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A series of gene duplications that began in a stem species of Mammalia and led to five developmentally regulated hemoglobin beta-chain loci (epsilon, gamma, eta, delta, and beta) in a common ancestor of eutherian orders Artiodactyla, Rodentia, Lagomorpha, and Primates had important consequences in mammalian evolution. Findings reported here indicate that two progenitors of the five linked genes existed by the time of the eutherian (placental mammal)-metatherian (marsupial mammal) split and that these two genes were already differentiated with respect to their promoter regions and developmental expression. Southern blot and sequence analyses of the hemoglobin beta-chain genes of the opossum (Didelphis virginiana) revealed only two genes, one with coding and promoter sequences similar to eutherian prenatally expressed epsilon, gamma, and eta genes and the other coding for adult opossum hemoglobin beta-chains and having eutherian adult beta-type promoters. The most parsimonious arrangement of greater than 80 beta-globin exon sequences depicts the opossum embryonic-type gene as orthologously related to eutherian epsilon, gamma, and eta genes and the opossum adult-type gene as orthologously related to delta and beta genes. These data further indicate that after the initial beta duplication in the stem of Mammalia, the locus that became developmentally delayed in its expression evolved at a faster rate than the locus that became embryonically expressed.

Evolutionary and developmental aspects of two hemoglobin beta-chain genes (epsilon M and beta M) of opossum.