Great ape genetic diversity and population history

Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria–Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Arcadi Navarro | Thomas Mailund | Jaume Bertranpetit | Hafid Laayouni | Asger Hobolth | Heng Li | Can Alkan | Kay Prüfer | David Comas | Michael Lachmann | Ivo G. Gut | David Reich | Simon Myers | August E. Woerner | Carl Baker | Fereydoun Hormozdiari | Joshua M. Akey | Laurie Stevison | Marc Pybus | Mikkel H. Schierup | Evan E. Eichler | Michael F. Hammer | James C. Mullikin | Kasper Munch | Laura Vives | Carlos D. Bustamante | Ferran Casals | Michael L. Wilson | Anders E. Halager | Krishna R. Veeramah | Anne Pusey | Oliver A. Ryder | Mary Katherine Gonder | Natalia Petit | Marta Gut | Ronald E. Bontrop | Joanna L. Kelley | Mario Ventura | Jeffrey D. Wall | Peter H. Sudmant | Timothy D. O’Connor | Jeffrey M. Kidd | K. Veeramah | M. Hammer | C. Baker | E. Eichler | J. Kelley | M. Malig | P. Sudmant | C. Alkan | R. Wilson | F. Hormozdiari | L. Vives | S. Tishkoff | J. Mullikin | L. Fulton | D. Reich | J. Wall | A. Hobolth | C. Bustamante | A. Andrés | M. Lachmann | J. Kidd | T. Marquès-Bonet | S. Myers | M. Ventura | M. Gut | I. Gut | M. Pybus | D. Comas | J. Akey | Marta Melé | Kay Prüfer | Belén Lorente-Galdos | J. Bertranpetit | A. Navarro | T. Mailund | M. Schierup | O. Ryder | A. Pusey | B. Hahn | R. Bontrop | T. O’Connor | Heng Li | H. Siegismund | K. Munch | F. Casals | M. K. Gonder | G. Santpere | H. Laayouni | Christoph Theunert | A. Cagan | P. Gagneux | N. Petit | E. Lonsdorf | Javier Prado-Martinez | I. Hernando-Herraez | A. Ruiz-Herrera | Marc Dabad | J. Blanc | R. Bergl | C. Hvilsom | Marcos Fernández-Callejo | J. Hernandez-Rodriguez | L. Johnstone | I. Kondova | Tiago Carvalho | Richard K. Wilson | Tomas Marques-Bonet | Maika Malig | Ivanela Kondova | Beatrice H. Hahn | M. Wilson | Pascal Gagneux | Sarah A. Tishkoff | Jessica Hernandez-Rodriguez | Lucinda Fulton | L. Stevison | Christoph Theunert | Irene Hernando-Herraez | D. Twigg | C. Camprubí | T. Abelló | F. Lankester | J. Kiyang | Lidia Agueda-Calpena | Aurora Ruiz-Herrera | Aida M. Andrés | Julie Blanc | Gabriel Santpere | Javier Prado-Martinez | Belen Lorente-Galdos | Alexander Cagan | Laurel Johnstone | Dorina Twigg | Marcos Fernandez-Callejo | Marc Dabad | Cristina Camprubí | Tiago Carvalho | Marta Mele | Teresa Abello | Felix Lankester | John A. Kiyang | Richard A. Bergl | Elizabeth Lonsdorf | Hans Siegismund | Lidia Agueda-Calpena | Christina Hvilsom | Jessica Hernandez-Rodriguez | Teresa Abelló | Carl A. Baker | Laura Vives | Tomàs Marquès-Bonet | R. Wilson | B. Lorente-Galdos | Natalia Petit | Maika Malig

[1]  A. Hobolth,et al.  Genomic Relationships and Speciation Times of Human, Chimpanzee, and Gorilla Inferred from a Coalescent Hidden Markov Model , 2006, PLoS genetics.

[2]  T. Mailund,et al.  Lineage sorting in apes. , 2014, Annual review of genetics.

[3]  Anna Wetterbom,et al.  Genome-wide analysis of chimpanzee genes with premature termination codons , 2009, BMC Genomics.

[4]  Ryan D. Hernandez,et al.  Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data , 2009, PLoS genetics.

[5]  Richard M Myers,et al.  Genomic patterns of homozygosity in worldwide human populations. , 2012, American journal of human genetics.

[6]  Byungkook Lee,et al.  Identification of nine human-specific frameshift mutations by comparative analysis of the human and the chimpanzee genome sequences , 2005, ISMB.

[7]  David H. Alexander,et al.  Fast model-based estimation of ancestry in unrelated individuals. , 2009, Genome research.

[8]  J. Kitzman,et al.  Personalized Copy-Number and Segmental Duplication Maps using Next-Generation Sequencing , 2009, Nature Genetics.

[9]  R. Nielsen,et al.  Distinguishing migration from isolation: a Markov chain Monte Carlo approach. , 2001, Genetics.

[10]  Christian P Robert,et al.  Lack of confidence in approximate Bayesian computation model choice , 2011, Proceedings of the National Academy of Sciences.

[11]  G. Achaz.  Testing for Neutrality in Samples With Sequencing Errors , 2008, Genetics.

[12]  Laurent Excoffier,et al.  Bayesian inference of the demographic history of chimpanzees. , 2010, Molecular biology and evolution.

[13]  Daniel Wegmann,et al.  Bayesian Computation and Model Selection Without Likelihoods , 2010, Genetics.

[14]  N. Risch,et al.  Estimation of individual admixture: Analytical and study design considerations , 2005, Genetic epidemiology.

[15]  R. Nielsen,et al.  POPULATION SIZE CHANGES RESHAPE GENOMIC PATTERNS OF DIVERSITY , 2007, Evolution; international journal of organic evolution.

[16]  Mary Katherine Gonder,et al.  Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations , 2011, Proceedings of the National Academy of Sciences.

[17]  D. Reich,et al.  Can a sex-biased human demography account for the reduced effective population size of chromosome X in non-Africans? , 2010, Molecular biology and evolution.

[18]  M V Olson,et al.  When less is more: gene loss as an engine of evolutionary change. , 1999, American journal of human genetics.

[19]  Jean L. Chang,et al.  Initial sequence of the chimpanzee genome and comparison with the human genome , 2005, Nature.

[20]  Christophe Boesch,et al.  Alarming decline of West African chimpanzees in Côte d'Ivoire , 2008, Current Biology.

[21]  Adrian W. Briggs,et al.  A High-Coverage Genome Sequence from an Archaic Denisovan Individual , 2012, Science.

[22]  Joseph K. Pickrell,et al.  Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data , 2012, PLoS genetics.

[23]  J. J. Moore,et al.  Kin selection, social structure, gene flow, and the evolution of chimpanzees. , 1994, Science.

[24]  P. Sharp,et al.  AIDS as a zoonosis: scientific and public health implications. , 2000, Science.

[25]  H. Innan,et al.  Inferring the Process of Human–Chimpanzee Speciation , 2008 .

[26]  D. Balding,et al.  Approximate Bayesian computation in population genetics. , 2002, Genetics.

[27]  August E. Woerner,et al.  The ratio of human X chromosome to autosome diversity is positively correlated with genetic distance from genes , 2010, Nature Genetics.

[28]  P. Shannon,et al.  Analysis of Genetic Inheritance in a Family Quartet by Whole-Genome Sequencing , 2010, Science.

[29]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[30]  A. Siepel,et al.  Bayesian inference of ancient human demography from individual genome sequences , 2011, Nature Genetics.

[31]  Anders E. Halager,et al.  A New Isolation with Migration Model along Complete Genomes Infers Very Different Divergence Processes among Closely Related Great Ape Species , 2012, PLoS genetics.

[32]  Arcadi Navarro,et al.  A burst of segmental duplications in the genome of the African great ape ancestor , 2009, Nature.

[33]  Igor Rudan,et al.  Runs of homozygosity in European populations. , 2008, American journal of human genetics.

[34]  Albert J. Vilella,et al.  Insights into hominid evolution from the gorilla genome sequence , 2012, Nature.

[35]  F..  THE MUTATION LOAD IN SMALL POPULATIONS , 2022 .

[36]  A. Hobolth,et al.  Estimating Divergence Time and Ancestral Effective Population Size of Bornean and Sumatran Orangutan Subspecies Using a Coalescent Hidden Markov Model , 2011, PLoS genetics.

[37]  H. Hakonarson,et al.  ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data , 2010, Nucleic acids research.

[38]  Saharon Rosset,et al.  A "Copernican" reassessment of the human mitochondrial DNA tree from its root. , 2012, American journal of human genetics.

[39]  M. DePristo,et al.  A framework for variation discovery and genotyping using next-generation DNA sequencing data , 2011, Nature Genetics.

[40]  J. Hey.  The divergence of chimpanzee species and subspecies as revealed in multipopulation isolation-with-migration analyses. , 2010, Molecular biology and evolution.

[41]  L. Wain,et al.  Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1 , 2006, Science.

[42]  Sergey Koren,et al.  The bonobo genome compared with the chimpanzee and human genomes , 2012, Nature.

[43]  D. Reich,et al.  Analysis of Chimpanzee History Based on Genome Sequence Alignments , 2008, PLoS genetics.

[44]  A. Futschik,et al.  Approximate Bayesian computation for modular inference problems with many parameters: the example of migration rates , 2013, Molecular ecology.

[45]  J. Wakeley,et al.  Estimating ancestral population parameters. , 1997, Genetics.

[46]  J. Wakeley,et al.  Distinguishing migration from isolation using the variance of pairwise differences. , 1996, Theoretical population biology.

[47]  Anders Eriksson,et al.  Effect of ancient population structure on the degree of polymorphism shared between modern human populations and ancient hominins , 2012, Proceedings of the National Academy of Sciences.

[48]  D. Reich,et al.  Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations , 2009, PLoS genetics.

[49]  M. Feldman,et al.  Population growth of human Y chromosomes: a study of Y chromosome microsatellites. , 1999, Molecular biology and evolution.

[50]  Laurent Excoffier,et al.  ABCtoolbox: a versatile toolkit for approximate Bayesian computations , 2010, BMC Bioinformatics.

[51]  References , 1971 .

[52]  Ziheng Yang,et al.  Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci. , 2003, Genetics.

[53]  Albert J. Vilella,et al.  Comparative and demographic analysis of orang-utan genomes , 2011, Nature.

[54]  G. Coop,et al.  An evolutionary view of human recombination , 2007, Nature Reviews Genetics.

[55]  Philip L. F. Johnson,et al.  The complete genome sequence of a Neanderthal from the Altai Mountains , 2013 .

[56]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[57]  S. Pääbo,et al.  The complex evolutionary history of gorillas: insights from genomic data. , 2006, Molecular biology and evolution.

[58]  Ryan D. Hernandez,et al.  A Fine-Scale Chimpanzee Genetic Map from Population Sequencing , 2012, Science.

[59]  R. Durbin,et al.  Inference of human population history from individual whole-genome sequences. , 2011, Nature.

[60]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[61]  Kenneth Lange,et al.  Enhancements to the ADMIXTURE algorithm for individual ancestry estimation , 2011, BMC Bioinformatics.

[62]  B. Hahn,et al.  Evolutionary history of chimpanzees inferred from complete mitochondrial genomes. , 2011, Molecular biology and evolution.

[63]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[64]  Zhaoxia Yu,et al.  Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies. , 2009, American journal of human genetics.

[65]  S. Bergmann,et al.  The evolution of gene expression levels in mammalian organs , 2011, Nature.

[66]  Jianzhi Zhang,et al.  Gene Losses during Human Origins , 2006, PLoS biology.

[67]  K. Katoh,et al.  MAFFT version 5: improvement in accuracy of multiple sequence alignment , 2005, Nucleic acids research.

[68]  Josyf Mychaleckyj,et al.  Robust relationship inference in genome-wide association studies , 2010, Bioinform..

[69]  J. Mullikin,et al.  SSAHA: a fast search method for large DNA databases. , 2001, Genome research.

[70]  Süleyman Cenk Sahinalp,et al.  Combinatorial Algorithms for Structural Variation Detection in High Throughput Sequenced Genomes , 2009, RECOMB.

[71]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[72]  S. Pääbo,et al.  Bonobos Fall within the Genomic Variation of Chimpanzees , 2011, PloS one.

[73]  August E. Woerner,et al.  Extreme selective sweeps independently targeted the X chromosomes of the great apes , 2015, Proceedings of the National Academy of Sciences.

[74]  Nilgun Donmez,et al.  Hapsembler: An Assembler for Highly Polymorphic Genomes , 2011, RECOMB.

[75]  L. Excoffier,et al.  Efficient Approximate Bayesian Computation Coupled With Markov Chain Monte Carlo Without Likelihood , 2009, Genetics.

[76]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

[77]  Ryan D. Hernandez,et al.  Natural selection on protein-coding genes in the human genome , 2005, Nature.

[78]  Chris S. Duvall,et al.  Recent decline in suitable environmental conditions for African great apes , 2012 .

[79]  M. K. Gonder,et al.  A new west African chimpanzee subspecies? , 1997, Nature.

[80]  Jody Hey,et al.  Divergence population genetics of chimpanzees. , 2004, Molecular biology and evolution.

[81]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[82]  Byungkook Lee,et al.  Human-specific nonsense mutations identified by genome sequence comparisons , 2006, Human Genetics.

[83]  Arcadi Navarro,et al.  Gorilla genome structural variation reveals evolutionary parallelisms with chimpanzee. , 2011, Genome research.

[84]  N. Rosenberg,et al.  Discordance of Species Trees with Their Most Likely Gene Trees , 2006, PLoS genetics.

[85]  Richard R. Hudson,et al.  Generating samples under a Wright-Fisher neutral model of genetic variation , 2002, Bioinform..

[86]  Philip L. F. Johnson,et al.  A Draft Sequence of the Neandertal Genome , 2010, Science.

[87]  August E. Woerner,et al.  An early divergence of KhoeSan ancestors from those of other modern humans is supported by an ABC-based analysis of autosomal resequencing data. , 2012, Molecular biology and evolution.

[88]  D. Reich,et al.  Population Structure and Eigenanalysis , 2006, PLoS genetics.

[89]  M. Przeworski,et al.  A new approach to estimate parameters of speciation models with application to apes. , 2007, Genome research.

[90]  L. Chemnick,et al.  The cryptic genetic structure of the North American captive gorilla population , 2010, Conservation Genetics.

[91]  Life Technologies,et al.  A map of human genome variation from population-scale sequencing , 2011 .

[92]  L. Excoffier,et al.  Statistical evaluation of alternative models of human evolution , 2007, Proceedings of the National Academy of Sciences.

[93]  P. Donnelly,et al.  Genomic Tools for Evolution and Conservation in the Chimpanzee: Pan troglodytes ellioti Is a Genetically Distinct Population , 2012, PLoS genetics.

[94]  Ryan D. Hernandez,et al.  Classic Selective Sweeps Were Rare in Recent Human Evolution , 2011, Science.

[95]  Jun Wang,et al.  Extensive X-linked adaptive evolution in central chimpanzees , 2012, Proceedings of the National Academy of Sciences.

[96]  David Reich,et al.  Testing for ancient admixture between closely related populations. , 2011, Molecular biology and evolution.

[97]  R. Durbin,et al.  Revising the human mutation rate: implications for understanding human evolution , 2012, Nature Reviews Genetics.

[98]  Ajit Varki,et al.  Sequencing the chimpanzee genome: insights into human evolution and disease , 2003, Nature Reviews Genetics.

[99]  Sergio Lukić,et al.  Demographic Inference Using Spectral Methods on SNP Data, with an Analysis of the Human Out-of-Africa Expansion , 2012, Genetics.