DNA structure, coding and protein synthesis
Inheritance, variation and evolution • Reproduction
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Nucleotides and DNA chemical units
A nucleotide consists of a sugar molecule, a phosphate group and a single base. The four DNA bases are adenine (A), thymine (T), cytosine (C) and guanine (G). Each sugar, phosphate and attached base together form one nucleotide of the DNA chain. Nucleotides join by covalent bonds between the sugar of one nucleotide and the phosphate of the next to make a long polymer. The base on each nucleotide projects from the sugar–phosphate backbone and forms hydrogen bonds with a complementary base on the opposite strand.
Double helix and base pairing
DNA in cells exists as two antiparallel strands that pair through specific base pairing: A pairs with T and C pairs with G. The paired strands coil into a double helix, with the sugar–phosphate backbones on the outside and base pairs forming the internal rungs. The double helix structure keeps the coded base sequence stable and allows copying during cell division. Complementary pairing provides a template for accurate replication and for producing complementary RNA copies during transcription.
The triplet code and amino acids
A sequence of three bases (a triplet or codon) codes for one amino acid. Three-base combinations of the four bases give 64 possible codons, which map to about 20 amino acids and stop signals. Redundancy in the code means that more than one codon can specify the same amino acid. The codon order determines the primary sequence of amino acids in the polypeptide; any change in codon sequence can change which amino acid is incorporated and therefore alter the final protein. Example codons for glycine include GGU, GGC, GGA and GGG; for alanine include GCU, GCC, GCA and GCG.
Basic protein synthesis: transcription and translation
Protein synthesis occurs in two main steps. Transcription copies the coding strand of DNA into a messenger RNA (mRNA) molecule in the nucleus. The DNA double helix locally unwinds and an enzyme builds an mRNA strand with complementary bases (U replaces T in RNA). The mRNA then exits the nucleus. Translation occurs at ribosomes in the cytoplasm. Transfer RNA (tRNA) molecules match mRNA codons to specific amino acids. Amino acids join into a polypeptide chain in the order specified by the mRNA, and the polypeptide folds into a functional protein.
How DNA changes alter proteins
A change to DNA sequence (mutation) can substitute, delete or insert bases. A single base substitution can change one codon and therefore may change one amino acid in the polypeptide. Such a single change may have little effect or may alter protein function if it affects a critical site. Insertion or deletion of bases causes a frameshift, changing every codon downstream; this typically alters many amino acids and often produces a nonfunctional protein. Mutations can therefore change protein shape and active sites, increasing, decreasing or abolishing activity.
DNA structure and the protein made
The linear sequence of bases in DNA determines the linear sequence of amino acids in a polypeptide. The chemical properties of the amino-acid sequence determine folding and the three-dimensional shape of the protein, which in turn determines function. Any change in sequence can alter folding and thus change function. Structural proteins, enzymes and hormones depend on precise amino-acid order and folding. A change in folding can alter an enzyme active site or the strength of structural proteins such as collagen.
Coding and non-coding DNA and phenotype
Coding DNA contains genes that code for proteins; non-coding DNA consists of regulatory regions, introns, repetitive sequences and other regions with variable or unknown function. Most of the human genome is non-coding. Variants in coding DNA can change protein sequence and therefore phenotype. Variants in non-coding DNA can alter gene regulation, expression levels, splicing or have neutral effects; such changes can also affect phenotype even when protein sequence remains unchanged. Forensic and identification techniques use variation in non-coding regions.
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