Divergence of Peroxisome Membrane Gene Sequence and Expression Between Yeast Species.

Large population-genomic sequencing studies can enable highly-powered analyses of sequence signatures of natural selection. Genome repositories now available for yeast make it a premier model for studies of the molecular mechanisms of adaptation. We mined the genomes of hundreds of isolates of the sister species and to identify sequence hallmarks of adaptive divergence between the two.

Identification of HIV-1 Envelope Mutations that Enhance Entry Using Macaque CD4 and CCR5.

Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env's gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses.

Genetic dissection of interspecific differences in yeast thermotolerance.

Some of the most unique and compelling survival strategies in the natural world are fixed in isolated species. To date, molecular insight into these ancient adaptations has been limited, as classic experimental genetics has focused on interfertile individuals in populations. Here we use a new mapping approach, which screens mutants in a sterile interspecific hybrid, to identify eight housekeeping genes that underlie the growth advantage of Saccharomyces cerevisiae over its distant relative Saccharomyces paradoxus at high temperature.

Polygenic evolution of a sugar specialization trade-off in yeast.

The evolution of novel traits can involve many mutations scattered throughout the genome. Detecting and validating such a suite of alleles, particularly if they arose long ago, remains a key challenge in evolutionary genetics. Here we dissect an evolutionary trade-off of unprecedented genetic complexity between long-diverged species.

Rare variants in hypermutable genes underlie common morphology and growth traits in wild Saccharomyces paradoxus.

Understanding the molecular basis of common traits is a primary challenge of modern genetics. One model holds that rare mutations in many genetic backgrounds may often phenocopy one another, together explaining the prevalence of the resulting trait in the population. For the vast majority of phenotypes, the role of rare variants and the evolutionary forces that underlie them are unknown.

Evolution of a membrane protein regulon in Saccharomyces.

Expression variation is widespread between species. The ability to distinguish regulatory change driven by natural selection from the consequences of neutral drift remains a major challenge in comparative genomics. In this work, we used observations of mRNA expression and promoter sequence to analyze signatures of selection on groups of functionally related genes in Saccharomycete yeasts.

CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy.

Introduction: CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course.

Materials And Methods: In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment.