Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence

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Abstract
The complete nucleotide sequence of a woodchuck hepatitis virus genome cloned in Escherichia coli was determined by the method of Maxam and Gilbert. This sequence was 3308 nucleotides long. Potential ATG initiator triplets and nonsense codons were identified and used to locate regions with a substantial coding capacity. A striking similarity was observed between the organization of human hepatitis B virus and woodchuck hepatitis virus. Nucleotide sequences of these open regions in the woodchuck virus were compared with corresponding regions present in hepatitis B virus. This allowed the location of 4 viral genes on the long strand and indicated the absence of protein coded by the short strand. Evolution rates of the various parts of the genome and of the 4 different proteins coded by hepatitis B virus and woodchuck hepatitis virus were compared. Evidently, the core protein has evolved slightly less rapidly than the other patients, and when a region of DNA codes for 2 different proteins, there is less freedom for the DNA to evolve and 1 of the proteins can evolve more rapidly than the other. A hairpin structure, very well conserved in the 2 genomes, was located in the only region devoid of coding function, suggesting the location of the origin of replication of the viral DNA.