Genes, proteins and phenotype

The relationship between genes, proteins, and an organism's observable characteristics (phenotype) is fundamental to biology. Genes act as coded instructions within DNA that dictate the production of specific proteins, which in turn determine cellular structure and function, ultimately shaping the phenotype.

• What are Genes and the Genetic Code?

  • A gene is defined as a sequence of DNA bases (or nucleotides) that codes for either a polypeptide or functional RNA.

  • The genetic code is the sequence of base triplets (codons) in mRNA that code for specific amino acids.

  • This code is universal, meaning the same specific base triplets code for the same amino acids in all living things.

  • It is also degenerate, as more than one base triplet can code for the same amino acid.

  • The code is non-overlapping, meaning each base triplet is read in sequence, separate from the triplet before and after it. Each amino acid is coded for by a sequence of three bases, called a triplet or codon.

• From Genes to Proteins (Protein Synthesis)

  • The information in DNA is used to synthesize proteins through two main stages: transcription and translation.

  • Transcription is where the DNA code of a gene is copied into messenger RNA (mRNA). In eukaryotes, this occurs in the nucleus, producing pre-mRNA, which is then spliced to remove non-coding introns, leaving only exons for the final mRNA.

  • Translation occurs in the cytoplasm, where mRNA attaches to ribosomes. Transfer RNA (tRNA) molecules carry specific amino acids to the ribosome, matching their anticodons to the mRNA codons. This process links amino acids together to form a polypeptide chain (protein).

  • The sequence of amino acids (primary structure) directly determines how the protein folds into its unique three-dimensional (3D) structure (secondary, tertiary, and quaternary). This 3D shape is crucial for the protein's specific function.

• Phenotype: Genotype and Environment

  • The phenotype of an organism is the observable characteristics resulting from the expression of its genetic constitution (genotype) and its interaction with the environment.

  • While genotype provides the potential, environmental factors like diet, disease, or temperature can influence how genes are expressed, affecting the final phenotype. For example, a plant with the genetic potential to grow tall still needs sufficient sunlight, minerals, and water to achieve that height.

• Mutations and Phenotype

  • A mutation is any change to the base (nucleotide) sequence of DNA.

  • These changes can alter the sequence of amino acids in the polypeptide a gene codes for, potentially affecting the protein's structure and function, thereby changing the phenotype.

  • Substitution mutations (one base swapped for another) may have no effect due to the degenerate nature of the genetic code, or they might change only one amino acid.

  • Deletion or insertion mutations (adding or removing bases) can cause a frameshift, altering all subsequent base triplets and usually leading to a non-functional protein.

• Examples of Gene-Phenotype Relationships:

  • Albinism: This condition results from the total or partial absence of melanin pigment, causing pale eyes, skin, and hair. It is linked to the TYR gene, which codes for the enzyme tyrosinase, essential for melanin production. A mutant TYR allele can lead to a missing or inactive tyrosinase polypeptide, thus affecting the phenotype.

  • Sickle Cell Anaemia: Caused by a mutation in the HBB gene, which codes for the beta globin polypeptide of haemoglobin. A single base substitution (GAA to GUA in DNA, leading to GAG to GUG in mRNA) results in valine being substituted for glutamic acid in the haemoglobin molecule. This changes the haemoglobin's properties, causing red blood cells to become sickle-shaped, leading to anaemia and potential vessel blockage.

  • Haemophilia: This is linked to the F8 gene, which codes for factor VIII, a blood clotting protein. A mutation in this gene can result in a missing or inactive factor VIII, affecting blood clotting.

  • Huntington's Disease: Caused by an allele of the HTT gene that includes a repeated triplet of nucleotides (a "stutter"). This mutation affects the huntingtin protein, leading to neurological symptoms.

• Gene Control (Gene Expression)

  • Not all genes in a cell are constantly expressed (transcribed and translated). This differential gene expression leads to cell specialisation, where cells develop specific structures and functions by producing a unique combination of proteins. This control ensures that only the necessary proteins are made when and where they are needed.