What's new in PLoS Biology and PLoS Medicine this week? Among else:
The field of behavioral genetics began nearly four decades ago, when Seymour Benzer's laboratory set out to identify circadian rhythm mutants in Drosophila melanogaster. The first of these was called period, and both short and long period alleles were found [1]. It was not until some years later that the mutant gene was identified and exploration of the molecular basis of the circadian clock began in earnest [2,3]. Over the years, forward screens in Drosophila have led to identification of a number of loci that contribute to circadian rhythm function with different phenotypes, including short and long periods and total arrhythmia [4]. Detailed investigations at a genetic and molecular level began to define the cellular and molecular basis of circadian rhythmicity. In its most basic form, the circadian clock of the fruit fly consists of transcriptional activators that turn on expression of two circadian and oscillating genes (period and timeless), which are translated into proteins (PER and TIM) targeted for degradation by phosphorylation. Physical interactions between PER and TIM regulate their movement to the nucleus, where they directly interact with the transcriptional activators and suppress the expression of their own genes [5]. These findings also established the repressor role for PER and TIM in the transcriptional feedback loop. The temporal lag from the transcription of these autorepressors--their translation, nuclear accumulation, and negative feedback until their degradation--requires around 24 hours (circadian), and therefore sets the speed of the clock. An interlocked positive feedback loop has also been characterized. It is remarkable that such a simple, yet elegant model could be the basis of regulation for something as critical as synchronization of behavioral and physiological rhythms to the dramatic changes in light/dark and temperature on planet Earth.
Activating PER Repressor through a DBT-Directed Phosphorylation Switch :
Most proteins involved in circadian transcriptional feedback loops undergo reversible chemical modifications (called phosphorylation) that regulate their activity in a time-of-day-dependent manner. Doubletime (DBT), a Drosophila kinase, phosphorylates the circadian transcriptional repressor PERIOD (PER). Mutations of dbt shorten or lengthen the period of circadian behavioral rhythms, or abolish the rhythms altogether in flies. A mutation of the human ortholog of dbt, casein kinase I (CKI)δ, has been associated with certain forms of a heritable sleep disorder. The disorder may reflect altered activity of a human PER protein, as the syndrome can also be caused by mutation of a CKIÉ/δ phosphorylation site within PER2. In this study, we locate DBT-directed phosphorylation sites in the Drosophila PER protein, including a DBT target region of PER that was previously shown to regulate DBT activity. Two PER domains within this region appear to serve as alternative targets for DBT. Phosphorylation of the upstream domain seems to suppress phosphorylation elsewhere in the region, producing a stable PER protein with little activity as a transcriptional repressor. However, when phosphorylation of the upstream domain is blocked, downstream DBT targets appear to be phosphorylated, producing a highly active, but short-lived repressor. Our results suggest that ordered patterns of DBT-directed phosphorylation contribute to the timing of PER's function and disappearance, and thus influence the pace of the circadian clock.
Going, Going, Gone: Is Animal Migration Disappearing:
Animal migration surely ranks as one of nature's most visible and widespread phenomena. Every minute of every day, somewhere, some place, animals are on the move. The migrants span the animal kingdom, from whales and warblers to dragonflies and salamanders. But is migration an endangered phenomenon? Around the world, many of the most spectacular migrations have either disappeared due to human activities or are in steep decline. Those of us living in eastern North America can no longer experience the flocks of millions of passenger pigeons that temporarily obscured the sun as they migrated to and from their breeding grounds. Nor can residents of the Great Plains climb to the top of a hill and gaze down up hundreds of thousands of bison trekking across the prairies, as was possible less than two centuries ago.
Protecting Migration Corridors: Challenges and Optimism for Mongolian Saiga:
Migrations are an important ecological phenomena rapidly declining throughout the world [1]. Within many ungulate populations, migration is a polymorphic trait; animals can cover either long or short distances, pass across broad swaths of land such as those of caribou (Rangifer tarandus) and wildebeest (Connochaetes taurinus), or squeeze through bottlenecks as narrow as 120 meters as described for pronghorn (Antilocapra americana) [2,3]. Given that the persistence of terrestrial migration is challenged primarily by anthropogenic forces, protection is often possible, assuming the availability of appropriate knowledge concerning movements, threats, and meta-population structure, and the willingness to implement coincident conservation actions that involve local decision makers. Here, we illustrate these issues by profiling an endangered species--the Mongolian saiga (Saiga tatarica mongolica; Figure 1), highlighting the importance of protecting movement routes in light of habitat, human culture, and other sources of population risk.
Beautiful Minds--For How Long:
Over the past few years, the evidence has been building intensively that there is a story to be told about the relationship between cetaceans and primates. More significantly, the nature of this relationship carries implications about more general principles of behavioral evolution and convergence, the process by which similarity between species occurs because of adaptation to similar environments rather than genetic relatedness. Throughout the years, various authors, including myself, have spilled a lot of ink pointing out the striking convergence between cetaceans and primates [1]. At first glance, it might seem that cetaceans and primates evolved in anything but similar environments. However, the concept of an "environment" encompasses the totality of selective pressures on an organism, comprising both the physical setting and the behavioral, ecological, and social milieu. The case of convergence in primates and cetaceans is a compelling example of the primacy of social pressures over physical demands in producing similarities. Now, in Beautiful Minds, Maddalena Bearzi and Craig B. Stanford have written the book that I've been hoping to see for a long time, translating these arguments into an accessible and engaging account for the public [2].
The Soup in My Fly: Evolution, Form and Function of Seminal Fluid Proteins:
The seminal fluid of males from vertebrate and invertebrate taxa is a complex mixture of biologically potent molecules and is far more than a medium to support the successful transit of sperm. But the complexity of this mixture, even in the fly, is only now being fully realised. Recent research is highlighting extraordinarily high evolutionary lability within the genes that encode seminal fluid proteins and is revealing an almost bewildering variety of fitness-related functions. Hence the study of the chemical messages passed from males to females at mating provides a unique window through which to view evolution in action.
Proteomics Reveals Novel Drosophila Seminal Fluid Proteins Transferred at Mating:
Across many species, males transfer both sperm and seminal proteins to their mates. These proteins increase male reproductive success by improving sperm competitive ability and modifying female behavior. In Drosophila, seminal proteins increase female rates of egg-laying and sperm storage and reduce a female's willingness to mate with subsequent suitors. Several male seminal proteins have been extensively characterized, and others have been predicted based on gene expression patterns, yet the full set of proteins that is transferred to females has not been defined. Here we introduce a new proteomic method that identifies transferred seminal proteins in recently mated females and quantifies their relative abundance. We confirm many of the predicted seminal proteins and discover a number of novel seminal fluid components. Some of these proteins show elevated rates of evolution, consistent with their involvement in sexual selection or sexual conflict, and many have arisen by tandem gene duplication. By using this method in three species of Drosophila, we identified lineage-specific components of seminal fluid. Additionally, we developed and validated a method to identify completely new genes in the D. melanogaster genome. These transferred proteins are now targets for follow-up genetic, biochemical, and evolutionary analysis.
Transmitted Minority Drug-Resistant HIV Variants: A New Epidemic?:
Despite high rates of viral turnover and viral evolution, HIV has proven to be surprisingly easy to suppress with combination antiretroviral therapy (ART) in the regions of the world where such treatment is available. Recent reports indicate that the vast majority of patients initiating ART should be able to achieve durable if not indefinite viral suppression [1]. Given that there are now over 20 antiretroviral drugs from six unique classes, even if one regimen fails, others are often readily available. The emerging consensus among clinicians and clinical investigators is that fewer and fewer patients will generate highly resistant HIV during the course of their treatment.
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