An index to assess the health and benefits of the global ocean

The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled human–ocean systems. We created an index comprising ten diverse public goals for a healthy coupled human–ocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 36–86), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.     

Visualizing molecular juggling within a B12-dependent methyltransferase complex

Derivatives of vitamin B(12) are used in methyl group transfer in biological processes as diverse as methionine synthesis in humans and CO(2) fixation in acetogenic bacteria. This seemingly straightforward reaction requires large, multimodular enzyme complexes that adopt multiple conformations to alternately activate, protect and perform catalysis on the reactive B(12) cofactor. Crystal structures determined thus far have provided structural information for only fragments of these complexes, inspiring speculation about the overall protein assembly and conformational movements inherent to activity. Here we present X-ray crystal structures of a complete 220?kDa complex that contains all enzymes responsible for B(12)-dependent methyl transfer, namely the corrinoid iron-sulphur protein and its methyltransferase from the model acetogen Moorella thermoacetica. These structures provide the first three-dimensional depiction of all protein modules required for the activation, protection and catalytic steps of B(12)-dependent methyl transfer. In addition, the structures capture B(12) at multiple locations between its 'resting' and catalytic positions, allowing visualization of the dramatic protein rearrangements that enable methyl transfer and identification of the trajectory for B(12) movement within the large enzyme scaffold. The structures are also presented alongside in crystallo spectroscopic data, which confirm enzymatic activity within crystals and demonstrate the largest known conformational movements of proteins in a crystalline state. Taken together, this work provides a model for the molecular juggling that accompanies turnover and helps explain why such an elaborate protein framework is required for such a simple, yet biologically essential reaction.     

Germline epimutation of MLH1 in individuals with multiple cancers

Epigenetic silencing can mimic genetic mutation by abolishing expression of a gene. We hypothesized that an epimutation could occur in any gene as a germline event that predisposes to disease and looked for examples in tumor suppressor genes in individuals with cancer. Here we report two individuals with soma-wide, allele-specific and mosaic hypermethylation of the DNA mismatch repair gene MLH1. Both individuals lack evidence of genetic mutation in any mismatch repair gene but have had multiple primary tumors that show mismatch repair deficiency, and both meet clinical criteria for hereditary nonpolyposis colorectal cancer. The epimutation was also present in spermatozoa of one of the individuals, indicating a germline defect and the potential for transmission to offspring. Germline epimutation provides a mechanism for phenocopying of genetic disease. The mosaicism and nonmendelian inheritance that are characteristic of epigenetic states could produce patterns of disease risk that resemble those of polygenic or complex traits.     

The worldwide leaf economics spectrum

Bringing together leaf trait data spanning 2,548 species and 175 sites we describe, for the first time at global scale, a universal spectrum of leaf economics consisting of key chemical, structural and physiological properties. The spectrum runs from quick to slow return on investments of nutrients and dry mass in leaves, and operates largely independently of growth form, plant functional type or biome. Categories along the spectrum would, in general, describe leaf economic variation at the global scale better than plant functional types, because functional types overlap substantially in their leaf traits. Overall, modulation of leaf traits and trait relationships by climate is surprisingly modest, although some striking and significant patterns can be seen. Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.     

DNA sequence and analysis of human chromosome 18

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.     

The pelvic fin and girdle of Panderichthys and the origin of tetrapod locomotion

One of the most marked transformations in the vertebrate transition to land was that of fins to limbs. This transformation involved not only the generation of morphological novelties (digits, sacrum) but also a shift in locomotory dominance from the pectoral to the pelvic appendage. Despite its importance, the transformation from pelvic fin to hindlimb is the least studied and least well-documented part of this transformation, which is bracketed by the osteolepiform Eusthenopteron and the early tetrapods Ichthyostega and Acanthostega, but is not directly illuminated by any intermediate form. Panderichthys is the closest tetrapod relative currently represented by complete fossils, but its pelvic fin skeleton has not been described. Here, I present the only known articulated pelvic fin endoskeleton and associated partial pelvis of Panderichthys. The pelvic girdle is even less tetrapod-like than that of the osteolepiform Eusthenopteron, but the pelvic fin endoskeleton shares derived characteristics with basal tetrapods despite being more primitive than the pectoral fin of Panderichthys. The evolution of tetrapod locomotion appears to have passed through a stage of body-flexion propulsion, in which the pelvic fins played a relatively minor anchoring part, before the emergence of hindlimb-powered propulsion in the interval between Panderichthys and Acanthostega.     

A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig

Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation.