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MBE Advance Access published online on January 22, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh053
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted November 4, 2003
© 2004 Society for Molecular Biology and Evolution

Original Articles

The Low Evolutionary Rate of Human T-Cell Lymphotropic Virus Type-1 Confirmed by Analysis of Vertical Transmission Chains

S. Van Dooren 1*, O. G. Pybus 2, M. Salemi 1, H.-F. Liu 3, P. Goubau 4, C. Remondegui 5, A. Talarmin 6, E. Gotuzzo 7, L. C. J. Alcantara 8, B. Galvão-Castro 8, and Anne-Mieke Vandamme 1

1 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
2 Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK
3 Department. of Medical Research, Mackay Memorial Hospital, Min-Sheng Road 45, Taipei- Tamshui 251, Taiwan
4 Université Catholique de Louvain, Unité de Virologie, 1200 Bruxelles, Belgium
5 Hospital San Roque, San Salvador de Jujuy, Argentina
6 Laboratoire de Rétrovirologie, Institut Pasteur de la Guyane, BP6010, 23 Av. Pasteur, 97300 Cayenne, French Guiana
7 Instituto de Medicina Tropical 'Alexander Von Humboldt', Universidad Peruana Cayetano Heredia, Lima, Peru
8 Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Bahia School of Medicine and Public Health, Salvador, Bahia, Brazil

* To whom correspondence should be addressed. E-mail: Sonia.VanDooren{at}uz.kuleuven.ac.be.


  Abstract

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 analysed two variable regions of the HTLV-1 genome (LTR and env) from 8 infected families. Remarkable genetic stability was observed, as only 2 mutations in LTR (756bp) and 3 mutations in env (522bp) 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*10-8-1.25*10-5 and 7.84*10-7-2.33*10-5 nucleotide substitutions per site per year, respectively. A more precise estimate was obtained for the combined LTR-env data set, which was 7.06*10-7-1.38*10-5 substitutions 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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