The Navaho and Flathead people in the continental United States and the Chamorro of Guam excrete JCV at a signifi- cantly higher frequency than do populations of European origin. The excretion rates in all populations studied to date (40 – 69%) make it practical to determine the genotype of JCV harbored by ethnic groups in any part of the world.
All three indigenous cohorts excreted predominantly strains of JCV type 2A, the genotype that is characteristic of China and Japan (6, 16). type 2B is a related subtype that comprises a minor group of strains in the United States and that presumably arrived with European settlers. Its actual distri- bution and prevalence in Europe is still unknown. Among 25 JCV strains obtained in Hungary, all were type 1. We have included the minor variant designated type 2C within the type 2A group. Among the Navaho, the occurrence of JCV type 2A 2C was 4246 (91%). Among the Flathead people, where there has been considerable intermarriage with the surround- ing Caucasian population (10), the occurrence of JCV type 2A 2C was 1116 (69%). This compares to an occurrence of type 2A 2C in the control population of the United States of only 23%. The strains of JCV in Native Americans appear to be very closely related to those of China and Japan. These Native American strains have changed very little from the presumed parental Northeast Asian strains. The complete genome of the Japanese prototype type 2A strain, termed Tokyo-1, differs from the Navaho type 2A or type 2C strains by only 0.31– 0.45%. This is less than the 0.5–1.0% difference that presump- tively defines different subtypes of JCV (7). In contrast, the major genotypes of the virus differ by about 1.0–2.5% in their genomic DNA sequence. The fact that these Asian strains have changed so little since ancestors of the Navaho migrated across the Bering land bridge in the late Pleistocene suggests roughly the timing of JCV genotype evolution. The arrival of these first American settlers has been dated by artifacts at prehistoric sites to between 12,000 and 30,000 years ago. The close relationship of Navaho strains to JCV (Tokyo-1) pushes the time of origin of the major JCV genotypes in humans to well before the time of arrival of the first Americans. Because JCV had already differentiated into stable modern genotypes by that time, the origin of JCV in humans probably dates from 50,000 to 100,000 years ago or more. If so, it would appear that JCV may have coevolved with modern humans (Homo sapiens sapiens).
JCV strains from the Chamorro of Guam have not yet been sequenced in their entirety, and it is uncertain whether they represent a distinct subtype of type 2. Nevertheless, they clearly represent a variant of type 2A, in which ‘‘A’’ at position 1805 is consistently replaced by ‘‘T’’ in the Chamorro strains. The existence of this variant on Guam likely reflects the origins of the indigenous Chamorro population, although Spanish and Filipino influence have also occurred in the more recent past. Interestingly, the type 2A variant (‘‘T’’ at 1805) identified in Guam has also been discovered in the urine of a 43-year-old HIV-positive male Filipino living in Los Angeles (unpublished data). This raises the possibility that JCV strains in Micronesia and the Philippines may have a common ancestor. Further, by this criterion the Navaho strains are more closely related to type 2A from Japan (represented by Tokyo-1) than they are to the Asian Pacific (Chamorro) strains. A final determination awaits analysis of the entire sequence of the Chamorro variant of JCV. It will be of interest to characterize the major JCV genotypes in other Pacific populations (especially Australo- Melanesian and Polynesian groups) in relation to the Asian, Native American, and Micronesian strains.
For a viral marker to be useful for following both early and recent worldwide population movements, it is necessary that it have evolved early, and it is desirable that it be ubiquitous. Moreover, it should be quite stable genetically and should be transmitted largely within the family or the immediate com- munity. JCV is a DNA virus that appears to meet these essential requirements. Like mitochondrial DNA, JCV has evolved relatively rapidly compared with the human genome, yet unlike many highly infectious RNA viruses, its genomic sequence has not changed so rapidly that ancient associations are lost. Other viruses that may have coevolved with human- kind and that may serve as markers for early and recent human migrations include retroviruses with unusually high genomic stability such as HTLV-1 (17, 18) and DNA viruses such as the human papillomaviruses (HPV) (19). …. Interestingly, like JCV, variants of HPV-16 show African, East Asian, and European associations (19). Information about the human diaspora obtained from viruses that coevolved with branches of the human family tree should correlate with that provided by genetic, archeologic, and linguistic data (20).
In summary, the simplicity of the distribution of the three main genotypes of JCV in Europe (type 1), Asia (type 2), and Africa (types 3 and 6) suggests a coincidence of viral evolution with the major lineages of early humans who migrated out of their probable ancestral home in Africa to people the conti- nents of Asia and Europe around 100,000 years ago. The close relationship of JCV found today in Native Americans with that in Northeast Asia, and its distinction from Micronesian strains, is consistent with the migration of Amerind ancestors from Northeast Asia by way of the Bering land bridge. Further detailed study of JCV genomes from indigenous North, Cen- tral, and South American populations might identify variant viral genomes that mark successive waves of immigration to the New World.
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