CONSERVATION OF THE ORGANIZATION OF 5 TIGHTLY CLUSTERED GENES OVER 600 MILLION YEARS OF DIVERGENT EVOLUTION

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 (Sur-1-Sur-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.