Hepatitis B virus nucleotide sequences derived from a hepatocellular carcinoma with free and multiply integrated viral DNAs were determined. Based on a comparison within the X-gene region, cloned free viral DNA previously had been attributed to two distinct groups of preC minus genomes. The comparison of the complete sequence identified one of the genome equivalents as a recombinant between members of these groups. Four different integrated viral DNA elements were cloned and analysed. Similarity to either one of two DNAs representing the two groups of free viral DNA on one hand and the presence of certain mutations only on integrated DNA on the other hand, allowed to recognize distinct segments within the integrants. The data suggest a contribution of different but related genotypes to contiguous stretches of integrated viral DNA via homologous recombination. On this basis an evolutionary relationship between free and integrated DNAs of the preC and the preC minus genotype could be recognized when short sequence segments were compared. The observed coexistence on a given integrated DNA of segments homologous to free viral DNA and of segments homologous to another integrated DNA is consistent with (1) a long lasting association of individual genotypes with dividing cells and (2) multiple integration events being the result of a series of steps not separated by a long time span.

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Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.