The Order of Nitrogenous Bases in DNA Determines Protein Order

DNA carries the instructions for building proteins, essential for nearly all cellular functions. These instructions are encoded in a specific sequence of nitrogenous bases—adenine (A), thymine (T), cytosine (C), and guanine (G). The order of these bases determines how amino acids are assembled into proteins, shaping their structure and function.

Key Components Of Base Pairing

DNA’s structure relies on precise nitrogenous base pairing, ensuring genetic information is accurately stored and transmitted. Complementary base pairing dictates that adenine (A) always pairs with thymine (T), while cytosine (C) pairs with guanine (G). These pairings are stabilized by hydrogen bonds—A-T pairs form two hydrogen bonds, while C-G pairs establish three, making them more stable. This arrangement maintains the uniform width of the DNA double helix, first elucidated by Watson and Crick in 1953.

Purines (A and G) are larger, double-ringed molecules, whereas pyrimidines (T and C) are smaller, single-ringed structures. Pairing a purine with a pyrimidine ensures a consistent helical diameter, preventing distortions that could compromise DNA integrity. The strands are antiparallel, with one running 5′ to 3′ and the other 3′ to 5′, a critical orientation for replication and transcription. DNA polymerase relies on this alignment to synthesize new strands.

Base pairing also aids error correction. DNA polymerase possesses proofreading capabilities, detecting and excising mismatched bases during replication. Its exonuclease activity reduces the error rate to approximately one mistake per billion base pairs. However, environmental factors like UV radiation or chemical mutagens can introduce errors by disrupting hydrogen bonding, leading to mutations that may alter genetic expression.

Translating The Sequence Into Amino Acids

The nitrogenous base sequence in DNA dictates amino acid arrangement in proteins. Transcription begins this process, where RNA polymerase copies a DNA segment into messenger RNA (mRNA). Unlike DNA, mRNA contains uracil (U) instead of thymine (T). The mRNA strand carries genetic instructions from the nucleus to the ribosome, the site of protein synthesis.

At the ribosome, the nucleotide sequence is read in sets of three bases, or codons. Each codon specifies an amino acid or a regulatory signal, such as a start or stop command. The genetic code, nearly universal across all organisms, includes 64 codons encoding 20 amino acids. Redundancy in the code ensures that some mutations have minimal impact. For example, both GAA and GAG code for glutamic acid, so a mutation in the third position might not affect the protein.

Transfer RNA (tRNA) molecules decode mRNA by delivering amino acids to the ribosome. Each tRNA has an anticodon complementary to a specific mRNA codon, ensuring correct amino acid incorporation. Aminoacyl-tRNA synthetases attach amino acids to tRNAs with remarkable specificity, achieving error rates as low as one in 10,000. This precision is crucial for proper protein formation and function.

Formation Of Polypeptide Chains

As the ribosome moves along the mRNA strand, amino acids are linked by peptide bonds, forming a polypeptide chain. The ribosome’s larger subunit catalyzes bond formation, while the smaller subunit ensures accurate codon-anticodon pairing. The polypeptide extends directionally from the amino (N) terminus to the carboxyl (C) terminus.

Elongation factors assist in tRNA positioning and ribosome movement, enhancing translation speed while minimizing errors. Ribosomes in eukaryotic cells can add up to ten amino acids per second, maintaining a balance between speed and accuracy. Guanosine triphosphate (GTP) provides the necessary energy for elongation.

As the polypeptide grows, it begins folding into its functional three-dimensional shape, guided by molecular chaperones. These specialized proteins stabilize intermediate structures, preventing misfolding. Some polypeptides undergo post-translational modifications, such as phosphorylation or glycosylation, which influence stability, localization, and interactions with other cellular components.

Mutations That Alter Nucleotide Order

Changes in the nitrogenous base sequence can disrupt genetic instructions, affecting protein structure and function. Mutations may occur spontaneously during DNA replication or result from environmental factors like radiation or chemical exposure. Depending on the mutation type, the resulting protein may be nonfunctional, partially functional, or gain a new function.

Point Mutations

A point mutation involves the substitution of a single nucleotide. Silent mutations occur when the change does not alter the amino acid due to genetic code redundancy. Missense mutations result in a different amino acid, potentially affecting protein stability or function. Sickle cell disease, caused by a single nucleotide substitution in the HBB gene, leads to abnormal hemoglobin production. Nonsense mutations introduce a premature stop codon, truncating the protein and often rendering it nonfunctional. The severity depends on the mutation’s location, with those occurring earlier in the gene typically having greater effects.

Insertions

Insertion mutations add one or more nucleotides to the DNA sequence, potentially disrupting the reading frame. Frameshift mutations alter codon grouping, leading to an entirely different amino acid sequence. This often results in nonfunctional proteins due to extensive missense regions or premature stop codons. Insertion mutations in the FMR1 gene are associated with Fragile X syndrome, a genetic disorder affecting cognitive development. Repetitive sequence insertions increase genetic instability, and larger insertions may disrupt entire genes or regulatory regions, significantly impacting cellular function.

Deletions

Deletions remove one or more nucleotides, potentially causing frameshift mutations if the number of deleted bases is not a multiple of three. This alters the downstream amino acid sequence, often resulting in a nonfunctional protein. Duchenne muscular dystrophy, caused by deletions in the DMD gene, eliminates functional dystrophin, leading to progressive muscle degeneration. Some deletions remove entire exons, affecting critical protein domains. While small deletions may have minimal effects, larger deletions can eliminate essential coding regions, leading to severe genetic disorders. The impact depends on size, location, and whether regulatory elements essential for gene expression are affected.