Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.     

Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome

Most of the small number of cases of poliomyelitis which occur in countries where Sabin's attenuated poliovirus vaccines are used are temporally associated with administration of vaccine and involve polioviruses of types 2 and 3 (ref. 1). Recent studies have provided convincing evidence that the Sabin type 2 and 3 viruses themselves may revert to a neurovirulent phenotype on passage in man. We report here that a point mutation in the 5' noncoding region of the genome of the poliovirus type 3 vaccine consistently reverts to wild type in strains isolated from cases of vaccine-associated poliomyelitis. Virus with this change is rapidly selected on passage through the human gastrointestinal tract. The change is associated with a demonstrable increase in the neurovirulence of the virus.     

A novel eye in 'eyeless' shrimp from hydrothermal vents of the Mid-Atlantic Ridge

Rimicaris exoculata is a shrimp that swarms over high-temperature (350 degrees C) sulphide chimneys at Mid-Atlantic Ridge hydrothermal fields (3,600 m). This shrimp lacks an externally differentiated eye, having instead a pair of large organs within the cephalothorax immediately beneath the dorsal surface of the transparent carapace, connected by large nerve tracts to the supraesophageal ganglion. These organs contain a visual pigment with an absorption spectrum characteristic of rhodopsin. Ultrastructural evidence for degraded rhabdomeral material suggests the presence of photoreceptors. No image-forming optics are associated with the organs. We interpret these organs as being eyes adapted for detection of low-level illumination and suggest that they evolved in response to a source of radiation associated with the environment of hydrothermal vents.     

Central role of detachment faults in accretion of slow-spreading oceanic lithosphere

The formation of oceanic detachment faults is well established from inactive, corrugated fault planes exposed on sea floor formed along ridges spreading at less than 80 km Myr(-1) (refs 1-4). These faults can accommodate extension for up to 1-3 Myr (ref. 5), and are associated with one of the two contrasting modes of accretion operating along the northern Mid-Atlantic Ridge. The first mode is asymmetrical accretion involving an active detachment fault along one ridge flank. The second mode is the well-known symmetrical accretion, dominated by magmatic processes with subsidiary high-angle faulting and the formation of abyssal hills on both flanks. Here we present an examination of approximately 2,500 km of the Mid-Atlantic Ridge between 12.5 and 35 degrees N, which reveals asymmetrical accretion along almost half of the ridge. Hydrothermal activity identified so far in the study region is closely associated with asymmetrical accretion, which also shows high levels of near-continuous hydroacoustically and teleseismically recorded seismicity. Increased seismicity is probably generated along detachment faults that accommodate a sizeable proportion of the total plate separation. In contrast, symmetrical segments have lower levels of seismicity, which occurs primarily at segment ends. Basalts erupted along asymmetrical segments have compositions that are consistent with crystallization at higher pressures than basalts from symmetrical segments, and with lower extents of partial melting of the mantle. Both seismic evidence and geochemical evidence indicate that the axial lithosphere is thicker and colder at asymmetrical sections of the ridge, either because associated hydrothermal circulation efficiently penetrates to greater depths or because the rising mantle is cooler. We suggest that much of the variability in sea-floor morphology, seismicity and basalt chemistry found along slow-spreading ridges can be thus attributed to the frequent involvement of detachment faults in oceanic lithospheric accretion.     

Widespread active detachment faulting and core complex formation near 13 degrees N on the Mid-Atlantic Ridge

Oceanic core complexes are massifs in which lower-crustal and upper-mantle rocks are exposed at the sea floor. They form at mid-ocean ridges through slip on detachment faults rooted below the spreading axis. To date, most studies of core complexes have been based on isolated inactive massifs that have spread away from ridge axes. Here we present a survey of the Mid-Atlantic Ridge near 13 degrees N containing a segment in which a number of linked detachment faults extend for 75 km along one flank of the spreading axis. The detachment faults are apparently all currently active and at various stages of development. A field of extinct core complexes extends away from the axis for at least 100 km. Our observations reveal the topographic characteristics of actively forming core complexes and their evolution from initiation within the axial valley floor to maturity and eventual inactivity. Within the surrounding region there is a strong correlation between detachment fault morphology at the ridge axis and high rates of hydroacoustically recorded earthquake seismicity. Preliminary examination of seismicity and seafloor morphology farther north along the Mid-Atlantic Ridge suggests that active detachment faulting is occurring in many segments and that detachment faulting is more important in the generation of ocean crust at this slow-spreading ridge than previously suspected.