Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.
Fitness epistasis, the interaction among alleles at different loci in their effects on fitness, has potentially important consequences for adaptive evolution. We investigated fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein (gp120). Seven mutations putatively involved in the adaptation of the second conserved to third variable protein region (C2-V3) to the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry were engineered singly and in combinations on the wild-type genetic background and their effects on viral infectivity were measured. Epistasis was found to be common and complex, involving not only pairwise interactions, but also higher-order interactions. Interactions could also be surprisingly strong, changing fitness by more than 9 orders of magnitude, which is explained by some single mutations being practically lethal. A consequence of the observed epistasis is that many of the minimum-length mutational trajectories between the wild type and the mutant with highest fitness on cells expressing the alternative coreceptor are selectively inaccessible. These results may help explain the difficulty of evolving viruses that use the alternative coreceptor in culture and the delayed evolution of this phenotype in natural infection. Knowledge of common, complex, and strong fitness interactions among amino acids is necessary for a full understanding of protein evolution.
Since European badgers (Meles meles L.) form non-cooperative groups in parts of their geographic range, but are solitary elsewhere, their social systems have been at the centre of a debate about the evolution of group living in the Carnivora. In a recent review of models of non-cooperative sociality, Woodroffe and Macdonald (1993) presented evidence in favour of two hypotheses, which suggested that badger groups might form because either the distribution of blocks of foodrich habitat, or the economics of excavating new setts, prevented the division of group territories into individual territories. We present data upon the response of badger spatial organisation to a reduction in food-patch dispersion, brought about by the conversion of carthwormpoor arable land to earthworm-rich pasture over a 15-year period. This change in the distribution of earthworm-rich habitats was accompanied by territory fission, facilitated by the excavation of new setts. This indicates that the availability of sett sites had not constrained territory size at the start of the study. However, sett distribution did define the size and configuration of the daughter territories. We also show that variation among territories in the availability of food-rich habitats was reflected in the reproductive rates and body weights of the groups that inhabited them, although there was no detectable effect upon group size.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.