The mouse surfeit locus is an unusually tight cluster of at least six ''housekeeping'' genes that do not share any sequence homology and whose gene organization may play a role in gene expression. The transcription of each of the five well-characterized genes (Surf-1 to -5) alternates with respect to its neighbor(s) and no more than 159 bp separates any two adjacent genes with the Surf-4 and Surf-2 genes overlapping at their 3' ends by 133 bp. In this work, the expression of the Surf-5 and Surf-4 genes has been examined in various mouse tissues. In addition to the ubiquitously expressed 3.5-kb Surf-5 mRNA, a second alternatively spliced Surf-5 mRNA, Surf-5b, was discovered that was highly expressed in the brain, heart, testis, and skeletal muscle. The alternative splice donor site of the Surf-5b mRNA is similar to splice donor sites found in neuron-specific mRNAs. Surf-5b encodes a unique protein, which, like the ubiquitous Surf-5 protein, has been found to be primarily located in the soluble fraction of the cytoplasm. The expression of the Surf-5b protein was also found to increase in embryonal carcinoma cells differentiated into neuronal cultures. Although the Surf-5 gene is highly conserved through evolution, the presence of the Surf-5b alternative splice may be restricted to higher vertebrates. The Surf-4 gene was ubiquitously expressed in eight different mouse tissues; however, the ratios of the three previously reported Surf-4 mRNAs (two of which are known to derive from different sites of polyadenylation) altered dramatically between tissues. The use of different forms of mRNA processing for regulation of tissue-specific expression of ubiquitously expressed genes is discussed.

The four previously characterized genes (Surf1to4) of the mouse Surfeit locus do not share any sequence homology, and the transcription of each gene alternates with respect to its neighbor(s). Adjacent Surfeit genes are separated by very small distances, and two of the genes overlap at their 3′ ends. In this work we have further defined the Surfeit gene cluster by the isolation ofSurf5,a fifth gene of the locus, and determination of its relationship to the other Surfeit genes.Surf5does not share any sequence homology with the four cloned Surfeit genes. The transcription ofSurf5is divergent with respect to its neighbor theSurf3gene, and the 5′ ends ofSurf5andSurf3are separated by only 159 bp, suggesting the presence of a second bidirectional promoter in the locus. The 3′ end ofSurf5maps only 68 bp away from the processed 3′ end of a pseudogene. The human and partial chickenSurf5coding regions show greater than 95% identity, and aCaenorhabditis eleganshomologue shows 38% identity and 56% similarity with the mouseSurf5amino acid sequence. The 3.5-kb transcript ofSurf5encodes a small hydrophilic protein of 140 amino acid residues, which differs from the ribosomal protein L7a encoded by theSurf3gene or the integral membrane protein encoded by theSurf4gene. Subcellular fractionation located theSurf5protein to the soluble fraction of the cytoplasm. The Surfeit locus appears to represent a novel type of gene cluster in which the genes are unrelated by sequence or function; however, their organization may play a role in their gene expression.

The mouse Surfeit locus contains an unusually tight cluster of six housekeeping genes (Surf-1 to -6) which are unrelated by sequence homology. Using a mouse Surfeit locus probe, a 16 kb clone has been isolated which contains the human Surf-1 and Surf-3 genes and regions of the human Surf-2 and Surf-5 genes. The organization and juxtaposition of these human Surfeit locus genes are the same as found in the mouse. Using the human clone as a biotinylated probe for fluorescence in situ hybridization (FISH) we have confirmed the location of the human Surfeit locus to chromosome band 9q34. Metaphase spreads of human chronic myeloid leukemic cells containing the t(9;22)(q34;q11) translocation involving The c-abl gene at 9q34.1 an acute nonlymphocytic leukemic cells containing the t(6;9)(q34;p23) translocation involving the can gene at 9q34.1 were analyzed by FISH using the human Surfeit clone as a probe. These analyses locate the human Surfeit locus telomeric to the c-abl and can genes at chromosome band 9q34.1.

The organization of the mouse surfeit locus is unusual in that it contains six housekeeping genes (Surf-1-Surf-6), which are unrelated by sequence homology, in the tightest mammalian gene cluster thus far described. A maximum of only 73 base pairs separates any two of the four well-characterized genes, and two of the genes overlap at their 3' ends. The direction of transcription of each of the five surfeit genes, Surf-1-Surf-5, alternates with respect to that of its neighbor, suggesting cis-interaction or coregulation between the genes by mechanisms such as the sharing of regulatory elements and/or antisense regulation. The Surf-3 gene has been identified as encoding the ribosomal protein L7a (Rpl7a). We have used the high conservation of the Rpl7a gene to clone the chicken gene and surrounding genomic DNA. The tight clustering and juxtaposition of at least five of the surfeit genes (Surf-1-Surf-5) and their associated CpG-rich islands have been found to be conserved over the 600 million years of divergent evolution that separates birds and mammals. This strongly suggests that the surfeit locus represents a different form of gene cluster in which gene organization may play both a positive and negative regulatory role in gene expression possibly via cis-interactions between the closely spaced genes.