Gradual degradation seems inevitable for non‐recombining sex chromosomes. This has been supported by the observation of degenerated non‐recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ∼5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal repair through (...) gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex‐determining chromosomes by studying simpler sex‐determining chromosomal regions of unicellular and multicellular microorganisms. (shrink)

Calcineurin is a Ca2+/calmodulin‐activated protein phosphatase that is conserved in eukaryotes, from yeast to humans, and is the conserved target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast and fungi established the molecular basis of calcineurin inhibition by the cyclophilin A–CsA and FKBP12–FK506 complexes. Calcineurin also functions in fungi to control a myriad of physiological processes including cell cycle progression, cation homeostasis, and morphogenesis. Recent investigations into the molecular mechanisms of pathogenesis in Candida albicans and (...) Cryptococcus neoformans, two fungi that cause life‐threatening infections in humans, have revealed an essential role for calcineurin in morphogenesis, virulence, and antifungal drug action. Novel non‐immunosuppressive analogs of the calcineurin inhibitors CsA and FK506 that retain antifungal activity have been identified and hold promise as candidate antifungal drugs. In addition, comparisons of calcineurin function in both fungi and humans may identify fungal‐specific components of calcineurin‐signaling pathways that could be targeted for therapy, as well as conserved elements of calcium signaling events. BioEssays 24:894–903, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

One popular recombinant DNA tool is the EcoRI endonuclease, which cleaves DNA at GAATTC sites and serves as a paradigm for sequence specific DNA‐enzyme interactions. The recently revised X‐ray crystal structure of an EcoRI‐DNA complex reveals EcoRI employs novel DNA recognition motifs, a four α‐helix bundle and two extended chains, which project into the major groove to contact substrate purines and pyrimidines. Interestingly, pyrimidine contacts had been predicted based on genetic and biochemical studies. Current work focuses on the EcoRI active (...) site structure, enzyme and substrate conformational changes during catalysis, and host‐restriction system interactions. (shrink)