Microbial genomes to write our history.

Received 16 March 2007; accepted 2 April 2007; electronically published 28 June 2007. Potential conflicts of interest: none reported. Reprints or correspondence: Dr. Guy de Thé, Unité d’Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France (dethe@pasteur.fr). The Journal of Infectious Diseases 2007;196:499–501 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2007/19604-0002$15.00 DOI: 10.1086/519172 The migrations of human populations are matters of great interest and hot debates in evolutionary biology, inasmuch as they relate to the rise and fall of civilizations. Multidisciplinary analyses of archeological, physical anthropological, and molecular genetic data has resulted in a near consensus view that the original human migrations out of East Africa took place some 100 thousand years ago (KYA), moving toward the middle East and then to Europe and Asia independently [1]. In contrast, Oceanic settlement via sea travel over very long distances in the myriad islands in Melanesia, Micronesia, and Polynesia in the South Pacific remain a matter of controversy and intense recent investigation [2]. Can microbiological agents, which accompanied these migrating populations as “cellular parasites,” be used as indirect but reliable markers of humans migrations [3]? We shall briefly review the data concerning 3 much-studied oncogenic agents—namely, an RNA retrovirus, a small DNA virus, and the bacterium Helicobacter pylori—as privileged markers of human migrations. Human T lymphotropic virus type 1 (HTLV-1) was initially isolated from cell cultures of a patient with an adult T cell leukemia in the United States and then in Japan. This oncogenic retrovirus was later found to be neurotropic and to be etiologically associated with a progressive degenerative neuromyelopathy called “tropical spastic paraparesis/HTLV-1–associated myelopathy” (TSP/HAM) [4]. Epidemiologically, HTLV-1 is mainly restricted to areas of endemicity such as the southern islands of the Japanese archipelago, the Caribbean region, tropical Africa, certain areas of South America, and regions of the Middle East and Melanesia. This retrovirus is transmitted through prolonged breast-feeding, sexual contact, and blood transfusion. In early 1991, our group pioneered the molecular epidemiology of HTLV-1, showing that the few genetic mutations observed in the U3 region of the HTLV-1 long terminal repeat as well as in the env gene and the Px region of a series of HTLV-1 isolates from the Ivory Coast, the Caribbean, and Japan were linked to geography but not to any associated pathology [5]. Soon after, 3 major geographical HTLV-1 genotypes were characterized: the cosmopolitan subtype A, the Central African subtype B, and the Melanesian subtype C [6, 7]. Later, a restricted subtype D was discovered in Pygmies of Central Africa. HTLV-1 exhibits high genetic stability, a quite surprising feature for a retrovirus. Such a low genetic variability appears to be linked to its replication mode, which occurs mainly during mitosis of infected lymphocytes, thus not involving reverse transcription [8]. The idea that such low genetic drift could be used as a molecular means of monitoring viral transmission and the movements of ancient human infected populations was raised in 1992 [9] and has been largely used since then for both HTLV-1 and simian T lymphotropic virus type 1 (STLV-1), which shares with HTLV-1 the same mode of replication and has similar genetic stability. The origin of most geographic HTLV1 subtypes appears to be linked to episodes of interspecies transmission between STLV1–infected monkeys and humans. However, some unanswered questions remain regarding the origin of HTLV-1 in certain areas of the world. Although it is generally accepted that the great majority of the HTLV-1 isolates from Central and South America originated via the dispersion of HTLV-1 subtype A from infected African slaves during the 16th–18th centuries, the origin of HTLV-1 cosmopolitan subtype A present in some remote Amerindian groups in the Andes remains highly debated [10]. The pathogenic HTLV1 cluster in the city of Mashadd in northern Iran also remains an enigma [11], although it is probably linked to ethnic migrations. In contrast to the human population genetics–based hypothesis of an African root for HTLV-1, the best basal clade for HTLV-1 phylogeny is to be found in the Melanesian inhabitants of the Sol-