New and Exciting in PLoS ONE

There are 31 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week - you go and look for your own favourites:

High-Pitched Notes during Vocal Contests Signal Genetic Diversity in Ocellated Antbirds:

Animals use honest signals to assess the quality of competitors during aggressive interactions. Current theory predicts that honest signals should be costly to produce and thus reveal some aspects of the phenotypic or genetic quality of the sender. In songbirds, research indicates that biomechanical constraints make the production of some acoustic features costly. Furthermore, recent studies have found that vocal features are related to genetic diversity. We linked these two lines of research by evaluating if constrained acoustic features reveal male genetic diversity during aggressive interactions in ocellated antbirds (Phaenostictus mcleannani). We recorded the aggressive vocalizations of radiotagged males at La Selva Biological Station in Costa Rica, and found significant variation in the highest frequency produced among individuals. Moreover, we detected a negative relationship between the frequency of the highest pitched note and vocalization duration, suggesting that high pitched notes might constrain the duration of vocalizations through biomechanical and/or energetic limitations. When we experimentally exposed wild radiotagged males to simulated acoustic challenges, the birds increased the pitch of their vocalization. We also found that individuals with higher genetic diversity (as measured by zygosity across 9 microsatellite loci) produced notes of higher pitch during aggressive interactions. Overall, our results suggest that the ability to produce high pitched notes is an honest indicator of male genetic diversity in male-male aggressive interactions.

Associative Learning during Early Adulthood Enhances Later Memory Retention in Honeybees:

Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i) a rewarded experience through the offering of scented food, or (ii) a non-rewarded experience with a pure volatile compound in the rearing environment. Early rewarded experiences (either at 1-4 or 5-8 days of adult age) enhanced retention performance in 9-12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5-8 days of adult age. Associative memories acquired at 9-12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees.

How Many Genetic Variants Remain to Be Discovered?:

A great majority of genetic markers discovered in recent genome-wide association studies have small effect sizes, and they explain only a small fraction of the genetic contribution to the diseases. How many more variants can we expect to discover and what study sizes are needed? We derive the connection between the cumulative risk of the SNP variants to the latent genetic risk model and heritability of the disease. We determine the sample size required for case-control studies in order to achieve a certain expected number of discoveries in a collection of most significant SNPs. Assuming similar allele frequencies and effect sizes of the currently validated SNPs, complex phenotypes such as type-2 diabetes would need approximately 800 variants to explain its 40% heritability. Much smaller numbers of variants are needed if we assume rare-variants but higher penetrance models. We estimate that up to 50,000 cases and an equal number of controls are needed to discover 800 common low-penetrant variants among the top 5000 SNPs. Under common and rare low-penetrance models, the very large studies required to discover the numerous variants are probably at the limit of practical feasibility. Under rare-variant with medium- to high-penetrance models (odds-ratios between 1.6 and 4.0), studies comparable in size to many existing studies are adequate provided the genotyping technology can interrogate more and rarer variants.

Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies:

Studies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics). We conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research. Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. Study characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study. From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25:1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40-222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p<0.05) reported associations suggesting the possibility of significance-chasing bias. Despite 136 examples of gene/drug interventions being the subject of â¥4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points. The high expectation but limited translation of pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines.