Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1

There are 10 gene families that have members on both human chromosome 6(6p21.3, the location of the human major histocompatibility complex [MHC])and human chromosome 9 (mostly 9q33-34). Six of these families also havemembers on mouse chromosome 17 (the mouse MHC chromosome) and mousechromosome 2. In addition, four of these families have members on humanchromosome 1 (1q21-25 and 1p13), and two of these have members on mousechromosome 1. One hypothesis to explain these patterns is that members ofthe 10 gene families of human chromosomes 6 and 9 were duplicatedsimultaneously as a result of polyploidization or duplication of achromosome segment ("block duplication"). A subsequent block duplicationhas been proposed to account for the presence of representatives of four ofthese families on human chromosome 1. Phylogenetic analyses of the 9 genefamilies for which data were available decisively rejected the hypothesisof block duplication as an overall explanation of these patterns. Three tofive of the genes on human chromosomes 6 and 9 probably duplicatedsimultaneously early in vertebrate history, prior to the divergence ofjawed and jawless vertebrates, and shortly after that, all four of thegenes on chromosomes 1 and 9 probably duplicated as a block. However, theother genes duplicated at different times scattered over at least 1.6billion years. Since the occurrence of these clusters of related genescannot be explained by block duplication, one alternative explanation isthat they cluster together because of shared functional characteristicsrelating to expression patterns.