133. Differential Expansion of Homologous Zinc-Finger Gene Families in Human Chromosome 19q13.2 and Mouse Chromosome 7 

Mark Shannon¹, Elbert Branscomb¹, Loren Hauser², Anne Olsen¹, Laurie Gordon¹, Linda K. Ashworth¹, and Lisa Stubbs^1 
1Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, P.O. Box 808, L-452, Livermore, CA 94550 and ²Life Sciences Division, Oak Ridge National Laboratory, P.O. Box 2009, Oak Ridge, TN 37831 
shannon8@llnl.gov 
 

Mapping studies indicate that many of the 600-1000 mammalian zinc-finger (ZNF)-containing genes reside within familial clusters, particularly those genes encoding Kruppel-associated box (KRAB) motifs. However, little is known about family content, organization, or evolutionary conservation. In previous studies, we identified and characterized homologous KRAB-containing ZNF gene families located in human chromosome 19q13.2 and mouse chromosome 7. Here we present details of the construction and characterization of contigs that completely span these families. The human cluster spans 700kb and is comprised of 16 members that are arrayed in tandem. By contrast, the mouse family spans approximately 400kb and contains just 10 genes. We have also identified cDNA clones corresponding to each family member and have analyzed their sequences. The KRAB A domains encoded by the human and mouse genes are highly similar in sequence, but other portions of the predicted proteins encoded by the clustered paralogs may be more divergent in structure. To predict the evolutionary relationships between genes within and between the families, ZNF-containing regions were compared using computational methods. These studies uncovered three pairs of putative orthologs, but also provided evidence for the continued evolution of the families in both species after their divergence from a common ancestor. Recent evolutionary events include intragenic ZNF repeat alterations as well as complete gene duplications. These studies therefore expose complex, yet discernible, histories of sequence duplication and divergence and pave the way for studies of the evolution of gene function within the related families.