29 results on '"Bunce, M."'
Search Results
2. Scrapheap Challenge: A novel bulk-bone metabarcoding method to investigate ancient DNA in faunal assemblages
- Author
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Murray, D.C., Haile, J., Dortch, J., White, N.E., Haouchar, D., Bellgard, M.I., Allcock, R.J., Prideaux, G.J., Bunce, M., Murray, D.C., Haile, J., Dortch, J., White, N.E., Haouchar, D., Bellgard, M.I., Allcock, R.J., Prideaux, G.J., and Bunce, M.
- Abstract
Highly fragmented and morphologically indistinct fossil bone is common in archaeological and paleontological deposits but unfortunately it is of little use in compiling faunal assemblages. The development of a cost-effective methodology to taxonomically identify bulk bone is therefore a key challenge. Here, an ancient DNA methodology using high-throughput sequencing is developed to survey and analyse thousands of archaeological bones from southwest Australia. Fossils were collectively ground together depending on which of fifteen stratigraphical layers they were excavated from. By generating fifteen synthetic blends of bulk bone powder, each corresponding to a chronologically distinct layer, samples could be collectively analysed in an efficient manner. A diverse range of taxa, including endemic, extirpated and hitherto unrecorded taxa, dating back to c.46,000 years BP was characterized. The method is a novel, cost-effective use for unidentifiable bone fragments and a powerful molecular tool for surveying fossils that otherwise end up on the taxonomic “scrapheap”.
- Published
- 2013
3. Ancient human genome sequence of an extinct Palaeo-Eskimo
- Author
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Rasmussen, M., Li, Y., Lindgreen, S., Pedersen, J.S., Albrechtsen, A., Moltke, I., Metspalu, M., Metspalu, E., Kivisild, T., Gupta, R., Bertalan, M., Nielsen, K., Gilbert, M.T.P., Wang, Y., Raghavan, M., Campos, P.F., Kamp, H.M., Wilson, A.S., Gledhill, A., Tridico, S., Bunce, M., Lorenzen, E.D., Binladen, J., Guo, X., Zhao, J., Zhang, X., Zhang, H., Li, Z., Chen, M., Orlando, L., Kristiansen, K., Bak, M., Tommerup, N., Bendixen, C., Pierre, T.L., Grønnow, B., Meldgaard, M., Andreasen, C., Fedorova, S.A., Osipova, L.P., Higham, T.F.G., Ramsey, C.B., Hansen, T.O., Nielsen, F.C., Crawford, M.H., Brunak, S., Sicheritz-Pontén, T., Villems, R., Nielsen, R., Krogh, A., Wang, J., Willerslev, E., Rasmussen, M., Li, Y., Lindgreen, S., Pedersen, J.S., Albrechtsen, A., Moltke, I., Metspalu, M., Metspalu, E., Kivisild, T., Gupta, R., Bertalan, M., Nielsen, K., Gilbert, M.T.P., Wang, Y., Raghavan, M., Campos, P.F., Kamp, H.M., Wilson, A.S., Gledhill, A., Tridico, S., Bunce, M., Lorenzen, E.D., Binladen, J., Guo, X., Zhao, J., Zhang, X., Zhang, H., Li, Z., Chen, M., Orlando, L., Kristiansen, K., Bak, M., Tommerup, N., Bendixen, C., Pierre, T.L., Grønnow, B., Meldgaard, M., Andreasen, C., Fedorova, S.A., Osipova, L.P., Higham, T.F.G., Ramsey, C.B., Hansen, T.O., Nielsen, F.C., Crawford, M.H., Brunak, S., Sicheritz-Pontén, T., Villems, R., Nielsen, R., Krogh, A., Wang, J., and Willerslev, E.
- Abstract
We report here the genome sequence of an ancient human. Obtained from 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20Ã-, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
- Published
- 2010
4. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960
- Author
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Worobey, M., Gemmel, M., Teuwen, D.E., Haselkorn, T., Kunstman, K., Bunce, M., Muyembe, J-J, Kabongo, J.M., Kalengayi, R.M., Van Marck, E., Gilbert, M.T.P., Wolinsky, S.M., Worobey, M., Gemmel, M., Teuwen, D.E., Haselkorn, T., Kunstman, K., Bunce, M., Muyembe, J-J, Kabongo, J.M., Kalengayi, R.M., Van Marck, E., Gilbert, M.T.P., and Wolinsky, S.M.
- Abstract
Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Léopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods
- Published
- 2008
5. The phylogenetic position of the ‘giant deer’ Megaloceros giganteus
- Author
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Lister, A.M., Edwards, C.J., Nock, D.A.W., Bunce, M., van Pijlen, I.A., Bradley, D.G., Thomas, M.G., Barnes, I., Lister, A.M., Edwards, C.J., Nock, D.A.W., Bunce, M., van Pijlen, I.A., Bradley, D.G., Thomas, M.G., and Barnes, I.
- Abstract
The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers - the largest of any deer species, living or extinct - formed a focus of much past work 1-4. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer5-7. Recent morphological studies8, however, have challenged that view and placed the giant deer closer to the liying red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach.
- Published
- 2005
6. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA
- Author
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Kiepiela, P., Leslie, A.J., Honeyborne, I., Ramduth, D., Thobakgale, C., Chetty, S., Rathnavalu, P., Moore, C.B., Pfafferott, K.J., Hilton, L., Zimbwa, P., Moore, S., Allen, T., Brander, C., Addo, M.M., Altfeld, M., James, I., Mallal, S., Bunce, M., Barber, L.D., Szinger, J., Day, C., Klenerman, P., Mullins, J., Korber, B., Coovadia, H.M., Walker, B.D., Goulder, P.J.R., Kiepiela, P., Leslie, A.J., Honeyborne, I., Ramduth, D., Thobakgale, C., Chetty, S., Rathnavalu, P., Moore, C.B., Pfafferott, K.J., Hilton, L., Zimbwa, P., Moore, S., Allen, T., Brander, C., Addo, M.M., Altfeld, M., James, I., Mallal, S., Bunce, M., Barber, L.D., Szinger, J., Day, C., Klenerman, P., Mullins, J., Korber, B., Coovadia, H.M., Walker, B.D., and Goulder, P.J.R.
- Abstract
The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design
- Published
- 2004
7. Polymorphisms in tumour necrosis factor (TNF) are associated with risk of bladder cancer and grade of tumour at presentation
- Author
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Marsh, H.P., Haldar, N.A., Bunce, M., Marshall, S.E., le Monier, K., Winsey, S.L., Christodoulos, K., Cranston, D., Welsh, K.I., Harris, A.L., Marsh, H.P., Haldar, N.A., Bunce, M., Marshall, S.E., le Monier, K., Winsey, S.L., Christodoulos, K., Cranston, D., Welsh, K.I., and Harris, A.L.
- Abstract
The purpose of this study is to assess the role of tumour necrosis factor (TNF) polymorphisms in the risk of developing bladder cancer and effect on tumour stage, grade and progression. In all, seven single-nucleotide polymorphisms in TNF were studied in 196 bladder cancer patients and 208 controls using a PCR-SSP genotyping technique. It was seen that there was a significant association of two polymorphisms in TNF with bladder cancer: the TNF + 488A allele was found in 28.1% of patients compared with 14.9% of controls (P = 0.0012). In addition, TNF-859T was found in 26.0% of patients compared with 14.4% of the controls (P = 0.0036). The two loci were in tight linkage disequilibrium, that is, almost all the individuals having TNF + 488A also had TNF-859T. Patients with the TNF + 488A or TNF-859T were more likely to present with a moderately differentiated tumour than those patients without the uncommon allele. In all, 16.7% of patients with TNF + 488A and 29.9% of patients without TNF + 488A presented with a GI tumour (P = 0.015). A total of 14% of patients with TNF-859T and 30.5% of patients without TNF-859T presented with a GI tumour (P = 0.0043). There was no significant effect on time to first recurrence, stage progression or grade progression. In conclusion, a significant association between TNF polymorphisms TNF + 488A and TNF-859T and risk of bladder cancer was detected in this study. Both these polymorphisms were associated with grade of tumour at presentation although there was no significant effect on subsequent tumour behaviour.
- Published
- 2003
8. Extreme reversed sexual size dimorphism in the extinct New Zealand moa Dinornis
- Author
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Bunce, M., Worthy, T.H., Ford, T., Hoppitt, W., Willerslev, E., Drummond, A., Cooper, A., Bunce, M., Worthy, T.H., Ford, T., Hoppitt, W., Willerslev, E., Drummond, A., and Cooper, A.
- Abstract
The ratite moa (Aves; Dinornithiformes) were massive graviportal browsers weighing up to 250kg (ref. 1) that dominated the New Zealand biota until their extinction approximately 500yr ago. Despite an extensive Quaternary fossil record, moa taxonomy remains problematic 1-4 and currently 11 species are recognized. Three Dinornis species were found throughout New Zealand and differed markedly in size (1-2 m height at back) and mass (from ∼34 to 242kg)1. Surprisingly, ancient mitochondrial DNA sequences show that the three species were genetically indistinguishable within each island, but formed separate North and South Island clades. Here we show, using the first sex-linked nuclear sequences from an extinct species, that on each island the three morphological forms actually represent just one species, whose size varied markedly according to sex and habitat. The largest females in this example of extreme reversed sexual size dimorphism were about 280% the weight and 150% the height of the largest males, which is unprecedented among birds and terrestrial mammals. The combination of molecular and palaeontological data highlights the difficulties of analysing extinct groups, even those with detailed fossil records.
- Published
- 2003
9. Evolution and transmission of stable CTL escape mutations in HIV infection
- Author
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Goulder, P.J.R., Brander, C., Tang, Y., Tremblay, C., Colbert, R.A., Addo, M.M., Rosenberg, E.S., Nguyen, T.T., Allen, R., Trocha, A., Altfeld, M., He, S., Bunce, M., Funkhouser, R., Pelton, S.I., Burchett, S.K., McIntosh, K., Korber, B.T.M., Walker, B.D., Goulder, P.J.R., Brander, C., Tang, Y., Tremblay, C., Colbert, R.A., Addo, M.M., Rosenberg, E.S., Nguyen, T.T., Allen, R., Trocha, A., Altfeld, M., He, S., Bunce, M., Funkhouser, R., Pelton, S.I., Burchett, S.K., McIntosh, K., Korber, B.T.M., and Walker, B.D.
- Abstract
Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother–child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.
- Published
- 2001
10. Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency
- Author
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Mullighan, C.G., Marshall, S.E., Bunce, M., Mullighan, C.G., Marshall, S.E., and Bunce, M.
- Abstract
Variation in clinical phenotype is a hallmark of many complex diseases. The cause of this clinical heterogeneity is unknown, but it may be determined by genetic factors distinct from those conferring disease susceptibility. Common variable immunodeficiency (CVID) is a complex disease of unknown aetiology and diverse clinical manifestations. We have developed a unified polymerase chain reaction and sequence-specific primer (PCR-SSP) method to simultaneously genotype multiple polymorphisms under identical conditions, and have used this method to test the hypothesis that the clinical phenotype of CVID is determined by immunoregulatory gene polymorphism. Twenty-three polymorphisms in 13 genes were studied in 163 CVID patients. Vitamin D receptor and IL-6 alleles were associated with immunophenotypic abnormalities characteristic of more severe disease; and tumour necrosis factor and IL-10 alleles conferred susceptibility to the granulomatous form of CVID in an interacting fashion. These findings demonstrate that different clinical features of a disease may have unique pathogenetic abnormalities, determined by multiple interacting genetic factors. The ease of application of this efficient, robust genotyping technique to polymorphisms throughout the genome will make it a powerful tool in the investigation of the genetic basis of phenotypic variability in a wide variety of diseases.
- Published
- 1999
11. HLA-CW*0602 is a susceptibility factor in Type I psoriasis, and evidence Ala-73 is increased in Male Type I psoriatics
- Author
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Mallon, E., Bunce, M., Wojnarowska, F., Welsh, K.I., Mallon, E., Bunce, M., Wojnarowska, F., and Welsh, K.I.
- Abstract
We investigated the HLA-C locus of 87 unrelated patients with chronic plaque psoriasis by genotyping with sequence-specifc amplification printers. The HLA-Cw*0602 allele was significantly increased in male and female type I psoriatics but not significantly increased in either male or female type II psoriatics. The overall frequency of Ala-73 (present in Cw*04, Cw*0602, Cw*07, Cw*12, Cw*1503, and Cw*17) in psoriatics was 88.5% but the incidence of Ala-73 in our Caucasian controls was also high at 84.3%. Ala-73 was present in 97.2% of type I and 85.7% of type II male psoriatics (chi² = 8.43, p = 0.001; chi² = 0.01, p = nonsignificant, respectively), in contrast to 81.5% of type I and 80% of type II female psoriatics (nonsignificant). HLA-Cw*0602 appeared more discriminating in determining disease susceptibility in our population than Ala-73, in line with earlier serologic studies implicating HLA-Cw6. Thus, although the frequency of HLA-Cw*0602 decreased from 54.0% in type I to 29.2% in type II psoriatics, the overall frequency of Ala-73, present in 90.4% of type I and 83.3% of type II psoriatics, did not. (i) Thus this study confirms the strong association between psoriasis and HLA-Cw*0602 by using sequence-specific amplification primers. (ii) Results show that Ala-73 on HLA-C molecules is increased in frequency in psoriasis, but results observed show an association more subtle than previously thought, with HLA-Cw*0602 playing the major role. (iii) This report documents the differential association of HLA genes in male and female psoriatic patients. An interaction between gender and immunogenetics may influence susceptibility to psoriasis.
- Published
- 1997
12. Author Correction: Dense sampling of bird diversity increases power of comparative genomics.
- Author
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Feng S, Stiller J, Deng Y, Armstrong J, Fang Q, Reeve AH, Xie D, Chen G, Guo C, Faircloth BC, Petersen B, Wang Z, Zhou Q, Diekhans M, Chen W, Andreu-Sánchez S, Margaryan A, Howard JT, Parent C, Pacheco G, Sinding MS, Puetz L, Cavill E, Ribeiro ÂM, Eckhart L, Fjeldså J, Hosner PA, Brumfield RT, Christidis L, Bertelsen MF, Sicheritz-Ponten T, Tietze DT, Robertson BC, Song G, Borgia G, Claramunt S, Lovette IJ, Cowen SJ, Njoroge P, Dumbacher JP, Ryder OA, Fuchs J, Bunce M, Burt DW, Cracraft J, Meng G, Hackett SJ, Ryan PG, Jønsson KA, Jamieson IG, da Fonseca RR, Braun EL, Houde P, Mirarab S, Suh A, Hansson B, Ponnikas S, Sigeman H, Stervander M, Frandsen PB, van der Zwan H, van der Sluis R, Visser C, Balakrishnan CN, Clark AG, Fitzpatrick JW, Bowman R, Chen N, Cloutier A, Sackton TB, Edwards SV, Foote DJ, Shakya SB, Sheldon FH, Vignal A, Soares AER, Shapiro B, González-Solís J, Ferrer-Obiol J, Rozas J, Riutort M, Tigano A, Friesen V, Dalén L, Urrutia AO, Székely T, Liu Y, Campana MG, Corvelo A, Fleischer RC, Rutherford KM, Gemmell NJ, Dussex N, Mouritsen H, Thiele N, Delmore K, Liedvogel M, Franke A, Hoeppner MP, Krone O, Fudickar AM, Milá B, Ketterson ED, Fidler AE, Friis G, Parody-Merino ÁM, Battley PF, Cox MP, Lima NCB, Prosdocimi F, Parchman TL, Schlinger BA, Loiselle BA, Blake JG, Lim HC, Day LB, Fuxjager MJ, Baldwin MW, Braun MJ, Wirthlin M, Dikow RB, Ryder TB, Camenisch G, Keller LF, DaCosta JM, Hauber ME, Louder MIM, Witt CC, McGuire JA, Mudge J, Megna LC, Carling MD, Wang B, Taylor SA, Del-Rio G, Aleixo A, Vasconcelos ATR, Mello CV, Weir JT, Haussler D, Li Q, Yang H, Wang J, Lei F, Rahbek C, Gilbert MTP, Graves GR, Jarvis ED, Paten B, and Zhang G
- Published
- 2021
- Full Text
- View/download PDF
13. Angular momentum generation in nuclear fission.
- Author
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Wilson JN, Thisse D, Lebois M, Jovančević N, Gjestvang D, Canavan R, Rudigier M, Étasse D, Gerst RB, Gaudefroy L, Adamska E, Adsley P, Algora A, Babo M, Belvedere K, Benito J, Benzoni G, Blazhev A, Boso A, Bottoni S, Bunce M, Chakma R, Cieplicka-Oryńczak N, Courtin S, Cortés ML, Davies P, Delafosse C, Fallot M, Fornal B, Fraile L, Gottardo A, Guadilla V, Häfner G, Hauschild K, Heine M, Henrich C, Homm I, Ibrahim F, Iskra ŁW, Ivanov P, Jazrawi S, Korgul A, Koseoglou P, Kröll T, Kurtukian-Nieto T, Le Meur L, Leoni S, Ljungvall J, Lopez-Martens A, Lozeva R, Matea I, Miernik K, Nemer J, Oberstedt S, Paulsen W, Piersa M, Popovitch Y, Porzio C, Qi L, Ralet D, Regan PH, Rezynkina K, Sánchez-Tembleque V, Siem S, Schmitt C, Söderström PA, Sürder C, Tocabens G, Vedia V, Verney D, Warr N, Wasilewska B, Wiederhold J, Yavahchova M, Zeiser F, and Ziliani S
- Abstract
When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning
1 ; this phenomenon has been a mystery in nuclear physics for over 40 years2,3 . The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4-12 . Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14 , for the study of the structure of neutron-rich isotopes15,16 , and for the synthesis and stability of super-heavy elements17,18 .- Published
- 2021
- Full Text
- View/download PDF
14. Under the karst: detecting hidden subterranean assemblages using eDNA metabarcoding in the caves of Christmas Island, Australia.
- Author
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West KM, Richards ZT, Harvey ES, Susac R, Grealy A, and Bunce M
- Subjects
- Animals, Australia, Cell Nucleus genetics, Eukaryota genetics, Indian Ocean, Mitochondria genetics, RNA, Ribosomal, 16S genetics, Biodiversity, DNA Barcoding, Taxonomic methods, DNA, Environmental genetics, Metagenomics methods
- Abstract
Subterranean ecosystems are understudied and challenging to conventionally survey given the inaccessibility of underground voids and networks. In this study, we conducted a eukaryotic environmental DNA (eDNA) metabarcoding survey across the karst landscape of Christmas Island, (Indian Ocean, Australia) to evaluate the utility of this non-invasive technique to detect subterranean aquatic 'stygofauna' assemblages. Three metabarcoding assays targeting the mitochondrial 16S rRNA and nuclear 18S genes were applied to 159 water and sediment samples collected from 23 caves and springs across the island. Taken together, our assays detected a wide diversity of chordates, cnidarians, porifera, arthropods, molluscs, annelids and bryozoans from 71 families across 60 orders. We report a high level of variation between cave and spring subterranean community compositions which are significantly influenced by varying levels of salinity. Additionally, we show that dissolved oxygen and longitudinal gradients significantly affect biotic assemblages within cave communities. Lastly, we combined eDNA-derived community composition and environmental (water quality) data to predict potential underground interconnectivity across Christmas Island. We identified three cave and spring groups that showed a high degree of biotic and abiotic similarity indicating likely local connectivity. This study demonstrates the applicability of eDNA metabarcoding to detect subterranean eukaryotic communities and explore underground interconnectivity.
- Published
- 2020
- Full Text
- View/download PDF
15. Dense sampling of bird diversity increases power of comparative genomics.
- Author
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Feng S, Stiller J, Deng Y, Armstrong J, Fang Q, Reeve AH, Xie D, Chen G, Guo C, Faircloth BC, Petersen B, Wang Z, Zhou Q, Diekhans M, Chen W, Andreu-Sánchez S, Margaryan A, Howard JT, Parent C, Pacheco G, Sinding MS, Puetz L, Cavill E, Ribeiro ÂM, Eckhart L, Fjeldså J, Hosner PA, Brumfield RT, Christidis L, Bertelsen MF, Sicheritz-Ponten T, Tietze DT, Robertson BC, Song G, Borgia G, Claramunt S, Lovette IJ, Cowen SJ, Njoroge P, Dumbacher JP, Ryder OA, Fuchs J, Bunce M, Burt DW, Cracraft J, Meng G, Hackett SJ, Ryan PG, Jønsson KA, Jamieson IG, da Fonseca RR, Braun EL, Houde P, Mirarab S, Suh A, Hansson B, Ponnikas S, Sigeman H, Stervander M, Frandsen PB, van der Zwan H, van der Sluis R, Visser C, Balakrishnan CN, Clark AG, Fitzpatrick JW, Bowman R, Chen N, Cloutier A, Sackton TB, Edwards SV, Foote DJ, Shakya SB, Sheldon FH, Vignal A, Soares AER, Shapiro B, González-Solís J, Ferrer-Obiol J, Rozas J, Riutort M, Tigano A, Friesen V, Dalén L, Urrutia AO, Székely T, Liu Y, Campana MG, Corvelo A, Fleischer RC, Rutherford KM, Gemmell NJ, Dussex N, Mouritsen H, Thiele N, Delmore K, Liedvogel M, Franke A, Hoeppner MP, Krone O, Fudickar AM, Milá B, Ketterson ED, Fidler AE, Friis G, Parody-Merino ÁM, Battley PF, Cox MP, Lima NCB, Prosdocimi F, Parchman TL, Schlinger BA, Loiselle BA, Blake JG, Lim HC, Day LB, Fuxjager MJ, Baldwin MW, Braun MJ, Wirthlin M, Dikow RB, Ryder TB, Camenisch G, Keller LF, DaCosta JM, Hauber ME, Louder MIM, Witt CC, McGuire JA, Mudge J, Megna LC, Carling MD, Wang B, Taylor SA, Del-Rio G, Aleixo A, Vasconcelos ATR, Mello CV, Weir JT, Haussler D, Li Q, Yang H, Wang J, Lei F, Rahbek C, Gilbert MTP, Graves GR, Jarvis ED, Paten B, and Zhang G
- Subjects
- Animals, Chickens genetics, Conservation of Natural Resources, Datasets as Topic, Finches genetics, Humans, Selection, Genetic genetics, Synteny genetics, Birds classification, Birds genetics, Genome genetics, Genomics methods, Genomics standards, Phylogeny
- Abstract
Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity
1-4 . Sparse taxon sampling has previously been proposed to confound phylogenetic inference5 , and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.- Published
- 2020
- Full Text
- View/download PDF
16. Environmental DNA can act as a biodiversity barometer of anthropogenic pressures in coastal ecosystems.
- Author
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DiBattista JD, Reimer JD, Stat M, Masucci GD, Biondi P, De Brauwer M, Wilkinson SP, Chariton AA, and Bunce M
- Subjects
- Coral Reefs, DNA Barcoding, Taxonomic, DNA, Environmental isolation & purification, DNA, Ribosomal Spacer genetics, DNA, Ribosomal Spacer isolation & purification, Genetic Markers genetics, Oceans and Seas, RNA, Ribosomal, 18S genetics, Seawater, Spatio-Temporal Analysis, Biodiversity, Biota genetics, DNA, Environmental genetics, Environmental Monitoring methods
- Abstract
Loss of biodiversity from lower to upper trophic levels reduces overall productivity and stability of coastal ecosystems in our oceans, but rarely are these changes documented across both time and space. The characterisation of environmental DNA (eDNA) from sediment and seawater using metabarcoding offers a powerful molecular lens to observe marine biota and provides a series of 'snapshots' across a broad spectrum of eukaryotic organisms. Using these next-generation tools and downstream analytical innovations including machine learning sequence assignment algorithms and co-occurrence network analyses, we examined how anthropogenic pressures may have impacted marine biodiversity on subtropical coral reefs in Okinawa, Japan. Based on 18 S ribosomal RNA, but not ITS2 sequence data due to inconsistent amplification for this marker, as well as proxies for anthropogenic disturbance, we show that eukaryotic richness at the family level significantly increases with medium and high levels of disturbance. This change in richness coincides with compositional changes, a decrease in connectedness among taxa, an increase in fragmentation of taxon co-occurrence networks, and a shift in indicator taxa. Taken together, these findings demonstrate the ability of eDNA to act as a barometer of disturbance and provide an exemplar of how biotic networks and coral reefs may be impacted by anthropogenic activities.
- Published
- 2020
- Full Text
- View/download PDF
17. Partitioning of diet between species and life history stages of sympatric and cryptic snappers (Lutjanidae) based on DNA metabarcoding.
- Author
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Takahashi M, DiBattista JD, Jarman S, Newman SJ, Wakefield CB, Harvey ES, and Bunce M
- Subjects
- Animals, DNA analysis, Ecosystem, Fishes growth & development, Predatory Behavior, Sequence Analysis, DNA, Species Specificity, Sympatry, DNA genetics, DNA Barcoding, Taxonomic, Diet statistics & numerical data, Fishes classification, Fishes genetics, Gastrointestinal Tract metabolism, Genetic Speciation
- Abstract
Lutjanus erythropterus and L. malabaricus are sympatric, sister taxa that are important to fisheries throughout the Indo-Pacific. Their juveniles are morphologically indistinguishable (i.e. cryptic). A DNA metabarcoding dietary study was undertaken to assess the diet composition and partitioning between the juvenile and adult life history stages of these two lutjanids. Major prey taxa were comprised of teleosts and crustaceans for all groups except adult L. erythropterus, which instead consumed soft bodied invertebrates (e.g. tunicates, comb jellies and medusae) as well as teleosts, with crustaceans being notably absent. Diet composition was significantly different among life history stages and species, which may be associated with niche habitat partitioning or differences in mouth morphology within adult life stages. This study provides the first evidence of diet partitioning between cryptic juveniles of overlapping lutjanid species, thus providing new insights into the ecological interactions, habitat associations, and the specialised adaptations required for the coexistence of closely related species. This study has improved our understanding of the differential contributions of the juvenile and adult diets of these sympatric species within food webs. The diet partitioning reported in this study was only revealed by the taxonomic resolution provided by the DNA metabarcoding approach and highlights the potential utility of this method to refine the dietary components of reef fishes more generally.
- Published
- 2020
- Full Text
- View/download PDF
18. Author Correction: Early Pastoral Economies and Herding Transitions in Eastern Eurasia.
- Author
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Taylor WTT, Clark J, Bayarsaikhan J, Tuvshinjargal T, Jobe JT, Fitzhugh W, Kortum R, Spengler RN 3rd, Shnaider S, Seersholm FV, Hart I, Case N, Wilkin S, Hendy J, Thuering U, Miller B, Miller ARV, Picin A, Vanwezer N, Irmer F, Brown S, Abdykanova A, Shultz DR, Pham V, Bunce M, Douka K, Jones EL, and Boivin N
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
- Full Text
- View/download PDF
19. Early Pastoral Economies and Herding Transitions in Eastern Eurasia.
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Taylor WTT, Clark J, Bayarsaikhan J, Tuvshinjargal T, Jobe JT, Fitzhugh W, Kortum R, Spengler RN 3rd, Shnaider S, Seersholm FV, Hart I, Case N, Wilkin S, Hendy J, Thuering U, Miller B, Miller ARV, Picin A, Vanwezer N, Irmer F, Brown S, Abdykanova A, Shultz DR, Pham V, Bunce M, Douka K, Jones EL, and Boivin N
- Abstract
While classic models for the emergence of pastoral groups in Inner Asia describe mounted, horse-borne herders sweeping across the Eurasian Steppes during the Early or Middle Bronze Age (ca. 3000-1500 BCE), the actual economic basis of many early pastoral societies in the region is poorly characterized. In this paper, we use collagen mass fingerprinting and ancient DNA analysis of some of the first stratified and directly dated archaeofaunal assemblages from Mongolia's early pastoral cultures to undertake species identifications of this rare and highly fragmented material. Our results provide evidence for livestock-based, herding subsistence in Mongolia during the late 3rd and early 2nd millennia BCE. We observe no evidence for dietary exploitation of horses prior to the late Bronze Age, ca. 1200 BCE - at which point horses come to dominate ritual assemblages, play a key role in pastoral diets, and greatly influence pastoral mobility. In combination with the broader archaeofaunal record of Inner Asia, our analysis supports models for widespread changes in herding ecology linked to the innovation of horseback riding in Central Asia in the final 2nd millennium BCE. Such a framework can explain key broad-scale patterns in the movement of people, ideas, and material culture in Eurasian prehistory.
- Published
- 2020
- Full Text
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20. Ecosystem biomonitoring with eDNA: metabarcoding across the tree of life in a tropical marine environment.
- Author
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Stat M, Huggett MJ, Bernasconi R, DiBattista JD, Berry TE, Newman SJ, Harvey ES, and Bunce M
- Subjects
- Animals, DNA analysis, DNA genetics, Seawater chemistry, Sensitivity and Specificity, Sequence Analysis, DNA, Tropical Climate, Aquatic Organisms classification, Aquatic Organisms genetics, Environmental Monitoring methods, Metagenomics methods
- Abstract
Effective marine management requires comprehensive data on the status of marine biodiversity. However, efficient methods that can document biodiversity in our oceans are currently lacking. Environmental DNA (eDNA) sourced from seawater offers a new avenue for investigating the biota in marine ecosystems. Here, we investigated the potential of eDNA to inform on the breadth of biodiversity present in a tropical marine environment. Directly sequencing eDNA from seawater using a shotgun approach resulted in only 0.34% of 22.3 million reads assigning to eukaryotes, highlighting the inefficiency of this method for assessing eukaryotic diversity. In contrast, using 'tree of life' (ToL) metabarcoding and 20-fold fewer sequencing reads, we could detect 287 families across the major divisions of eukaryotes. Our data also show that the best performing 'universal' PCR assay recovered only 44% of the eukaryotes identified across all assays, highlighting the need for multiple metabarcoding assays to catalogue biodiversity. Lastly, focusing on the fish genus Lethrinus, we recovered intra- and inter-specific haplotypes from seawater samples, illustrating that eDNA can be used to explore diversity beyond taxon identifications. Given the sensitivity and low cost of eDNA metabarcoding we advocate this approach be rapidly integrated into biomonitoring programs.
- Published
- 2017
- Full Text
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21. Efficient Generation of Bispecific Murine Antibodies for Pre-Clinical Investigations in Syngeneic Rodent Models.
- Author
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Labrijn AF, Meesters JI, Bunce M, Armstrong AA, Somani S, Nesspor TC, Chiu ML, Altintaş I, Verploegen S, Schuurman J, and Parren PWHI
- Subjects
- Animals, Antibodies, Bispecific immunology, Humans, Immunoglobulin G genetics, Immunoglobulin G therapeutic use, Mice, Models, Animal, Neoplasms genetics, Neoplasms immunology, Point Mutation genetics, Point Mutation immunology, Rats, Xenograft Model Antitumor Assays, Antibodies, Bispecific biosynthesis, Immunoglobulin G immunology, Neoplasms therapy
- Abstract
Therapeutic concepts exploiting tumor-specific antibodies are often established in pre-clinical xenograft models using immuno-deficient mice. More complex therapeutic paradigms, however, warrant the use of immuno-competent mice, that more accurately capture the relevant biology that is being exploited. These models require the use of (surrogate) mouse or rat antibodies to enable optimal interactions with murine effector molecules. Immunogenicity is furthermore decreased, allowing longer-term treatment. We recently described controlled Fab-arm exchange (cFAE) as an easy-to-use method for the generation of therapeutic human IgG1 bispecific antibodies (bsAb). To facilitate the investigation of dual-targeting concepts in immuno-competent mice, we now applied and optimized our method for the generation of murine bsAbs. We show that the optimized combinations of matched point-mutations enabled efficient generation of murine bsAbs for all subclasses studied (mouse IgG1, IgG2a and IgG2b; rat IgG1, IgG2a, IgG2b, and IgG2c). The mutations did not adversely affect the inherent effector functions or pharmacokinetic properties of the corresponding subclasses. Thus, cFAE can be used to efficiently generate (surrogate) mouse or rat bsAbs for pre-clinical evaluation in immuno-competent rodents.
- Published
- 2017
- Full Text
- View/download PDF
22. Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM).
- Author
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Coghlan ML, Maker G, Crighton E, Haile J, Murray DC, White NE, Byard RW, Bellgard MI, Mullaney I, Trengove R, Allcock RJ, Nash C, Hoban C, Jarrett K, Edwards R, Musgrave IF, and Bunce M
- Subjects
- Drug Contamination, Drugs, Chinese Herbal toxicity, Humans, Medicine, Chinese Traditional adverse effects, Metals, Heavy toxicity, Drugs, Chinese Herbal chemistry, Drugs, Chinese Herbal pharmacology, Medicine, Chinese Traditional standards, Metals, Heavy analysis, Pharmacovigilance, Toxicity Tests methods
- Abstract
Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.
- Published
- 2015
- Full Text
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23. Ancient DNA microsatellite analyses of the extinct New Zealand giant moa (Dinornis robustus) identify relatives within a single fossil site.
- Author
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Allentoft ME, Heller R, Holdaway RN, and Bunce M
- Subjects
- Animals, Bone and Bones, DNA, Mitochondrial genetics, Female, Genetics, Population, Haplotypes, Likelihood Functions, New Zealand, Sequence Analysis, DNA, Extinction, Biological, Fossils, Microsatellite Repeats, Palaeognathae genetics
- Abstract
By analysing ancient DNA (aDNA) from 74 (14)C-dated individuals of the extinct South Island giant moa (Dinornis robustus) of New Zealand, we identified four dyads of closely related adult females. Although our total sample included bones from four fossil deposits located within a 10 km radius, these eight individuals had all been excavated from the same locality. Indications of kinship were based on high pairwise genetic relatedness (rXY) in six microsatellite markers genotyped from aDNA, coupled with overlapping radiocarbon ages. The observed rXY values in the four dyads exceeded a conservative cutoff value for potential relatives obtained from simulated data. In three of the four dyads, the kinship was further supported by observing shared and rare mitochondrial haplotypes. Simulations demonstrated that the proportion of observed dyads above the cutoff value was at least 20 times higher than expected in a randomly mating population with temporal sampling, also when introducing population structure in the simulations. We conclude that the results must reflect social structure in the moa population and we discuss the implications for future aDNA research.
- Published
- 2015
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24. Scrapheap challenge: a novel bulk-bone metabarcoding method to investigate ancient DNA in faunal assemblages.
- Author
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Murray DC, Haile J, Dortch J, White NE, Haouchar D, Bellgard MI, Allcock RJ, Prideaux GJ, and Bunce M
- Subjects
- Archaeology methods, Australia, Fossils, Bone and Bones physiology, DNA genetics
- Abstract
Highly fragmented and morphologically indistinct fossil bone is common in archaeological and paleontological deposits but unfortunately it is of little use in compiling faunal assemblages. The development of a cost-effective methodology to taxonomically identify bulk bone is therefore a key challenge. Here, an ancient DNA methodology using high-throughput sequencing is developed to survey and analyse thousands of archaeological bones from southwest Australia. Fossils were collectively ground together depending on which of fifteen stratigraphical layers they were excavated from. By generating fifteen synthetic blends of bulk bone powder, each corresponding to a chronologically distinct layer, samples could be collectively analysed in an efficient manner. A diverse range of taxa, including endemic, extirpated and hitherto unrecorded taxa, dating back to c.46,000 years BP was characterized. The method is a novel, cost-effective use for unidentifiable bone fragments and a powerful molecular tool for surveying fossils that otherwise end up on the taxonomic "scrapheap".
- Published
- 2013
- Full Text
- View/download PDF
25. Ancient human genome sequence of an extinct Palaeo-Eskimo.
- Author
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Rasmussen M, Li Y, Lindgreen S, Pedersen JS, Albrechtsen A, Moltke I, Metspalu M, Metspalu E, Kivisild T, Gupta R, Bertalan M, Nielsen K, Gilbert MT, Wang Y, Raghavan M, Campos PF, Kamp HM, Wilson AS, Gledhill A, Tridico S, Bunce M, Lorenzen ED, Binladen J, Guo X, Zhao J, Zhang X, Zhang H, Li Z, Chen M, Orlando L, Kristiansen K, Bak M, Tommerup N, Bendixen C, Pierre TL, Grønnow B, Meldgaard M, Andreasen C, Fedorova SA, Osipova LP, Higham TF, Ramsey CB, Hansen TV, Nielsen FC, Crawford MH, Brunak S, Sicheritz-Pontén T, Villems R, Nielsen R, Krogh A, Wang J, and Willerslev E
- Subjects
- Emigration and Immigration history, Genetics, Population, Genomics, Genotype, Greenland, Hair, History, Ancient, Humans, Male, Phenotype, Phylogeny, Polymorphism, Single Nucleotide genetics, Sequence Analysis, DNA, Siberia ethnology, Cryopreservation, Extinction, Biological, Genome, Human genetics, Inuit genetics
- Abstract
We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
- Published
- 2010
- Full Text
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26. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960.
- Author
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Worobey M, Gemmel M, Teuwen DE, Haselkorn T, Kunstman K, Bunce M, Muyembe JJ, Kabongo JM, Kalengayi RM, Van Marck E, Gilbert MT, and Wolinsky SM
- Subjects
- Adult, Canada, Democratic Republic of the Congo epidemiology, Female, HIV Infections pathology, HIV-1 classification, History, 20th Century, Humans, Male, Microtomy, Molecular Sequence Data, Paraffin Embedding, Phylogeny, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Evolution, Molecular, Genetic Variation genetics, HIV Infections epidemiology, HIV Infections virology, HIV-1 genetics, HIV-1 isolation & purification
- Abstract
Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Léopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods.
- Published
- 2008
- Full Text
- View/download PDF
27. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA.
- Author
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Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal S, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, and Goulder PJ
- Subjects
- Africa, Southern, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, Epitopes, T-Lymphocyte immunology, Female, Gene Frequency, Gene Products, nef chemistry, HIV-1 genetics, HLA-A Antigens genetics, HLA-A Antigens immunology, HLA-B Antigens genetics, Humans, Infant, Male, Polymorphism, Genetic genetics, Viral Load, nef Gene Products, Human Immunodeficiency Virus, Biological Evolution, HIV Infections immunology, HIV Infections virology, HIV-1 immunology, HIV-1 physiology, HLA-B Antigens immunology
- Abstract
The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design.
- Published
- 2004
- Full Text
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28. Extreme reversed sexual size dimorphism in the extinct New Zealand moa Dinornis.
- Author
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Bunce M, Worthy TH, Ford T, Hoppitt W, Willerslev E, Drummond A, and Cooper A
- Subjects
- Animals, Biological Evolution, Body Weight, Bone and Bones anatomy & histology, DNA, Mitochondrial genetics, Female, Geography, Male, Molecular Sequence Data, New Zealand, Palaeognathae classification, Palaeognathae genetics, Phylogeny, Sex Determination Analysis, Time Factors, Body Constitution, Ecosystem, Fossils, Palaeognathae anatomy & histology, Sex Characteristics
- Abstract
The ratite moa (Aves; Dinornithiformes) were massive graviportal browsers weighing up to 250 kg (ref. 1) that dominated the New Zealand biota until their extinction approximately 500 yr ago. Despite an extensive Quaternary fossil record, moa taxonomy remains problematic and currently 11 species are recognized. Three Dinornis species were found throughout New Zealand and differed markedly in size (1-2 m height at back) and mass (from approximately 34 to 242 kg). Surprisingly, ancient mitochondrial DNA sequences show that the three species were genetically indistinguishable within each island, but formed separate North and South Island clades. Here we show, using the first sex-linked nuclear sequences from an extinct species, that on each island the three morphological forms actually represent just one species, whose size varied markedly according to sex and habitat. The largest females in this example of extreme reversed sexual size dimorphism were about 280% the weight and 150% the height of the largest males, which is unprecedented among birds and terrestrial mammals. The combination of molecular and palaeontological data highlights the difficulties of analysing extinct groups, even those with detailed fossil records.
- Published
- 2003
- Full Text
- View/download PDF
29. Evolution and transmission of stable CTL escape mutations in HIV infection.
- Author
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Goulder PJ, Brander C, Tang Y, Tremblay C, Colbert RA, Addo MM, Rosenberg ES, Nguyen T, Allen R, Trocha A, Altfeld M, He S, Bunce M, Funkhouser R, Pelton SI, Burchett SK, McIntosh K, Korber BT, and Walker BD
- Subjects
- Adult, Child, DNA, Viral, Disease Progression, Epitopes, T-Lymphocyte genetics, Female, HIV Infections genetics, HIV Infections immunology, HIV Infections virology, HIV-1 immunology, HLA-B27 Antigen immunology, Histocompatibility Testing, Humans, Infectious Disease Transmission, Vertical, HIV Infections transmission, HIV-1 genetics, Mutation, T-Lymphocytes, Cytotoxic immunology
- Abstract
Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.
- Published
- 2001
- Full Text
- View/download PDF
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