Information Technology Reference
In-Depth Information
1.0
0.8
0.6
0.25
0.50
1.00
0.4
0.2
0.0
0
20
40
60
80
100
120
Generation
Fig. 2.
The change in viral population mean fitness over viral generations in the absence of
antibody selection. Populations were initialized with a suboptimal R5 V3 sequence. Plots for
different selection coefficient scaling constants (strengths of coreceptor selection) are shown.
Lines are means of 20 replicate simulations. The following parameter values were used: 10
5
cells, 3 x 10
5
virions, 10
-5
mutation per nucleotide per cycle, 10
-3
crossover per nucleotide per
cycle, 100 virions budded per cell, and 0.03 probability of viral genome integration.
Simulations were also run with populations initialized with optimal, or near-
optimal, R5, X4R5, or X4 V3 sequences (Fig. 4). The optimal R5 V3 sequence has a
fitness of one in the absence of antibody selection and does not change over the
several hundred generations simulated. The X4R5 V3 sequence is near-optimal in
the sense that it contains the most common amino acid for its phenotype at all sites
but one; this was the sequence in the Swiss-Prot protein database most similar to the
optimal sequence. The relative fitness of this near-optimal X4R5 sequence is 0.37
because of the difference from the optimal sequence and because it violates several
amino acid covariation patterns (See 9.3.1.1). Selection of covarying amino acids
appears to have changed the sequence phenotype to R5, followed by evolution to the
optimal R5 V3 sequence. The optimal X4 sequence also has a fitness of less than one
because it violates several amino acid covariation patterns. However, selection of
covarying amino acids, which increased population mean fitness, did not change the
phenotype. X4 sequences attained a mean fitness of only 0.64 after 500 generations
of selection.
