11 research outputs found
Rapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations
The genes of the major histocompatibility complex are the most polymorphic genes in vertebrates, with more than 1,000 alleles described in human populations. How this polymorphism is maintained, however, remains an evolutionary puzzle. Major histocompatibility complex genes have a crucial function in the adaptive immune system by presenting parasite-derived antigens to T lymphocytes. Because of this function, varying parasite-mediated selection has been proposed as a major evolutionary force for maintaining major histocompatibility complex polymorphism. A necessary prerequisite of such a balancing selection process is rapid major histocompatibility complex allele frequency shifts resulting from emerging selection by a specific parasite. Here we show in six experimental populations of sticklebacks, each exposed to one of two different parasites, that only those major histocompatibility complex alleles providing resistance to the respective specific parasite increased in frequency in the next host generation. This result demonstrates experimentally that varying parasite selection causes rapid adaptive evolutionary changes, thus facilitating the maintenance of major histocompatibility complex polymorphism
Standing genetic variation and the evolution of drug resistance in HIV
Drug resistance remains a major problem for the treatment of HIV. Resistance
can occur due to mutations that were present before treatment starts or due to
mutations that occur during treatment. The relative importance of these two
sources is unknown. We study three different situations in which HIV drug
resistance may evolve: starting triple-drug therapy, treatment with a single
dose of nevirapine and interruption of treatment. For each of these three cases
good data are available from literature, which allows us to estimate the
probability that resistance evolves from standing genetic variation. Depending
on the treatment we find probabilities of the evolution of drug resistance due
to standing genetic variation between 0 and 39%. For patients who start
triple-drug combination therapy, we find that drug resistance evolves from
standing genetic variation in approximately 6% of the patients. We use a
population-dynamic and population-genetic model to understand the observations
and to estimate important evolutionary parameters. We find that both, the
effective population size of the virus before treatment, and the fitness of the
resistant mutant during treatment, are key-parameters that determine the
probability that resistance evolves from standing genetic variation.
Importantly, clinical data indicate that both of these parameters can be
manipulated by the kind of treatment that is used.Comment: 33 pages 6 figure