA strand transforms into an amino acid sequence.)
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.
Fig. 4 - The presence of specific transcription factors at the promoter site aids RNA polymerase binding
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.
At the translational level, the polypeptide produced is modified to alter its functions. This usually involves the addition of chemical groups such as lipids and phosphate groups, catalysed by specialised enzymes.
What is gene therapy?
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.
A vector is an agent that delivers a gene into a target cell.
Gene therapy research on body (somatic) cells is permitted in the UK. For example, patients suffering from severe combined immunodeficiency disease (SCID) have a faulty allele that codes for an enzyme we need for a healthy immune response, ADA. In gene therapy, a viral vector carries and delivers a normal allele for ADA into the patient’s bone marrow to synthesize functional ADA.
There is a lot of controversy surrounding gene therapy with germ line cells. Unlike somatic cells, which can only survive a limited number of mitotic divisions, germ line cells go on to produce a whole organism. This means any changes to these cells will be present in every cell of the organism. What’s more: this technology may advance to a stage where people could pick and choose which of their child’s genes they would like ‘edited.’ So, due to these ethical concerns, germ line gene therapy is illegal in the UK.
Genes - Key takeaways
- A gene is a short section of a DNA base sequence corresponding with a polypeptide. Eukaryotic genes contain exons and introns, while prokaryotic genes contain only exons.
- The genetic code describes the rules by which codons code for specific amino acids. The genetic code is universal, non-overlapping, and degenerate.
- Gene mutations are changes to the DNA base sequence. Some types of mutations include insertions, deletions, and substations.
- The regulation of gene expression is important as it determines which polypeptides are present in a cell. Regulation can occur at the transcriptional level and translational level.
- Gene therapy is an advanced technology that enables the replacement of a faulty allele with a normal allele. Research on somatic cells is permitted in the UK. However, germ line cell research is prohibited by law.
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