Peter Forster

University of Cambridge, Cambridge, England, United Kingdom

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Publications (56)600.59 Total impact

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    ABSTRACT: Men age and die, while cells in their germline are programmed to be immortal. To elucidate how germ cells maintain viable DNA despite increasing parental age, we analysed DNA from 24 097 parents and their children, from Europe, the Middle East and Africa. We chose repetitive microsatellite DNA that mutates (unlike point mutations) only as a result of cellular replication, providing us with a natural ‘cell-cycle counter’. We observe, as expected, that the overall mutation rate for fathers is seven times higher than for mothers. Also as expected, mothers have a low and lifelong constant DNA mutation rate. Surprisingly, however, we discover that (i) teenage fathers already set out from a much higher mutation rate than teenage mothers (potentially equivalent to 77–196 male germline cell divisions by puberty); and (ii) ageing men maintain sperm DNA quality similar to that of teenagers, presumably by using fresh batches of stem cells known as ‘A-dark spermatogonia’.
    Proceedings of the Royal Society B: Biological Sciences 02/2015; 282: 20142898. DOI:10.1098/rspb.2014.2898 · 5.05 Impact Factor
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    Proceedings of the National Academy of Sciences 10/2012; 109(46). DOI:10.1073/pnas.1210326109 · 9.67 Impact Factor
  • Susan M.R. Gurney · Peter Forster · Ursula Just · Ralf Schwanbeck ·
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    ABSTRACT: Phosphatidylinositol-3-kinases (PI3Ks) exert a variety of signaling functions in eukaryotes. We suppressed the PI3K regulatory subunit p85α using a small interfering RNA (Pik3r1 siRNA) and examined the effects on embryoid body (EB) development in hanging drop culture. We observed a 150% increase in the volume of the treated EBs within 24 h, compared to the negative controls. Fluorescence Activated Cell Sorting (FACS) assays showed that this increase in volume is not due to increased cellular proliferation. Instead, the increase in volume appears to be due to reduced cellular aggregation and adherence. This is further shown by our observation that 40% of treated EBs form twin instead of single EBs, and that they have a significantly reduced ability to adhere to culture dishes when plated. A time course over the first 96 h reveals that the impaired adherence is transient and explained by an initial 12-hour delay in EB development. Quantitative PCR expression analysis suggests that the adhesion molecule integrin-β1 (ITGB1) is transiently downregulated by the p85α suppression. In conclusion we found that suppressing p85α leads to a delay in forming compact EBs, accompanied by a transient inability of the EBs to undergo normal cell-cell and cell-substrate adhesion.
    Journal of Cellular Biochemistry 12/2011; 112(12):3573-81. DOI:10.1002/jcb.23285 · 3.26 Impact Factor
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    ABSTRACT: We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.
    Science 09/2011; 334(6052):94-8. DOI:10.1126/science.1211177 · 33.61 Impact Factor
  • Peter Forster · Colin Renfrew ·
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    ABSTRACT: A global picture is emerging of sex-specific transmission of language change in quite different regions and continents.
    Science 09/2011; 333(6048):1390-1. DOI:10.1126/science.1205331 · 33.61 Impact Factor
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    ABSTRACT: Horse mtDNA profiling can be useful in forensic work investigating degraded samples, hair shafts or highly dilute samples. Degraded DNA often does not allow sequencing of fragments longer than 200 nucleotides. In this study we therefore search for the most discriminatory sections within the hypervariable horse mtDNA control region. Among a random sample of 39 horses, 32 different sequences were identified in a stretch of 921 nucleotides. The sequences were assigned to the published mtDNA types A-G, and to a newly labelled minor type H. The random match probability within the analysed samples is 3.61%, and the average pairwise sequence difference is 15 nucleotides. In a "sliding window" analysis of 200-nucleotide sections of the mtDNA control region, we find that the known repetitive central motif divides the mtDNA control region into a highly diverse segment and a markedly less discriminatory segment.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 11/2010; 124(6):617-22. DOI:10.1007/s00414-010-0506-9 · 2.71 Impact Factor
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    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 04/2010; 124(4). DOI:10.1007/s00414-010-0435-7 · 2.71 Impact Factor
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    ABSTRACT: We present allelic data for three known and one new C-tract in the human mitochondrial DNA (mtDNA) control region, and we measure intergenerational mutation rates at such C-tracts. In detail, in a sample of 1,172 mtDNA sequences, we demonstrate the existence of an instability threshold of eight consecutive cytosines, at and above which the phenomenon of length heteroplasmy arises. To determine mutation rates, we draw on mtDNA sequences in up to four generations of 248 pedigrees for families living in high or low-radiation environmental conditions. The high-radiation sample gives the most conservative (fastest) mutation rate likely to be encountered in any forensic context. We find that the C-tract mutation rate is up to 6% per generation, and we observe an excess of cytosine gains over losses. Case studies and guidelines for evaluating mtDNA heteroplasmy are provided.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 11/2009; 124(2):133-42. DOI:10.1007/s00414-009-0385-0 · 2.71 Impact Factor
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    ABSTRACT: After the domestication of animals and crops in the Near East some 11,000 years ago, farming had reached much of central Europe by 7500 years before the present. The extent to which these early European farmers were immigrants or descendants of resident hunter-gatherers who had adopted farming has been widely debated. We compared new mitochondrial DNA (mtDNA) sequences from late European hunter-gatherer skeletons with those from early farmers and from modern Europeans. We find large genetic differences between all three groups that cannot be explained by population continuity alone. Most (82%) of the ancient hunter-gatherers share mtDNA types that are relatively rare in central Europeans today. Together, these analyses provide persuasive evidence that the first farmers were not the descendants of local hunter-gatherers but immigrated into central Europe at the onset of the Neolithic.
    Science 10/2009; 326(5949):137-40. DOI:10.1126/science.1176869 · 33.61 Impact Factor
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    Shuichi Matsumura · Peter Forster ·
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    ABSTRACT: North Greenland Polar Eskimos are the only hunter-gatherer population, to our knowledge, who can offer precise genealogical records spanning several generations. This is the first report from Eskimos on two key parameters in population genetics, namely, generation time (T) and effective population size (Ne). The average mother-daughter and father-son intervals were 27 and 32 years, respectively, roughly similar to the previously published generation times obtained from recent agricultural societies across the world. To gain an insight for the generation time in our distant ancestors, we calculated maternal generation time for two wild chimpanzee populations. We also provide the first comparison among three distinct approaches (genealogy, variance and life table methods) for calculating Ne, which resulted in slightly differing values for the Eskimos. The ratio of the effective to the census population size is estimated as 0.6-0.7 for autosomal and X-chromosomal DNA, 0.7-0.9 for mitochondrial DNA and 0.5 for Y-chromosomal DNA. A simulation of alleles along the genealogy suggested that Y-chromosomal DNA may drift a little faster than mitochondrial DNA in this population, in contrast to agricultural Icelanders. Our values will be useful not only in prehistoric population inference but also in understanding the shaping of our genome today.
    Proceedings of the Royal Society B: Biological Sciences 08/2008; 275(1642):1501-8. DOI:10.1098/rspb.2007.1724 · 5.05 Impact Factor
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    ABSTRACT: Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region.
    Molecular Biology and Evolution 07/2008; 25(6):1209-18. DOI:10.1093/molbev/msn068 · 9.11 Impact Factor
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    ABSTRACT: To estimate Y-chromosomal short tandem repeat (Y-STR) mutation rates, 15 loci (i.e., DYS19, DYS389 I/II, DYS390, and DYS393; DYS437, DYS438, DYS439, and DYS385; DYS391, DYS392, YCA II, and DXYS156) were analyzed in a sample of 1,029 father/son pairs from Westphalia, northwestern Germany. Among 15,435 meiotic allele transfers, 32 mutations were observed; thus, the mutation rate across all 15 Y-STR loci was 2.1 x 10(-3) per locus (95% C.I.: 1.5-3.0 x 10(-3)). With the exception of a three-repeat mutation at DYS385, all remaining mutations were single repeat mutations. Repeat losses were more frequent than gains (20:12), and the mutation rate appeared to increase with age. The Y haplogroups that were detected in the individuals showing a mutation reflect the haplogroup distribution in the Westphalian population. Additionally, the correlation of surnames and haplotypes was tested: Only 49 surnames occurred more than once, and only two men with the same rare surname shared the same haplotype. All other men with identical surnames carried different haplotypes.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 10/2007; 121(5):359-63. DOI:10.1007/s00414-006-0123-9 · 2.71 Impact Factor
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    ABSTRACT: Published and new samples of Aboriginal Australians and Melanesians were analyzed for mtDNA (n=172) and Y variation (n=522), and the resulting profiles were compared with the branches known so far within the global mtDNA and the Y chromosome tree. (i) All Australian lineages are confirmed to fall within the mitochondrial founder branches M and N and the Y chromosomal founders C and F, which are associated with the exodus of modern humans from Africa approximately 50-70,000 years ago. The analysis reveals no evidence for any archaic maternal or paternal lineages in Australians, despite some suggestively robust features in the Australian fossil record, thus weakening the argument for continuity with any earlier Homo erectus populations in Southeast Asia. (ii) The tree of complete mtDNA sequences shows that Aboriginal Australians are most closely related to the autochthonous populations of New Guinea/Melanesia, indicating that prehistoric Australia and New Guinea were occupied initially by one and the same Palaeolithic colonization event approximately 50,000 years ago, in agreement with current archaeological evidence. (iii) The deep mtDNA and Y chromosomal branching patterns between Australia and most other populations around the Indian Ocean point to a considerable isolation after the initial arrival. (iv) We detect only minor secondary gene flow into Australia, and this could have taken place before the land bridge between Australia and New Guinea was submerged approximately 8,000 years ago, thus calling into question that certain significant developments in later Australian prehistory (the emergence of a backed-blade lithic industry, and the linguistic dichotomy) were externally motivated.
    Proceedings of the National Academy of Sciences 06/2007; 104(21):8726-30. DOI:10.1073/pnas.0702928104 · 9.67 Impact Factor
  • Peter Forster · Valentino Romano ·

    Science 05/2007; 316(5821):50-3. DOI:10.1126/science.316.5821.50 · 33.61 Impact Factor
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    ABSTRACT: Island Southeast Asia (ISEA) was first colonized by modern humans at least 45,000 years ago, but the extent to which the modern inhabitants trace their ancestry to the first settlers is a matter of debate. It is widely held, in both archaeology and linguistics, that they are largely descended from a second wave of dispersal, proto-Austronesian-speaking agriculturalists who originated in China and spread to Taiwan approximately 5,500 years ago. From there, they are thought to have dispersed into ISEA approximately 4,000 years ago, assimilating the indigenous populations. Here, we demonstrate that mitochondrial DNA diversity in the region is extremely high and includes a large number of indigenous clades. Only a fraction of these date back to the time of first settlement, and the majority appear to mark dispersals in the late-Pleistocene or early-Holocene epoch most likely triggered by postglacial flooding. There are much closer genetic links to Taiwan than to the mainland, but most of these probably predated the mid-Holocene "Out of Taiwan" event as traditionally envisioned. Only approximately 20% at most of modern mitochondrial DNAs in ISEA could be linked to such an event, suggesting that, if an agriculturalist migration did take place, it was demographically minor, at least with regard to the involvement of women.
    The American Journal of Human Genetics 02/2007; 80(1):29-43. DOI:10.1086/510412 · 10.93 Impact Factor
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    ABSTRACT: The discovery of mitochondrial type N1a in Central European Neolithic skeletons at a high frequency enabled us to answer the question of whether the modern population is maternally descended from the early farmers instead of addressing the traditional question of the origin of early European farmers.
    Science 06/2006; 312(5782). DOI:10.1126/science.1123984 · 33.61 Impact Factor
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    Matthew E Hurles · Bryan C Sykes · Mark A Jobling · Peter Forster ·
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    ABSTRACT: Linguistic and archaeological evidence about the origins of the Malagasy, the indigenous peoples of Madagascar, points to mixed African and Indonesian ancestry. By contrast, genetic evidence about the origins of the Malagasy has hitherto remained partial and imprecise. We defined 26 Y-chromosomal lineages by typing 44 Y-chromosomal polymorphisms in 362 males from four different ethnic groups from Madagascar and 10 potential ancestral populations in Island Southeast Asia and the Pacific. We also compared mitochondrial sequence diversity in the Malagasy with a manually curated database of 19,371 hypervariable segment I sequences, incorporating both published and unpublished data. We could attribute every maternal and paternal lineage found in the Malagasy to a likely geographic origin. Here, we demonstrate approximately equal African and Indonesian contributions to both paternal and maternal Malagasy lineages. The most likely origin of the Asia-derived paternal lineages found in the Malagasy is Borneo. This agrees strikingly with the linguistic evidence that the languages spoken around the Barito River in southern Borneo are the closest extant relatives of Malagasy languages. As a result of their equally balanced admixed ancestry, the Malagasy may represent an ideal population in which to identify loci underlying complex traits of both anthropological and medical interest.
    The American Journal of Human Genetics 06/2005; 76(5):894-901. DOI:10.1086/430051 · 10.93 Impact Factor
  • Peter Forster · Shuichi Matsumura ·

    Science 06/2005; 308(5724):965-6. DOI:10.1126/science.1113261 · 33.61 Impact Factor
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    ABSTRACT: The ancestry of modern Europeans is a subject of debate among geneticists, archaeologists, and anthropologists. A crucial question is the extent to which Europeans are descended from the first European farmers in the Neolithic Age 7500 years ago or from Paleolithic hunter-gatherers who were present in Europe since 40,000 years ago. Here we present an analysis of ancient DNA from early European farmers. We successfully extracted and sequenced intact stretches of maternally inherited mitochondrial DNA (mtDNA) from 24 out of 57 Neolithic skeletons from various locations in Germany, Austria, and Hungary. We found that 25% of the Neolithic farmers had one characteristic mtDNA type and that this type formerly was widespread among Neolithic farmers in Central Europe. Europeans today have a 150-times lower frequency (0.2%) of this mtDNA type, revealing that these first Neolithic farmers did not have a strong genetic influence on modern European female lineages. Our finding lends weight to a proposed Paleolithic ancestry for modern Europeans.
    Science 01/2005; 310:1016//1018. · 33.61 Impact Factor

Publication Stats

6k Citations
600.59 Total Impact Points


  • 2000-2011
    • University of Cambridge
      • • Institute of Continuing Education
      • • McDonald Institute for Archaeological Research
      Cambridge, England, United Kingdom
    • Cancer Research UK Cambridge Institute
      Cambridge, England, United Kingdom
  • 1999-2010
    • University of Münster
      • Institute of Legal Medicine
      Muenster, North Rhine-Westphalia, Germany
  • 2007-2008
    • Anglia Ruskin University
      • Faculty of Science & Technology
      Cambridge, England, United Kingdom
    • Università degli Studi di Palermo
      Palermo, Sicily, Italy
  • 2001
    • University of Pavia
      • Department of Biology and Biotechnology "Lazzaro Spallanzani"
      Ticinum, Lombardy, Italy
  • 1998
    • Friedrich Schiller University Jena
      • Institute of Human Genetics
      Jena, Thuringia, Germany
  • 1996-1998
    • University of Hamburg
      • • Department of Experimental Immunology and Hepatology
      • • Department of Mathematics
      Hamburg, Hamburg, Germany
  • 1997
    • Massey University
      Palmerston North City, Manawatu-Wanganui, New Zealand
  • 1996-1997
    • Heinrich Pette Institute – Leibniz Institute for Experimental Virology
      Hamburg, Hamburg, Germany