In the last 40 years, the Asian tiger mosquito Aedes albopictus, indigenous to East Asia, has colonized every continent except Antarctica. Its spread is a major public health concern, given that this species is a competent vector for numerous arboviruses, including those causing dengue, chikungunya, West Nile, and the recently emerged Zika fever. To acquire more information on the ancestral source(s) of adventive populations and the overall diffusion process from its native range, we analyzed the mitogenome variation of 27 individuals from representative populations of Asia, the Americas, and Europe. Phylogenetic analyses revealed five haplogroups in Asia, but population surveys appear to indicate that only three of these (A1a1, A1a2, and A1b) were involved in the recent worldwide spread. We also found out that a derived lineage (A1a1a1) within A1a1, which is now common in Italy, most likely arose in North America from an ancestral Japanese source. These different genetic sources now coexist in many of the recently colonized areas, thus probably creating novel genomic combinations which might be one of the causes of the apparently growing ability of A. albopictus to expand its geographical range.

Sardinians are “outliers” in the European genetic landscape and, according to paleogenomic nuclear data, the closest to early European Neolithic farmers. To learn more about their genetic ancestry, we analyzed 3,491 modern and 21 ancient mitogenomes from Sardinia. We observed that 78.4% of modern mitogenomes cluster into 89 haplogroups that most likely arose in situ. For each Sardinian-specific haplogroup (SSH), we also identified the upstream node in the phylogeny, from which non-Sardinian mitogenomes radiate. This provided minimum and maximum time estimates for the presence of each SSH on the island. In agreement with demographic evidence, almost all SSHs coalesce in the post-Nuragic, Nuragic and Neolithic-Copper Age periods. For some rare SSHs, however, we could not dismiss the possibility that they might have been on the island prior to the Neolithic, a scenario that would be in agreement with archeological evidence of a Mesolithic occupation of Sardinia.

Recent and compelling archaeological evidence attests to human presence ∼14.5 ka at multiple sites in South America and a very early exploitation of extreme high-altitude Andean environments. Considering that, according to genetic evidence, human entry into North America from Beringia most likely occurred ∼16 ka, these archeological findings would imply an extremely rapid spread along the double continent. To shed light on this issue from a genetic perspective, we first completely sequenced 217 novel modern mitogenomes of Native American ancestry from the northwestern area of South America (Ecuador and Peru); we then evaluated them phylogenetically together with other available mitogenomes (430 samples, both modern and ancient) from the same geographic area and, finally, with all closely related mitogenomes from the entire double continent. We detected a large number (N = 48) of novel subhaplogroups, often branching into further subclades, belonging to two classes: those that arose in South America early after its peopling and those that instead originated in North or Central America and reached South America with the first settlers. Coalescence age estimates for these subhaplogroups provide time boundaries indicating that early Paleo-Indians probably moved from North America to the area corresponding to modern Ecuador and Peru over the short time frame of ∼1.5 ka comprised between 16.0 and 14.6 ka.

Genetic and archaeological data indicate that the initial Paleoindian settlers of South America followed two entry routes separated by the Andes and the Amazon rainforest. The interactions between these paths and their impact on the peopling of South America remain unclear. Analysis of genetic variation in the Peruvian Andes and regions located south of the Amazon River might provide clues on this issue. We analyzed mitochondrial DNA variation at different Andean locations and >360,000 autosomal SNPs from 28 Native American ethnic groups to evaluate different trans-Andean demographic scenarios. Our data reveal that the Peruvian Altiplano was an important enclave for early Paleoindian expansions and point to a genetic continuity in the Andes until recent times, which was only marginally affected by gene flow from the Amazonian lowlands. Genomic variation shows a good fit with the archaeological evidence, indicating that the genetic interactions between the descendants of the settlers that followed the Pacific and Atlantic routes were extremely limited.

BackgroundGenetic studies support the scenario that Bos taurus domestication occurred in the Near East during the Neolithic transition about 10 thousand years (ky) ago, with the likely exception of a minor secondary event in Italy. However, despite the proven effectiveness of whole mitochondrial genome data in providing valuable information concerning the origin of taurine cattle, until now no population surveys have been carried out at the level of mitogenomes in local breeds from the Near East or surrounding areas. Egypt is in close geographic and cultural proximity to the Near East, in particular the Nile Delta region, and was one of the first neighboring areas to adopt the Neolithic package. Thus, a survey of mitogenome variation of autochthonous taurine breeds from the Nile Delta region might provide new insights on the early spread of cattle rearing outside the Near East.MethodologyUsing Illumina high-throughput sequencing we characterized the mitogenomes from two cattle breeds, Menofi (N = 17) and Domiaty (N = 14), from the Nile Delta region. Phylogenetic and Bayesian analyses were subsequently performed.ConclusionsPhylogenetic analyses of the 31 mitogenomes confirmed the prevalence of haplogroup T1, similar to most African cattle breeds, but showed also high frequencies for haplogroups T2, T3 and Q1, and an extremely high haplotype diversity, while Bayesian skyline plots pointed to a main episode of population growth ~12.5 ky ago. Comparisons of Nile Delta mitogenomes with those from other geographic areas revealed that (i) most Egyptian mtDNAs are probably direct local derivatives from the founder domestic herds which first arrived from the Near East and the extent of gene flow from and towards the Nile Delta region was limited after the initial founding event(s); (ii) haplogroup Q1 was among these founders, thus proving that it underwent domestication in the Near East together with the founders of the T clades.

Background Increasing evidence linking epigenetic mechanisms and different diseases, including cancer, has prompted in the last 15 years the investigation of histone post-translational modifications (PTMs) in clinical samples. Methods allowing the isolation of histones from patient samples followed by the accurate and comprehensive quantification of their PTMs by mass spectrometry (MS) have been developed. However, the applicability of these methods is limited by the requirement for substantial amounts of material. Results To address this issue, in this study we streamlined the protein extraction procedure from low-amount clinical samples and tested and implemented different in-gel digestion strategies, obtaining a protocol that allows the MS-based analysis of the most common histone PTMs from laser microdissected tissue areas containing as low as 1000 cells, an amount approximately 500 times lower than what is required by available methods. We then applied this protocol to breast cancer patient laser microdissected tissues in two proof-of-concept experiments, identifying differences in histone marks in heterogeneous regions selected by either morphological evaluation or MALDI MS imaging. Conclusions These results demonstrate that analyzing histone PTMs from very small tissue areas and detecting differences from adjacent tumor regions is technically feasible. Our method opens the way for spatial epi-proteomics, namely the investigation of epigenetic features in the context of tissue and tumor heterogeneity, which will be instrumental for the identification of novel epigenetic biomarkers and aberrant epigenetic mechanisms.

Genome integrity is continuously threatened by endogenous sources of DNA damage including reactive oxygen species (ROS) produced by cell metabolism. Factors of the RNA interference (RNAi) machinery have been recently involved in the cellular response to DNA damage (DDR) in proliferating cells. To investigate the impact of component of RNAi machinery on DDR activation in terminally differentiated cells, we exploited cytoplasmic hybrid (cybrid) cell lines in which mitochondria of sporadic Parkinson’s disease patients repopulate neuroblastoma SH-SY5Y-Rho(0) cells. Upon differentiation into dopaminergic neuron-like cells, PD63 cybrid showed increased intracellular level of ROS and chronic DDR activation, compared to other cybrids with the same nuclear background. Importantly, DDR activation in these cells can be prevented by ROS scavenging treatment suggesting that ROS production is indeed causative of nuclear DNA damage. Sequence analysis of the mitogenomes identified a rare and heteroplasmic missense mutation affecting a highly conserved residue of the ND5-subunit of respiratory complex I, which accounts for ROS increase. We demonstrated that the assembly of nuclear DDR foci elicited by oxidative stress in these cells relies on DROSHA, providing the first evidence that components of RNAi machinery play a crucial role also in the mounting of ROS-induced DDR in non-replicating neuronal cells.

Rare mitochondrial lineages with relict distributions can sometimes be disproportionately informative about deep events in human prehistory. We have studied one such lineage, haplogroup R0a, which uniquely is most frequent in Arabia and the Horn of Africa, but is distributed much more widely, from Europe to India. We conclude that: (1) the lineage ancestral to R0a is more ancient than previously thought, with a relict distribution across the Mediterranean/Southwest Asia; (2) R0a has a much deeper presence in Arabia than previously thought, highlighting the role of at least one Pleistocene glacial refugium, perhaps on the Red Sea plains; (3) the main episode of dispersal into Eastern Africa, at least concerning maternal lineages, was at the end of the Late Glacial, due to major expansions from one or more refugia in Arabia; (4) there was likely a minor Late Glacial/early postglacial dispersal from Arabia through the Levant and into Europe, possibly alongside other lineages from a Levantine refugium; and (5) the presence of R0a in Southwest Arabia in the Holocene at the nexus of a trading network that developed after ~3 ka between Africa and the Indian Ocean led to some gene flow even further afield, into Iran, Pakistan and India.