The genome of the simian and human malaria parasite Plasmodium knowlesi

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.     

Drought sensitivity shapes species distribution patterns in tropical forests

Although patterns of tree species distributions along environmental gradients have been amply documented in tropical forests, mechanisms causing these patterns are seldom known. Efforts to evaluate proposed mechanisms have been hampered by a lack of comparative data on species' reactions to relevant axes of environmental variation. Here we show that differential drought sensitivity shapes plant distributions in tropical forests at both regional and local scales. Our analyses are based on experimental field assessments of drought sensitivity of 48 species of trees and shrubs, and on their local and regional distributions within a network of 122 inventory sites spanning a rainfall gradient across the Isthmus of Panama. Our results suggest that niche differentiation with respect to soil water availability is a direct determinant of both local- and regional-scale distributions of tropical trees. Changes in soil moisture availability caused by global climate change and forest fragmentation are therefore likely to alter tropical species distributions, community composition and diversity.     

Boron and oxygen isotope evidence for recycling of subducted components over the past 2.5 Gyr

Evidence for the deep recycling of surficial materials through the Earth's mantle and their antiquity has long been sought to understand the role of subducting plates and plumes in mantle convection. Radiogenic isotope evidence for such recycling remains equivocal because the age and location of parent-daughter fractionation are not known. Conversely, while stable isotopes can provide irrefutable evidence for low-temperature fractionation, their range in most unaltered oceanic basalts is limited and the age of any variation is unconstrained. Here we show that delta(18)O ratios in basalts from the Azores are often lower than in pristine mantle. This, combined with increased Nb/B ratios and a large range in delta(11)B ratios, provides compelling evidence for the recycling of materials that had undergone fractionation near the Earth's surface. Moreover, delta(11)B is negatively correlated with (187)Os/(188)Os ratios, which extend to subchondritic values, constraining the age of the high Nb/B, (11)B-enriched endmember to be more than 2.5 billion years (Gyr) old. We infer this component to be melt- and fluid-depleted lithospheric mantle from a subducted oceanic plate, whereas other Azores basalts contain a contribution from approximately 3-Gyr-old melt-enriched basalt. We conclude that both components are most probably derived from an Archaean oceanic plate that was subducted, arguably into the deep mantle, where it was stored until thermal buoyancy caused it to rise beneath the Azores islands approximately 3 Gyr later.     

De novo assembly and genotyping of variants using colored de Bruijn graphs

Detecting genetic variants that are highly divergent from a reference sequence remains a major challenge in genome sequencing. We introduce de novo assembly algorithms using colored de Bruijn graphs for detecting and genotyping simple and complex genetic variants in an individual or population. We provide an efficient software implementation, Cortex, the first de novo assembler capable of assembling multiple eukaryotic genomes simultaneously. Four applications of Cortex are presented. First, we detect and validate both simple and complex structural variations in a high-coverage human genome. Second, we identify more than 3 Mb of sequence absent from the human reference genome, in pooled low-coverage population sequence data from the 1000 Genomes Project. Third, we show how population information from ten chimpanzees enables accurate variant calls without a reference sequence. Last, we estimate classical human leukocyte antigen (HLA) genotypes at HLA-B, the most variable gene in the human genome.     

X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment

Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females. Aided by systematic resequencing of 737 X chromosome genes, we identified different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR. Five mutations resulted in the introduction of a premature termination codon. Study of two of these demonstrated nonsense-mediated decay of PCDH19 mRNA. The two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation.