Composed of DNA, genes are the molecular units of heredity and are located primarily in the cell nucleus, where they are assembled into chromosomes of varying sizes. Paired chromosomes are numbered from largest (1) to smallest (22), and there are 2 additional sex chromosomes (XY or XX). The 4 bases present in DNA—adenine (A), cytosine (C), guanine (G), and thymine (T)—are combined into a double-helix structure that allows replication, transcription, and translation. The genetic structure (Fig 5-2) can be likened to the sections of an encyclopedia, with genes the chapters, exons the sentences, trinucleotides the words, and nucleotides the letters.
Mitochondria, the site of oxidative phosphorylation, are the power plants of the cell. The mitochondria are a vestige of a symbiotic relationship between 2 primitive unicellular organisms that merged to form eukaryotic organisms (most animals and plants). The fact that mitochondria still contain their own DNA is a reminder of their independent origin. Each mitochondrion contains 2–10 copies of a very short, circular segment containing 13 protein-coding genes involved in oxidative phosphorylation. Because mitochondria contain several segments of DNA and each cell contains several mitochondria, there may be variation of the mitochondrial DNA (mtDNA) within a cell and between cells of the same person, a state known as heteroplasmy. Humans acquire mitochondria from the ovum, and thus mtDNA follows maternal line inheritance.
Chromosomal DNA replication and RNA synthesis (transcription) occur within the nucleus. Messenger RNA (mRNA) is transported to ribosomes in the cytoplasm, where translation to the amino acid sequences of proteins occurs. Following the mRNA molecule’s initiation codon (start sequence) is the structural open reading frame (ORF), which is composed of exons (sequences that code for amino acids that will be present in the final protein) and introns (sequences that are spliced out during the processing of mRNA). Following the last exon is the 3' untranslated region (3' UTR). The function of this region is partly regulatory.
The development of introns in higher organisms may have had evolutionary benefits. The compartmentalization of coding segments into exons may have permitted more rapid evolution of proteins by allowing for alternative processing of precursor RNA (alternative splicing) and for rearrangements of exons during gene duplication (exon shuffling). Some introns contain complete, separate genes, and some of these may cause disease or influence the expression of other genes. Expansion of unstable repeats within introns can cause abnormal splicing and result in genetic disease. Small insertions and deletions are very common and referred to as indels.
Figure 5-2 Structures of the cell showing the location of DNA within chromosomes and mitochondria. The basic double helix of nucleotides is divided into noncoding regions, including introns and promoter regions, and coding exons, which form genes. The figure shows a noncoding intron between 2 exons. The intron is spliced out before the segment is translated. This modification occurs following transcription, though before messenger RNA (mRNA) is finalized.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.