Arrangement of DNA: The process by which immunoglobulins (antibodies) are produced by B lymphocytes involves permanent rearrangements of the DNA in these cells. The immunoglobulins (for example, IgG) consist of two light and two heavy chains, with each chain containing regions of variable and constant amino acid sequence. The variable region is the result of somatic recombination of segments within both the light-and the heavy-chain genes. During B-lymphocyte development, single variable (V), diversity (D), and joining (J) gene segments are brought together through gene rearrangement to form a unique variable region (Fig. 33.18). This process allows the generation of 109−1011 different immunoglobulins from a single gene, providing the diversity needed for the recognition of an enormous number of antigens. [Note: Pathologic DNA rearrangement is seen with translocation, a process by which two different chromosomes exchange DNA segments.] 4.
Mobile DNA elements: Transposons (Tn) are mobile segments of DNA that move in an essentially random manner from one site to another on the same or a different chromosome. Movement is mediated by transposase, an enzyme encoded by the Tn itself. Movement can be direct, in which transposase cuts out and then inserts the Tn at a new site, or replicative, in which the Tn is copied and the copy inserted elsewhere while the original remains in place. In eukaryotes, including humans, replicative transposition frequently involves an RNA intermediate made by a reverse transcriptase (see p. 424), in which case the Tn is called a retrotransposon. Transposition has contributed to structural variation in the genome but also has the potential to alter gene expression and even to cause disease. Tn comprise ~50% of the human genome, with retrotransposons accounting for 90% of Tn. Although the vast majority of these retrotransposons have lost the ability to move, some are still active. Their transposition is thought to be the basis for some rare cases of hemophilia A and Duchenne muscular dystrophy. [Note: The growing problem of antibiotic-resistant bacteria is a consequence, at least in part, of the exchange of plasmids among bacterial cells. If the plasmids contain Tn-carrying antibiotic resistance genes, the recipient bacteria gain resistance to one or more antimicrobial drugs.]
V. CHAPTER SUMMARY