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Bette Korber, James Theiler, Steven Wolinsky*
The evolutionary history of human immunodeficiency virus (HIV) is unfolding even as we study it, a consequence of the underlying genetic variation by mutation (1), recombination (2, 3), and frequent insertions and deletions (4). Studies of the evolutionary history of HIV enable us to extrapolate into the past and make estimates of the age of the epidemic, as well as make predictions of the potential for variation in the future that will affect vaccine development.
The HIV-1 main (M) group, although dominant in the global acquired immunodeficiency syndrome (AIDS) epidemic, is but one cluster in a complex array of simian and human lentiviruses (5). Other lentiviruses that can cause AIDS in humans include HIV-2, a distant cousin of HIV-1 that is common in West Africa and in India (6) and appears to have entered the human population through multiple zoonotic infections from simian immunodeficiency virus (SIV)-infected sooty mangabeys (5), and HIV-1 group O (7), a very distinctive "outlier" form of HIV-1 that is genetically more distant from the HIV-1 M group than a virus obtained from a chimpanzee caught in the wild in Gabon (CPZGAB) (5, 8). Nonetheless, it is the M group that has been preferentially amplified in the human population during the course of human events; whether this was due to chance or to biological differences in human lentiviruses remains unclear.
Differences can be found in greater than 25% of positions in envelope nucleotide sequences of diverse isolates within the M group. Genetic distance is represented in a phylogenetic tree as a branch length and is an estimate of how many mutational events actually occurred between two sequences. A simple tally of the number of changes between two sequences will underestimate the true genetic distance, because multiple mutational events may have occurred at any given site since divergence from a common ancestor. Phylogenetic methods use different ways to estimate the genetic distance between sequences and to organize a set of sequences into a hierarchy of ever more distantly related sequences (9). There are clearly defined associations among HIV-1 M group viruses that become apparent through phylogenetic analysis. This has led to the development of an alphabetical subtype taxonomy (10, II) (Fig. 1), with designations A to...