Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (ka͞ks) for all 13 mtDNA proteincoding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the ka͞ks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate.

A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences permitted positioning of all nucleotide substitutions according to their order of occurrence. The relative frequency and amino acid conservation of internal branch replacement mutations was found to increase from tropical Africa to temperate Europe and arctic northeastern Siberia. Particularly highly conserved amino acid substitutions were found at the roots of multiple mtDNA lineages from higher latitudes. These same lineages correlate with increased propensity for energy deficiency diseases as well as longevity. Thus, specific mtDNA replacement mutations permitted our ancestors to adapt to more northern climates, and these same variants are influencing our health today.

The MITOMAP () data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of ∼3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster.

High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly during their propagation, provide a probe of Galactic high-energy processes and may enable the observation of phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been measured directly up to approximately 2 teraelectronvolts in previous balloon- or space-borne experiments, and indirectly up to approximately 5 teraelectronvolts using ground-based Cherenkov γ-ray telescope arrays. Evidence for a spectral break in the teraelectronvolt energy range has been provided by indirect measurements, although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range 25 gigaelectronvolts to 4.6 teraelectronvolts by the Dark Matter Particle Explorer (DAMPE) with unprecedentedly high energy resolution and low background. The largest part of the spectrum can be well fitted by a 'smoothly broken power-law' model rather than a single power-law model. The direct detection of a spectral break at about 0.9 teraelectronvolts confirms the evidence found by previous indirect measurements, clarifies the behaviour of the CRE spectrum at energies above 1 teraelectronvolt and sheds light on the physical origin of the sub-teraelectronvolt CREs.

Aerosol samples of PM 2.5 and PM 10 were collected in both summer and winter seasons from 2002 to 2003 synchronously at a traffic site, an industrial site, and a residential site in Beijing, which could basically be the representatives over Beijing. Twenty-three elements and 15 ions together with organic carbon and elemental carbon were analyzed systematically for characterization of Beijing aerosol. PM 2.5 was the major part of the inhalable particles (PM 10 ), as the ratios of PM 2.5 /PM 10 were 0.45-0.48 in summer and 0.52-0.73 in winter. SO 4 2À, NO 3 À , NH 4 + , organic matter, crustal matter, and element carbon were the six dominant species, which totally accounted for 85.8-97.7% of PM 2.5 . Secondary aerosol (SO 4 2À , NO 3 À , and NH 4 + ), road dust or/and long-range transported dust from outside Beijing, industry and motor vehicles emission, coal burning were the major contributors to the air-borne particulate pollution in Beijing. Overall, coal burning and the traffic exhausts, plus the dust from the long-range transport, could be the major sources of the aerosol pollution at Beijing. A relatively even spatial distribution of chemical species in PM 2.5 was found while in PM 10 a significant variation with the highest concentrations at the industrial site in summer and at the residential site in winter was observed. The concentrations of PM 10 , PM 2.5 as well as various chemical species were higher in winter than in summer. The contributions of mineral aerosol from outside Beijing were first estimated with a newly developed element tracer technique, which accounted for 79% and 37% of the total mineral in PM 10 and PM 2.5 in winter, and 19% and 20% in summer, respectively. During the dust storm period from 20 to 22 March, it reached up to 97% in TSP, 79% in PM 10 and 76% in PM 2.5 . This is the technique, firstly, developed for estimating the relative contributions of sources from inside and outside Beijing to the total mineral aerosol and it could provide the basic information in controlling the air-borne particulate pollution at Beijing. r

Mitochondrial bioenergetics plays a key role in multiple basic cellular processes, such as energy production, nucleotide biosynthesis, and iron metabolism. It is an essential system for animals' life and death (apoptosis) and it is required for embryo development. This, in conjunction with its being subjected to adaptive processes in multiple species and its gene products being involved in the formation of reproductive barriers in animals, raises the possibility that mitochondrial bioenergetics could be a candidate genetic mechanism of speciation. Here, we discuss genetic and biochemical evidence for the possible involvement of this unique system, encoded by two genomes (the mitochondrial and nuclear genomes), that differ by an order of magnitude in their mutation rates in processes leading to speciation events.

Common fragile sites are chromosomal loci prone to breakage and rearrangement, hypothesized to provide targets for foreign DNA integration. We cloned a simian virus 40 integration site and showed by f luorescent in situ hybridization analysis that the integration event had occurred within a common aphidicolin-induced fragile site on human chromosome 7, FRA7H. A region of 161 kb spanning FRA7H was defined and sequenced. Several regions with a potential unusual DNA structure, including high-f lexibility, lowstability, and non-B-DNA-forming sequences were identified in this region. We performed a similar analysis on the published FRA3B sequence and the putative partial FRA7G, which also revealed an impressive cluster of regions with high f lexibility and low stability. Thus, these unusual DNA characteristics are possibly intrinsic properties of common fragile sites that may affect their replication and condensation as well as organization, and may lead to fragility.

The DArk Matter Particle Explorer (DAMPE), one of the four scientific space science missions within the framework of the Strategic Pioneer Program on Space Science of the Chinese Academy of Sciences, is a general purpose high energy cosmic-ray and gamma-ray observatory, which was successfully launched on December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE scientific objectives include the study of galactic cosmic rays up to $\sim 10$ TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the search for dark matter signatures in their spectra. In this paper we illustrate the layout of the DAMPE instrument, and discuss the results of beam tests and calibrations performed on ground. Finally we present the expected performance in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart. Phy