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Here we demonstrate that human neural stem cells (NSCs) proliferate while in space and they express specific NSC markers after being in space. NSCs displayed both higher oxygen consumption and glycolysis than ground controls. These cells also kept their ability to become young neurons. Electrophysiological recordings of space NSC-derived neurons showed immature cell membrane properties characterized by small capacitance and very high input resistance. Current injections elicited only an incipient action potential. No spontaneous synaptic events could be detected, suggesting their immature status even though most recorded cells displayed complex morphology and numerous cell processes. Ascertaining the origin of the NSCs’ increased energy requirement is of the essence in order to design effective measures to minimize health risks associated with long-duration human spaceflight missions.

Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL-fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate-day administration of IMPDH inhibitors suppressed the development of MLL-AF9-driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll-like receptor (TLR)-TRAF6-NF-κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL-fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL-fusion AMLs and potentially other aggressive tumors with active TLR signaling., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Pests appear to have accompanied humans and their crops since the beginning of farming. Nevertheless, their study is only rarely integrated into research on farming in prehistory. An assemblage of invertebrates and small mammals was recovered from the waterlogged layers of three wells at the Middle Neolithic site (4250-3700 cal B.C.) of Les Bagnoles (SE France). The microfaunal remains were retrieved from sediment samples by wet sieving (wash-over technique). The most common among the rodents is the wood mouse. The assemblage also consists of insect remains of grain weevil, seed beetle, and corn ground beetle. The different finds not only offer data on the role of insect and rodent pests in the Neolithic but on the possible strategies adopted by the early farming communities in the western Mediterranean in response to pest infestation. The findings appear to confirm the hypothesis that the wood mouse was a commensal and storage pest in settlements long before the arrival of the invasive house mouse during the Bronze Age. The presence of the main storage pest, the grain weevil, suggests a long-term grain storage issue at Les Bagnoles. The combination of the results of the site's archaeobotanical findings with those of other sites in the western Mediterranean suggests that the shift from naked to glume wheat around 4000 B.C. may also stem from a reaction to the problem of grain weevil infestation.

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (≥1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modern legacy of past equestrian civilizations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modern breeding impacted genetic diversity more dramatically than the previous millennia of human management., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Transcription factor RUNX1 plays a crucial role in hematopoiesis and its activity is tightly regulated at both the transcriptional and posttranslational levels. However, translational control of RUNX1 expression has not been fully understood. In this study, we demonstrated that RUNX1b mRNA is translated from two alternative initiation sites, Met-1 and Met-25, giving full-length RUNX1b and a shorter protein lacking the first 24 amino acids (RUNX1ΔN24). Presence/absence of strong Kozak consensus sequences around Met-1 determines which initiation site is mainly used in RUNX1b cDNA. Selective disruption of either Met-1 or Met-25 abrogates expression of the corresponding protein while facilitating the production of another protein. The RUNX1b cDNA containing 65bp natural promoter sequences mainly produces full-length RUNX1b in human cord blood cells, but disruption of Met-1 in this cDNA also induced translation from Met-25. Consistent with these data, disruption of endogenous RUNX1b around Met-1 using CRISPR/Cas9 induced selective expression of RUNX1ΔΝ24 in several leukemia cell lines. RUNX1ΔN24 protein is more stable than full-length RUNX1b and retains hematopoietic activity. We also found that FLAG-tagged full-length RUNX1 showed altered activity, indicating the influence of N-terminal FLAG-tag on RUNX1 function. The alternative translation initiation of RUNX1b may participate in fine tuning RUNX1 activity., (Copyright © 2019. Published by Elsevier Inc.)

[This corrects the article DOI: 10.1371/journal.pone.0189278.].

To date, osteometric data for Swiss Bronze Age cattle, particularly from Alpine sites, are scarce. In the present study, using a large dataset generated by combining preexisting data with recent data obtained from a large Alpine site, cattle size from the Late Neolithic to the Late Bronze Age (LBA) in populations from different sites and regions was evaluated using the logarithmic size index and other statistical analysis. Additionally, the finite mixture model and a meta-analytic technique were used to observe possible effects of sex ratios on cattle size. Results indicated that sex ratios did not affect size distribution. Cattle populations did not differ over time, but the Alpine cattle were smaller than the Central Plateau cattle. There were two distinct sizes in the Alpine cattle populations. It is suggested that the different economic interrelationships between Alpine and other geographically related communities might have led to the emergence of size diversity in Swiss Bronze Age cattle. Further interdisciplinary studies with larger sample sizes are required to confirm these possibilities.

In north-eastern France, red deer (Cervus elaphus L.) populations were rebuilt from a few hundred individuals, which have subsisted in remote valleys of the Vosges mountains, and to a lesser extent from individuals escaped from private enclosures; at present times, this species occupies large areas, mainly in the Vosges Mountains. In this study, we examined the population dynamics of red deer in the Vosges Mountains using ancient and contemporary mitochondrial DNA (mtDNA) from 140 samples (23 ancient + 117 modern) spanning the last 7'000 years. In addition, we reconstructed the feeding habits and the habitat of red deer since the beginning of agriculture applying isotopic analyses in order to establish a basis for current environmental management strategies. We show that past and present red deer in the Vosges Mountains belong to mtDNA haplogroup A, suggesting that they originated from the Iberian refugium after the last glacial maximum (LGM). Palaeogenetic analysis of ancient bone material revealed the presence of two distinct haplotypes with different temporal distributions. Individuals belonging to the two haplotype groups apparently occupied two different habitats over at least 7'000 years. AM6 correlates with an ecological type that feeds in densely forested mountain landscapes, while AM235 correlates with feeding in lowland landscapes, composed of a mixture of meadows and riverine, herb-rich woodlands. Our results suggest that red deer of north-eastern France was able to adapt, over the long term, to these different habitat types, possibly due to efficient ethological barriers. Modern haplotype patterns support the historical record that red deer has been exposed to strong anthropogenic influences as a major game species.

Reconstructing stock herding strategies and land use is key to comprehending past human social organization and economy. We present laser-ablation strontium and carbon isotope data from 25 cattle (Bos taurus) to reconstruct mobility and infer herding management at the Swiss lakeside settlement of Arbon Bleiche 3, occupied for only 15 years (3384-3370 BC). Our results reveal three distinct isotopic patterns that likely reflect different herding strategies: 1) localized cattle herding, 2) seasonal movement, and 3) herding away from the site year-round. Different strategies of herding are not uniformly represented in various areas of the settlement, which indicates specialist modes of cattle management. The pressure on local fodder capacities and the need for alternative herding regimes must have involved diverse access to grazing resources. Consequently, the increasing importance of cattle in the local landscape was likely to have contributed to the progress of socio-economic differentiation in early agricultural societies in Europe.

On large geographical scales, changes in animal population distribution and abundance are driven by environmental change due to climatic and anthropogenic processes. However, so far, little is known about population dynamics on a regional scale. We have investigated 92 archaeological horse remains from nine sites mainly adjacent to the Swiss Jura Mountains dating from c. 41,000-5,000 years BP. The time frame includes major environmental turning points such as the Last Glacial Maximum (LGM), followed by steppe vegetation, afforestation and initial re-opening of the landscape by human agricultural activities. To investigate matrilinear population dynamics, we assembled 240 base pairs of the mitochondrial d-loop. FST values indicate large genetic differentiation of the horse populations that were present during and directly after the LGM. After the retreat of the ice, a highly diverse population expanded as demonstrated by significantly negative results for Tajima's D, Fu's FS and mismatch analyses. At the same time, a different development took place in Asia where populations declined after the LGM. This first comprehensive investigation of wild horse remains on a regional scale reveals a discontinuous colonisation of succeeding populations, a pattern that diverges from the larger Eurasian trend.

Eradication of leukemia stem cells (LSCs) is the ultimate goal of treating acute myeloid leukemia (AML). We recently showed that the combined loss of Runx1/Cbfb inhibited the development of MLL-AF9-induced AML. However, c-Kit + /Gr-1 - cells remained viable in Runx1/Cbfb-deleted cells, indicating that suppressing RUNX activity may not eradicate the most immature LSCs. In this study, we found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor PAR-1 (protease-activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells. Similar to the effect of Runx1/Cbfb deletion, PAR-1 overexpression induced CDKN1A/p21 expression and attenuated proliferation in MLL-AF9 cells. To our surprise, PAR-1 deficiency also prevented leukemia development induced by a small number of MLL-AF9 leukemia stem cells (LSCs) in vivo. PAR-1 deficiency also reduced leukemogenicity of AML1-ETO-induced leukemia. Re-expression of PAR-1 in PAR-1-deficient cells combined with a limiting-dilution transplantation assay demonstrated the cell-dose-dependent role of PAR-1 in MLL-AF9 leukemia: PAR-1 inhibited rapid leukemic proliferation when there were a large number of LSCs, while a small number of LSCs required PAR-1 for their efficient growth. Mechanistically, PAR-1 increased the adherence properties of MLL-AF9 cells and promoted their engraftment to bone marrow. Taken together, these data revealed a multifaceted role for PAR-1 in leukemogenesis, and highlight this receptor as a potential target to eradicate primitive LSCs in AML.

Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog. In primary human MM samples, increased glycolytic gene expression correlated with poorer overall and event-free survival outcomes. Notably, stem-like cells showed increased mitochondrial mass, rhodamine 123 accumulation, and orthodox mitochondrial configuration while more condensed mitochondria were noted in the CD138high cells. Glycolytic inhibitor 2-deoxyglucose (2-DG) induced ER stress as detected by qPCR (BiP, ATF4) and immunoblotting (BiP, CHOP) and increased dihydroethidium probe oxidation both CD138low and CD138high cells. Treatment with a mitochondrial-targeting agent decyl-triphenylphosphonium (10-TPP) increased intracellular steady-state pro-oxidant levels in stem-like and mature MM cells. Furthermore, 10-TPP mediated increases in mitochondrial oxidant production were suppressed by ectopic expression of manganese superoxide dismutase. Relative to 2-DG or 10-TPP alone, 2-DG plus 10-TPP combination showed increased caspase 3 activation in MM cells with minimal toxicity to the normal hematopoietic progenitor cells. Notably, treatment with polyethylene glycol conjugated catalase significantly reduced 2-DG and/or 10-TPP-induced apoptosis of MM cells. Also, the combination of 2-DG with 10-TPP decreased clonogenic survival of MM cells. Taken together, this study provides a novel strategy of metabolic oxidative stress-induced cytotoxicity of MM cells via 2-DG and 10-TPP combination therapy., Competing Interests: The authors have declared that no competing interests exist.

The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Domestication is an ongoing process continuously changing the lives of animals and humans and the environment. For the majority of European cattle (Bos taurus) genetic and archaeozoological evidence support initial domestication ca. 11'000 BP in the Near East from few founder aurochs (Bos primigenius) belonging to the mitochondrial DNA T macro-haplogroup. Gene flow between wild European aurochs of P haplogroup and domestic cattle of T haplogroup, coexisting over thousands of years, appears to have been sporadic. We report archaeozoological and ancient DNA evidence for the incorporation of wild stock into a domestic cattle herd from a Neolithic lake-dwelling in Switzerland. A complete metacarpus of a small and compact adult bovid is morphologically and genetically a female. With withers height of ca. 112 cm, it is comparable in size with small domestic cattle from contemporaneous sites in the area. The bone is directly dated to 3360-3090 cal BC and associated to the Horgen culture, a period of the secondary products revolution. The cow possessed a novel mtDNA P haplotype variant of the European aurochs. We argue this is either a single event or, based on osteological characteristics of the Horgen cattle, a rare instance of intentional breeding with female aurochs.

RUNX1 is generally considered a tumor suppressor in myeloid neoplasms. Inactivating RUNX1 mutations have frequently been found in patients with myelodysplastic syndrome (MDS) and cytogenetically normal acute myeloid leukemia (AML). However, no somatic RUNX1 alteration was found in AMLs with leukemogenic fusion proteins, such as core-binding factor (CBF) leukemia and MLL fusion leukemia, raising the possibility that RUNX1 could actually promote the growth of these leukemia cells. Using normal human cord blood cells and those expressing leukemogenic fusion proteins, we discovered a dual role of RUNX1 in myeloid leukemogenesis. RUNX1 overexpression inhibited the growth of normal cord blood cells by inducing myeloid differentiation, whereas a certain level of RUNX1 activity was required for the growth of AML1-ETO and MLL-AF9 cells. Using a mouse genetic model, we also showed that the combined loss of Runx1/Cbfb inhibited leukemia development induced by MLL-AF9. RUNX2 could compensate for the loss of RUNX1. The survival effect of RUNX1 was mediated by BCL2 in MLL fusion leukemia. Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a promising therapeutic strategy for AMLs with leukemogenic fusion proteins.

This study evaluates the role of scavenger receptor class A member 3 (SCARA3) in multiple myeloma (MM). SCARA3 expression was induced upon treatment with oxidative stressors (ionizing radiation and chemotherapeutic drugs). An epigenetic inactivation of SCARA3 was noted in MM.1S myeloma cells. Myeloma cell killing by dexamethasone and bortezomib was inhibited by up-regulation of SCARA3 while SCARA3 knockdown sensitized myeloma cells to the drugs. Clinical samples showed an inverse correlation between SCARA3 gene expression, myeloma progression, and favorable clinical prognosis. In MM, SCARA3 protects against oxidative stress-induced cell killing and can serve as predictor of MM progression and therapeutic response., (Published by Elsevier Ltd.)

The nuclear factor (NF)-κB signaling pathway is critical in myeloma cell proliferation, inhibition of apoptosis, and emergence of therapy resistance. The chemotherapeutic drugs, dexamethasone (Dex) and bortezomib (BTZ), are widely used in clinical protocols for multiple myeloma (MM) and inhibit the NF-κB signaling pathway by distinct mechanisms. This study evaluates the efficacy of combination therapy with Dex and BTZ and investigates the mechanistic underpinning of endogenous and therapy-induced NF-κB activation in MM. Human myeloma cells and bone marrow stromal cells (BMSCs) were used in monocultures and cocultures to determine the cytotoxic effects of Dex and/or BTZ. Our results show that combined treatment of Dex with BTZ enhanced direct apoptosis of drug-sensitive and drug-resistant myeloma cells. In the presence of BMSCs, Dex plus BTZ combination inhibited ionizing radiation-induced interleukin 6 secretion from BMSCs and induced myeloma cytotoxicity. Mechanistically, Dex treatment increased IκBα protein and mRNA expression and compensated for BTZ-induced IκBα degradation. Dex plus BTZ combination inhibited basal and therapy-induced NF-κB activity with cytotoxicity in myeloma cells resistant to BTZ. Furthermore, combination therapy downregulated the NF-κB-targeted gene expression of interleukin 6 and manganese superoxide dismutase, which can induce chemo- and radio-resistance in MM. This study provides a mechanistic rationale for combining the NF-κB-targeting drugs Dex and BTZ in myeloma therapy and supports potential combinations of these drugs with radiotherapy and additional chemotherapeutic drugs for clinical benefit in MM., (Published by Elsevier Inc.)

The molecular and isotopic chemistry of organic residues from archaeological potsherds was used to obtain further insight into the dietary trends and economies at the Constance lake-shore Neolithic settlements. The archaeological organic residues from the Early Late Neolithic (3922-3902 BC) site Hornstaad-Hornle IA/Germany are, at present, the oldest archaeological samples analysed at the Institute of Mineralogy and Geochemistry of the University of Lausanne. The approach includes 13C/12C and 15N/14N ratios of the bulk organic residues, fatty acids distribution and 13C/12C ratios of individual fatty acids. The results are compared with those obtained from the over 500 years younger Neolithic (3384-3370 BC) settlement of Arbon Bleiche 3/Switzerland and with samples of modern vegetable oils and fat of animals that have been fed exclusively on C3 forage grasses. The overall fatty acid composition (C9 to C24 range, maximizing at C14 and C16), the bulk 13C/12C and 15N/14N ratios (delta13C, delta15N) and the 13C/12C ratios of palmitic (C16:0), stearic (C18:0) and oleic acids (C18:1) of the organic residues indicate that most of the studied samples (25 from 47 samples and 5 from 41 in the delta13C18:0 vs. delta13C16:0 and delta13C18:0 vs. delta13C18:1 diagrams, respectively) from Hornstaad-Hornle IA and Arbon Bleiche 3 sherds contain fat residues of pre-industrial ruminant milk, and young suckling calf/lamb adipose. These data provide direct proof of milk and meat (mainly from young suckling calves) consumption and farming practices for a sustainable dairying in Neolithic villages in central Europe around 4000 BC.dagger.

The Neolithic Revolution began 11,000 years ago in the Near East and preceded a westward migration into Europe of distinctive cultural groups and their agricultural economies, including domesticated animals and plants. Despite decades of research, no consensus has emerged about the extent of admixture between the indigenous and exotic populations or the degree to which the appearance of specific components of the "Neolithic cultural package" in Europe reflects truly independent development. Here, through the use of mitochondrial DNA from 323 modern and 221 ancient pig specimens sampled across western Eurasia, we demonstrate that domestic pigs of Near Eastern ancestry were definitely introduced into Europe during the Neolithic (potentially along two separate routes), reaching the Paris Basin by at least the early 4th millennium B.C. Local European wild boar were also domesticated by this time, possibly as a direct consequence of the introduction of Near Eastern domestic pigs. Once domesticated, European pigs rapidly replaced the introduced domestic pigs of Near Eastern origin throughout Europe. Domestic pigs formed a key component of the Neolithic Revolution, and this detailed genetic record of their origins reveals a complex set of interactions and processes during the spread of early farmers into Europe.

In Switzerland domestic cattle (Bos primigenius f. taurus resp. Bos taurus L.) first appear with the earliest Neolithic settlements (approximately 5000 BC). With the gradual deforestation of the landscape caused by human exploitation of the environment, cattle were used more intensive and in many ways. There is evidence that cattle were used as draught animal since ca. 3400 BC, probably even earlier milk was regularly used. The size of domestic cattle gradually decreased from Early Neolithic until Iron Age. Only with Roman influence larger animals are found. However, after the withdrawal of Romans the average size of cattle decreased again. Archaeogenetic studies will have to show, whether this is due to novel breeding strategies or the import of breeding stock. First genetic results showed that a female genetic type, which is rare in European breeds, is present in Swiss Evolène cattle and in one animal of Roman time cattle from Augusta Raurica. Is this a sign for influence of Roman cattle on today's Swiss breeds?

Typical Near East mitochondrial haplotypes of the T2 lineage were found in one cattle metacarpus sample from the Roman period and in two present-day Evolène cattle in Switzerland. Sequences from eight additional Evolène and four Raetian Grey aligned to the European haplotype T3. Analysis of nucleotide diversity within the mitochondrial D-loop of both studied Swiss cattle breeds revealed high haplotype diversity and similar diversity to a European cattle reference group. Mitochondrial T3 haplotypes radiated star-like from two similarly frequent haplotypes, possibly indicating two different expansion routes. The breed structure of Evolène cattle can be explained either by an introduction of diverse female lineages from the domestication centre or by later admixture. The introduction of the Near East lineage to Switzerland must have happened during the Roman time or earlier.