Evolution of human immunodeficiency virus under selection and weak recombination.
نویسندگان
چکیده
To predict emergence of drug resistance in patients undergoing antiretroviral therapy, we study accumulation of preexisting beneficial alleles in a haploid population of N genomes. The factors included in the model are selection with the coefficient s and recombination with the small rate per genome r (r << s sqrt of k, where k is the average number of less-fit loci per genome). Mutation events are neglected. To describe evolution at a large number of linked loci, we generalize the analytic method we developed recently for an asexual population. We show that the distribution of genomes over the deleterious allele number moves in time as a "solitary wave" that is quasi-deterministic in the middle (on the average) but has stochastic edges. We arrive at a single-locus expression for the average accumulation rate, in which the effects of linkage, recombination, and random drift are all accounted for by the effective selection coefficient s lnNr/lnNs(2)k/r. At large N, the effective selection coefficient approaches the single-locus value s. Below the critical size N(c) approximately 1/r, a population eventually becomes a clone, recombination cannot produce new sequences, and virus evolution stops. Taking into account finite mutation rate predicts a small, finite rate of evolution at N < N(c). We verify the accuracy of the results analytically and by Monte Carlo simulation. On the basis of our findings, we predict that partial depletion of the HIV population by combined anti-retroviral therapy can suppress emergence of drug-resistant strains.
منابع مشابه
Cytomegalovirus Active Infection in Persons Infected with Human Immunodeficiency Virus
Background and Objective: Cytomegalovirus (CMV), one of the most common opportunistic pathogens in patients infected with human immunodeficiency virus (HIV), can cause the diseases such as encephalitis, pneumonia, and chorioretinitis. This study aimed at molecular studying of CMV infection in individuals infected with the human immunodeficiency virus. Material and Methods: In this study, 50 ven...
متن کاملPhylogenetic evidence for frequent positive selection and recombination in the meningococcal surface antigen PorB.
Previous estimates of rates of synonymous (d(S)) and nonsynonymous (d(N)) substitution among Neisseria meningitidis gene sequences suggested that the surface loops of the variable outer membrane protein PorB were under only weak selection pressure from the host immune response. These findings were consistent with studies indicating that PorB variants were not always protective in immunological ...
متن کاملA genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination.
It has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contr...
متن کاملQuantification Analysis of Dot Blot Assays for Human Immunodeficiency Virus Type 1 and 2 Antibodies
Objective Dot Blot (DB) assay provides highly specific results, but usually not reliable for quantification of antibody production. The need for a more objective DB assay to provide a better definition of the immune status, against HIV antigens, promoted this study to be done to develop a quantitative DB assay. Material and Methods Dot blot (DB) strips for antibodies directed to human immuno...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Genetics
دوره 170 1 شماره
صفحات -
تاریخ انتشار 2005