Multiple MSP pseudogenes in a local repeat cluster on 1p36.2: An expanding genomic graveyard?

Chromosomal region 1p36.2 harbors an intriguing gene cluster of about 1 Mb. In addition to normal high-copy-number repeats, this cluster consists entirely of locally repeated sequences among which there are tRNA and small nuclear RNA (snRNA) genes. In 23 PACs and YACs from the 1p36.2 cluster, we identified eight different copies of a sequence with about 97% homology to the macrophage stimulating protein (MSP) gene located on chromosomal band 3p21. These MSP-like (MSPL) sequences on 1p36.2 are scattered over the repeat region. Nucleotide substitutions and single nucleotide deletions in exons of all identified MSPL genes on 1p36.2 mark them as pseudogenes. We constructed a phylogenetic tree of these sequences with their most likely order of origin in evolution. MSP from 3p21 could be identified as the ancestral sequence, a copy of which was captured into the cluster of tRNA and snRNA genes on 1p36.2 about 6 million years (MY) ago. MSP subsequently coamplified with the other sequences in the cluster. Analysis of the DNA of 18 individuals shows that the MSPL copy number is polymorphic, with a range of four to seven or more copies per haploid genome. Analysis of corresponding clusters in macaque chromosomes indicated an age for the tRNA/snRNA cluster of at least 30 MY. The MSPL sequence thus functions as a probe for the more recent primate evolution of this cluster and suggests a continuation of its unusual activity over the last 6 MY.