The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.     

The bonobo genome compared with the chimpanzee and human genomes

Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.     

Rapid evolutionary innovation during an Archaean genetic expansion

The natural history of Precambrian life is still unknown because of the rarity of microbial fossils and biomarkers. However, the composition of modern-day genomes may bear imprints of ancient biogeochemical events. Here we use an explicit model of macroevolution including gene birth, transfer, duplication and loss events to map the evolutionary history of 3,983 gene families across the three domains of life onto a geological timeline. Surprisingly, we find that a brief period of genetic innovation during the Archaean eon, which coincides with a rapid diversification of bacterial lineages, gave rise to 27% of major modern gene families. A functional analysis of genes born during this Archaean expansion reveals that they are likely to be involved in electron-transport and respiratory pathways. Genes arising after this expansion show increasing use of molecular oxygen (P = 3.4 × 10(-8)) and redox-sensitive transition metals and compounds, which is consistent with an increasingly oxygenating biosphere.     

A luminous quasar at a redshift of z = 7.085

The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS?J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS?J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS?J1120+0641 is 1.9?megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS?J1120+0641 exceeded 0.1.     

Chironomidae (Diptera) of the Colorado River, Grand Canyon, Arizona, USA, II: factors influencing distribution

Biogeographic, flow regulation (water clarity and temperature), and temporal influences affect the composition of the chironomid midge assemblage in the Colorado River between Glen Canyon Dam and Lake Mead. This assemblage is dominated by euryecious Nearctic and Holarctic orthocladine taxa (23 of 38 total species, total weighted relative abundance [WRA] = 0.972) and includes a minor Neotropical component. Chironomid species richness increases over distance downstream from the dam, and dominance shifts across 3 turbidity segments. Eleven species occur in the cold-stenothermic Clearwater (CW) segment between the dam and the 1st perennial tributary (the Paria River, 26 km from the dam). Chironomid diversity increases from 18 to 24 species in the variably turbid (VT) and usually turbid (UT) segments downstream, respectively. Total Cricotopus spp. WRA is negatively correlated with distance (turbidity), white total Chironominae WRA shows the opposite pattern. In contrast to chironomid diversity, species density decreases from 0.42 species/km in the CW segment to 0.19 and 0.08 species/km in the VT and UT segments, respectively. Seasonal dominance shifts slightly from orthocladine Eukiefferiella spp. in winter (WRA = 0.101) to Cricotopus spp. (WRA = 0.165) in summer. Total WRA is lowest in spring (0.191). The assemblage is depauperate compared with other western rivers and has changed over post-dam time.     

Regional econometric income forecast accuracy

Econometric prediction accuracy for personal income forecasts is examined for a region of the United States. Previously published regional structural equation model (RSEM) forecasts exist ex ante for the state of New Mexico and its three largest metropolitan statistical areas: Albuquerque, Las Cruces and Santa Fe. Quarterly data between 1983 and 2000 are utilized at the state level. For Albuquerque, annual data from 1983 through 1999 are used. For Las Cruces and Santa Fe, annual data from 1990 through 1999 are employed. Univariate time series, vector autoregressions and random walks are used as the comparison criteria against structural equation simulations. Results indicate that ex ante RSEM forecasts achieved higher accuracy than those simulations associated with univariate ARIMA and random walk benchmarks for the state of New Mexico. The track records of the structural econometric models for Albuquerque, Las Cruces and Santa Fe are less impressive. In some cases, VAR benchmarks prove more reliable than RSEM income forecasts. In other cases, the RSEM forecasts are less accurate than random walk alternatives. Copyright © 2005 John Wiley & Sons, Ltd.     

Familial dementia caused by polymerization of mutant neuroserpin.

Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases.