The discovery of two closely related conserved sequences in variable-region germ-line DNA paved the way to fuller understanding of the mechanism of gene rearrangements. DNA sequencing studies revealed the presence of unique recombination signal sequences (RSSs) flanking each germ-line V, D, and J gene segment. One RSS is located 3' to each V gene segment, 5' to each J gene segment, and on both sides of each D gene segment. These sequences function as signals for the recombination process that rearranges the genes. Each RSS contains a conserved palindromic heptamer and a conserved AT-rich nonamer sequence separated by an intervening sequence of 12 or 23 base pairs (Figure 5-6a). The intervening 12- and 23-bp sequences correspond, respectively, to one and two turns of the DNA helix; for this reason the sequences are called one-turn recombination signal sequences and two-turn signal sequences.
The VK signal sequence has a one-turn spacer, and the JK signal sequence has a two-turn spacer. In X light-chain DNA, this order is reversed; that is, the VX signal sequence has a two-turn spacer, and the JX signal sequence has a one-turn spacer. In heavy-chain DNA, the signal sequences of the VH and JH gene segments have two-turn spacers, the signals on either side of the DH gene segment have one-turn spacers (Figure 5-6b). Signal sequences having a one-turn spacer can join only with sequences having a two-turn spacer (the so-called one-turn/two-turn joining rule). This joining rule ensures, for example, that a VL segment joins only to a JL segment and not to another VL segment; the rule likewise ensures that VH, DH, and JH segments join in proper order and that segments of the same type do not join each other.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.