Tutter A, Brodeur P, Shlomchik M, Riblet R
Medical Biology Institute, La Jolla, CA 92037.
J Immunol. 1991 Nov 1;147(9):3215-23.
We have characterized two novel mouse VH gene families, VH3609N and VHSM7. These VH families have recently diverged from previously defined VH families. The VH3609N family, which may contain only one member in most inbred strains of mice, shares sequence similarity with the VHJ606 family and is located to the 3' side of VHJ606. VHSM7, with at least three members, is related to the VHJ558 family but maps 3' of VHJ558. These findings suggest that physical displacement of VH sequences may facilitate their subsequent divergence. During the early stages of VH gene family evolution that are exemplified by these new families, amino acid replacements have been selected against in frame-work regions and selected for in complementarity-determining regions. This pattern of nucleotide substitution appears to reflect evolutionary pressures to maintain germ-line VH diversity and, possibly, to select for new antibody specificities, as well as to select against mutations resulting in aberrant Ig. The classification of VH sequences with borderline similarity to previously defined VH families is discussed.
我们已鉴定出两个新的小鼠VH基因家族，即VH3609N和VHSM7。这些VH家族最近从先前定义的VH家族中分化出来。VH3609N家族在大多数近交系小鼠中可能仅包含一个成员，与VHJ606家族具有序列相似性，位于VHJ606的3'端。VHSM7至少有三个成员，与VHJ558家族相关，但位于VHJ558的3'端。这些发现表明VH序列的物理位移可能促进其随后的分化。在以这些新家族为代表的VH基因家族进化的早期阶段，氨基酸替换在框架区域被选择淘汰，而在互补决定区域被选择保留。这种核苷酸替换模式似乎反映了维持种系VH多样性的进化压力，并且可能是为了选择新的抗体特异性，同时淘汰导致异常Ig的突变。文中还讨论了与先前定义的VH家族具有临界相似性的VH序列的分类。
