The DNA sequence and biological annotation of human chromosome 1

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.     

Identification of receptors for neuromedin U and its role in feeding

Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.     

Involuntary orienting to sound improves visual perception

To perceive real-world objects and events, we need to integrate several stimulus features belonging to different sensory modalities. Although the neural mechanisms and behavioural consequences of intersensory integration have been extensively studied, the processes that enable us to pay attention to multimodal objects are still poorly understood. An important question is whether a stimulus in one sensory modality automatically attracts attention to spatially coincident stimuli that appear subsequently in other modalities, thereby enhancing their perceptual salience. The occurrence of an irrelevant sound does facilitate motor responses to a subsequent light appearing nearby. However, because participants in previous studies made speeded responses rather than psychophysical judgements, it remains unclear whether involuntary auditory attention actually affects the perceptibility of visual stimuli as opposed to postperceptual decision and response processes. Here we provide psychophysical evidence that a sudden sound improves the detectability of a subsequent flash appearing at the same location. These data show that the involuntary orienting of attention to sound enhances early perceptual processing of visual stimuli.     

Selection at the Adh locus inDrosophila melanogaster: Adult survivorship-mortality in response to ethanol

Summary Functionally significant biochemical properties of the naturally occurring electrophoretic variants at the Adh locus (ADH^fast and ADH^Slow) are correlated with the adult flies' ability to utilize and survive in an ethanol environment. The results are consistent with the idea that an environmentally dependent form of balancing selection is responsible, at least in part, for the maintenance of the polymorphism at this locus.Acknowledgment. This work was supported by NSF grant DEB 7815466 to J.M.     

Detecting recent positive selection in the human genome from haplotype structure

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.