MBE Advance Access originally published online on January 22, 2004
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Mol. Biol. Evol. 21(3):603-611. 2004
DOI: 10.1093/molbev/msh053
© 2004 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038
The Low Evolutionary Rate of Human T-Cell Lymphotropic Virus Type-1 Confirmed by Analysis of Vertical Transmission Chains
* Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Department of Zoology, University of Oxford, Oxford, U.K.
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
Université Catholique de Louvain, Unité de Virologie, Bruxelles, Belgium
| Hospital San Roque, San Salvador de Jujuy, Argentina
¶ Laboratoire de Rétrovirologie, Institut Pasteur de la Guyane, Cayenne, French Guiana
# Instituto de Medicina Tropical ‘Alexander Von Humboldt’, Universidad Peruana Cayetano Heredia, Lima, Peru
** Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Bahia School of Medicine and Public Health, Salvador, Bahia, Brazil
E-mail: Sonia.VanDooren{at}uz.kuleuven.ac.be.
The evolutionary rate of the human T-cell lymphotropic virus type-1 (HTLV-1) is considered to be very low, in strong contrast to the related human retrovirus HIV. However, current estimates of the HTLV-1 rate rely on the anthropological calibration of phylogenies using assumed dates of human migration events. To obtain an independent rate estimate, we analyzed two variable regions of the HTLV-1 genome (LTR and env) from eight infected families. Remarkable genetic stability was observed, as only two mutations in LTR (756 bp) and three mutations in env (522 bp) occurred within the 16 vertical transmission chains, including one ambiguous position in each region. The evolutionary rate in HTLV-1 was then calculated using a maximum-likelihood approach that used the highest and lowest possible times of HTLV-1 shared ancestry, given the known transmission histories. The rates for the LTR and env regions were 9.58 x 10-8–1.25 x 10-5 and 7.84x10-7 –2.33x10-5nucleotide substitutions per site per year, respectively. A more precise estimate was obtained for the combined LTR-env data set, which was 7.06x10-7–1.38x10-5substitutions per site per year. We also note an interesting correlation between the occurrence of mutations in HTLV-1 and the age of the individual infected.
Key Words: HTLV-1 • vertical transmission • evolutionary rate • molecular clock
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