Nucleotide sequence of the region encompassing the JC virus origin of DNA replication

Abstract

The region of the JC virus (JCV) genome from 0.58 to 0.73 map units was sequenced by the Maxam-Gilbert technique. This segment of DNA specifies several regulatory elements and the amino-terminal portion of the early viral proteins. Comparisons with the analogous regions in the polyomaviruses simian virus 40 (SV40) and BK virus (BKV) confirm the close evolutionary relationship of these three viruses. Similarities include palindromic and symmetrical sequences near their origins of DNA replication, binding sites for their large T proteins, an AT-rich region (the Goldberg-Hogness, or TATA, box), and a large tandem duplication or triplication to the late side of their replication origins (however, these sequences differ). Homology between the sequences coding for the early proteins is also evident (79 and 93 of the first 110 amino acids are shared with SV40 and BKV, respectively). Of greater interest are features of the JCV genome which differ from those of other polyomaviruses. Absent in JCV and BKV are sequences which resemble the third T-antigen binding site of SV40. In addition, a set of sequences present in JCV and BKV DNAs (33 nucleotides in JCV and 22 nucleotides in BKV) and located near a 17-base-pair palindrome shared by all three viruses is missing in SV40 DNA. Another sequence, GGGXGGAG, which is repeated several times in many polyomaviruses and adenoviruses and which is thought to play a role in DNA replication or transcription or both, is not found near the JCV origin of replication. Finally, the tandem repeat of JCV, unlike those of BKV and SV40, includes the Goldberg-Hogness sequence.