The cost of inbreeding in Arabidopsis

Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) with fixed differences between species (divergence). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the time since species divergence allows combination of data across genes. In a comparison of amino-acid replacements among species of the mustard weed Arabidopsis with those among species of the fruitfly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory that species with a high frequency of inbreeding are less efficient in eliminating deleterious mutations owing to their reduced effective population size.     

Regulatory evolution across the protein interaction network

Protein-protein interactions may impose constraints on both structural and regulatory evolution. Here we show that protein-protein interactions are negatively associated with evolutionary variation in gene expression. Moreover, interacting proteins have similar levels of variation in expression, and their expression levels are positively correlated across strains. Our results suggest that interacting proteins undergo similar evolutionary dynamics, and that their expression levels are evolutionarily coupled. These patterns hold for organisms as diverse as budding yeast and fruit flies.     

Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria

A nuclear encoded mitochondrial heat-shock protein hsp60 is required for the assembly into oligomeric complexes of proteins imported into the mitochondrial matrix. hsp60 is a member of the 'chaperonin' class of protein factors, which include the Escherichia coli groEL protein and the Rubisco subunit-binding protein of chloroplasts.     

Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding.

The main stress proteins of Escherichia coli function in an ordered protein-folding reaction. DnaK (heat-shock protein 70) recognizes the folding polypeptide as an extended chain and cooperates with DnaJ in stabilizing an intermediate conformational state lacking ordered tertiary structure. Dependent on GrpE and ATP hydrolysis, the protein is then transferred to GroEL (heat-shock protein 60) which acts catalytically in the production of the native state. This sequential mechanism of chaperone action may represent an important pathway for the folding of newly synthesized polypeptides.     

Direct frequency comb spectroscopy in the extreme ultraviolet

The development of the optical frequency comb (a spectrum consisting of a series of evenly spaced lines) has revolutionized metrology and precision spectroscopy owing to its ability to provide a precise and direct link between microwave and optical frequencies. A further advance in frequency comb technology is the generation of frequency combs in the extreme-ultraviolet spectral range by means of high-harmonic generation in a femtosecond enhancement cavity. Until now, combs produced by this method have lacked sufficient power for applications, a drawback that has also hampered efforts to observe phase coherence of the high-repetition-rate pulse train produced by high-harmonic generation, which is an extremely nonlinear process. Here we report the generation of extreme-ultraviolet frequency combs, reaching wavelengths of 40?nanometres, by coupling a high-power near-infrared frequency comb to a robust femtosecond enhancement cavity. These combs are powerful enough for us to observe single-photon spectroscopy signals for both an argon transition at 82?nanometres and a neon transition at 63?nanometres, thus confirming the combs' coherence in the extreme ultraviolet. The absolute frequency of the argon transition has been determined by direct frequency comb spectroscopy. The resolved ten-megahertz linewidth of the transition, which is limited by the temperature of the argon atoms, is unprecedented in this spectral region and places a stringent upper limit on the linewidth of individual comb teeth. Owing to the lack of continuous-wave lasers, extreme-ultraviolet frequency combs are at present the only promising route to extending ultrahigh-precision spectroscopy to the spectral region below 100?nanometres. At such wavelengths there is a wide range of applications, including the spectroscopy of electronic transitions in molecules, experimental tests of bound-state and many-body quantum electrodynamics in singly ionized helium and neutral helium, the development of next-generation 'nuclear' clocks and searches for variation of fundamental constants using the enhanced sensitivity of highly charged ions.     

Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis

Mitochondrial heat-shock protein hsp60 functions in the folding of proteins imported into mitochondria. Folding occurs at the surface of hsp60 in an ATP-mediated reaction, followed by release of the bound polypeptides. We propose that hsp60 catalyses protein folding.     

Molecular chaperones in protein folding and proteostasis

Most proteins must fold into defined three-dimensional structures to gain functional activity. But in the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding. Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis (proteostasis). Recent advances suggest that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. Interventions in these and numerous other pathological states may spring from a detailed understanding of the pathways underlying proteome maintenance.     

A genome-wide map of diversity in Plasmodium falciparum

Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite.