Targeted Retrieval and Analysis of Five Neandertal mtDNA Genomes

Economic Ancient DNA Sequencing Analysis of ancient DNA is often limited by the availability of ancient material for sequencing. Briggs et al. (p. 318; see the news story by Pennisi) describe a method of ancient DNA sequence retrieval that greatly reduces shotgun sequencing costs while avoiding the many difficulties associated with direct PCR-based approaches. They generated five complete and one near-complete Neandertal mitochondrial DNA genomes, which would have been economically impossible with a simple shotgun approach. Analysis of these genomes shows that Neandertal populations had a much smaller effective population size than modern humans or great apes. Targeted sequencing improves Neandertal mitochondrial DNA retrieval and reveals low diversity among individuals. Analysis of Neandertal DNA holds great potential for investigating the population history of this group of hominins, but progress has been limited due to the rarity of samples and damaged state of the DNA. We present a method of targeted ancient DNA sequence retrieval that greatly reduces sample destruction and sequencing demands and use this method to reconstruct the complete mitochondrial DNA (mtDNA) genomes of five Neandertals from across their geographic range. We find that mtDNA genetic diversity in Neandertals that lived 38,000 to 70,000 years ago was approximately one-third of that in contemporary modern humans. Together with analyses of mtDNA protein evolution, these data suggest that the long-term effective population size of Neandertals was smaller than that of modern humans and extant great apes.

[1]  X. H. Liu,et al.  Genet. Mol. Res. , 2011 .

[2]  J. Maguire,et al.  Solution Hybrid Selection with Ultra-long Oligonucleotides for Massively Parallel Targeted Sequencing , 2009, Nature Biotechnology.

[3]  Philip L. F. Johnson,et al.  A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing , 2008, Cell.

[4]  Tao Zhang,et al.  Identification of ancient remains through genomic sequencing. , 2008, Genome research.

[5]  R. Mackelprang,et al.  New Tricks with Old Bones , 2008, Science.

[6]  M. Metspalu,et al.  Paleo-Eskimo mtDNA Genome Reveals Matrilineal Discontinuity in Greenland , 2008, Science.

[7]  Aakrosh Ratan,et al.  Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes , 2008, Proceedings of the National Academy of Sciences.

[8]  A. Götherström,et al.  Fishing for ancient DNA. , 2008, Forensic science international. Genetics.

[9]  Alexei J Drummond,et al.  mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory. , 2008, Molecular biology and evolution.

[10]  D. Schneider.  To whom correspondence should be addressed , 2008 .

[11]  Z. Xuan,et al.  Genome-wide in situ exon capture for selective resequencing , 2007, Nature Genetics.

[12]  A. Rambaut,et al.  BEAST: Bayesian evolutionary analysis by sampling trees , 2007, BMC Evolutionary Biology.

[13]  B. Viola,et al.  Neanderthals in central Asia and Siberia , 2007, Nature.

[14]  Philip L. F. Johnson,et al.  Patterns of damage in genomic DNA sequences from a Neandertal , 2007, Proceedings of the National Academy of Sciences.

[15]  M. Beaumont,et al.  Novel high-resolution characterization of ancient DNA reveals C > U-type base modification events as the sole cause of post mortem miscoding lesions , 2007, Nucleic acids research.

[16]  Feng Chen,et al.  Sequencing and Analysis of Neanderthal Genomic DNA , 2006, Science.

[17]  L. Excoffier.  Neandertal Genetic Diversity: A Fresh Look from Old Samples , 2006, Current Biology.

[18]  刘金明,et al.  IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW，Thompson RW，et al//Proc Natl Acad Sci U S A , 2005 .

[19]  Christian N. K. Anderson,et al.  Serial SimCoal: A population genetics model for data from multiple populations and points in time , 2005, Bioinform..

[20]  C. Lalueza-Fox,et al.  Neandertal evolutionary genetics: mitochondrial DNA data from the iberian peninsula. , 2005, Molecular biology and evolution.

[21]  Sergei L. Kosakovsky Pond,et al.  A genetic algorithm approach to detecting lineage-specific variation in selection pressure. , 2005, Molecular biology and evolution.

[22]  V. Doronichev,et al.  ESR dating at Mezmaiskaya Cave, Russia. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[23]  S. Pääbo,et al.  Genetic analyses from ancient DNA. , 2004, Annual review of genetics.

[24]  S. Pääbo,et al.  No Evidence of Neandertal mtDNA Contribution to Early Modern Humans , 2004, PLoS biology.

[25]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[26]  R. McNeill Alexander,et al.  Principles of Animal Locomotion , 2002 .

[27]  S. Pääbo,et al.  The Neandertal type site revisited: Interdisciplinary investigations of skeletal remains from the Neander Valley, Germany , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. von Haeseler,et al.  DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA. , 2001, Nucleic acids research.

[29]  S. Pääbo,et al.  Mitochondrial genome variation and the origin of modern humans , 2000, Nature.

[30]  L. Excoffier,et al.  SIMCOAL: a general coalescent program for the simulation of molecular data in interconnected populations with arbitrary demography. , 2000, The Journal of heredity.

[31]  W. Goodwin,et al.  Molecular analysis of Neanderthal DNA from the northern Caucasus , 2000, Nature.

[32]  D. Turnbull,et al.  Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA , 1999, Nature Genetics.

[33]  J. Ashby.  References and Notes , 1999 .

[34]  S. Vogel,et al.  Life in Moving Fluids , 2020 .

[35]  K. K. Rao.  Statics and kinematics of granular materials , 1995 .

[36]  T. Ohta.  Slightly Deleterious Mutant Substitutions in Evolution , 1973, Nature.

[37]  C. Darwin,et al.  The formation of vegetable mould , 1896 .

[38]  G. Romanes.  The Formation of Vegetable Mould through the Action of Worms, with Observations on their Habits , 1881, Nature.