Detection of human adaptation during the past 2000 years

Identifying genes under recent selection Evolutionary analyses aim to identify recent genetic changes that are likely to have been subject to selection. Field et al. present a method to identify such changes, the singleton density score, which they applied to over 3000 human genomes. Over the past ∼100 generations (2000 to 3000 years), Europeans are likely to have experienced selection for genetic variants, including those that affect skin and hair pigmentation, as well as height. Science, this issue p. 760 The singleton density score identifies evidence of recent selection in Europeans. Detection of recent natural selection is a challenging problem in population genetics. Here we introduce the singleton density score (SDS), a method to infer very recent changes in allele frequencies from contemporary genome sequences. Applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past ~2000 to 3000 years. We see strong signals of selection at lactase and the major histocompatibility complex, and in favor of blond hair and blue eyes. For polygenic adaptation, we find that recent selection for increased height has driven allele frequency shifts across most of the genome. Moreover, we identify shifts associated with other complex traits, suggesting that polygenic adaptation has played a pervasive role in shaping genotypic and phenotypic variation in modern humans.

[1]  Anand Bhaskar,et al.  Efficient inference of population size histories and locus-specific mutation rates from large-sample genomic variation data , 2014, bioRxiv.

[2]  Mark D Shriver,et al.  The timing of pigmentation lightening in Europeans. , 2013, Molecular biology and evolution.

[3]  Soumya Raychaudhuri,et al.  Interrogating the major histocompatibility complex with high-throughput genomics. , 2012, Human molecular genetics.

[4]  Anders Albrechtsen,et al.  Greenlandic Inuit show genetic signatures of diet and climate adaptation , 2015, Science.

[5]  Adam Powell,et al.  The Origins of Lactase Persistence in Europe , 2009, PLoS Comput. Biol..

[6]  J. Hermisson,et al.  Soft Sweeps , 2005, Genetics.

[7]  G. Coop,et al.  A Coalescent Model for a Sweep of a Unique Standing Variant , 2015, Genetics.

[8]  Xiaofeng Zhu,et al.  Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection. , 2011, American journal of human genetics.

[9]  Asan,et al.  Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude , 2010, Science.

[10]  Jerome Kelleher,et al.  Efficient Coalescent Simulation and Genealogical Analysis for Large Sample Sizes , 2015, bioRxiv.

[11]  J. Toppari,et al.  The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. , 2003, Endocrine reviews.

[12]  Adam Powell,et al.  Evolution of lactase persistence: an example of human niche construction , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[13]  Valerie A. I. Natale,et al.  Worldwide variation in human growth and the World Health Organization growth standards: a systematic review , 2014, BMJ Open.

[14]  F. Maytag Evolution , 1996, Arch. Mus. Informatics.

[15]  Alex A. Pollen,et al.  cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans , 2007, Cell.

[16]  Jacob A. Tennessen,et al.  Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes , 2012, Science.

[17]  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 .

[18]  Tom R. Gaunt,et al.  The UK10K project identifies rare variants in health and disease , 2016 .

[19]  Kelley Harris Evidence for recent, population-specific evolution of the human mutation rate , 2015, Proceedings of the National Academy of Sciences.

[20]  Joseph K. Pickrell,et al.  The Role of Geography in Human Adaptation , 2009, PLoS genetics.

[21]  Matthew Stephens,et al.  False discovery rates: a new deal , 2016, bioRxiv.

[22]  Peggy Hall,et al.  The NHGRI GWAS Catalog, a curated resource of SNP-trait associations , 2013, Nucleic Acids Res..

[23]  Eric S. Lander,et al.  Identifying Recent Adaptations in Large-Scale Genomic Data , 2013, Cell.

[24]  Marek Kimmel,et al.  simuPOP: a forward-time population genetics simulation environment , 2005, Bioinform..

[25]  P. Visscher,et al.  Population genetic differentiation of height and body mass index across Europe , 2015, Nature Genetics.

[26]  Olga Karapanou,et al.  Determinants of menarche , 2010, Reproductive biology and endocrinology : RB&E.

[27]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[28]  John Maynard Smith,et al.  The hitch-hiking effect of a favourable gene. , 1974, Genetical research.

[29]  J. Murabito,et al.  Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. , 2014, Human molecular genetics.

[30]  Pardis C Sabeti,et al.  Positive Natural Selection in the Human Lineage , 2006, Science.

[31]  Mark George Thomas,et al.  Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y , 2014, Proceedings of the National Academy of Sciences.

[32]  Mathias Currat,et al.  Impact of Selection and Demography on the Diffusion of Lactase Persistence , 2009, PloS one.

[33]  Erik Meijer,et al.  Delete-m Jackknife for Unequal m , 1999, Stat. Comput..

[34]  Carlos D Bustamante,et al.  Localizing Recent Adaptive Evolution in the Human Genome , 2007, PLoS genetics.

[35]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[36]  E. Parra,et al.  Human pigmentation variation: evolution, genetic basis, and implications for public health. , 2007, American journal of physical anthropology.

[37]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[38]  Sharon R Grossman,et al.  Detecting natural selection in genomic data. , 2013, Annual review of genetics.

[39]  Pardis C Sabeti,et al.  Genetic signatures of strong recent positive selection at the lactase gene. , 2004, American journal of human genetics.

[40]  Philippe Froguel,et al.  Direct estimates of natural selection in Iberia indicate calcium absorption was not the only driver of lactase persistence in Europe. , 2014, Molecular biology and evolution.

[41]  B. Charlesworth,et al.  The effect of deleterious mutations on neutral molecular variation. , 1993, Genetics.

[42]  Claudio J. Verzilli,et al.  An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People , 2012, Science.

[43]  H. Künsch The Jackknife and the Bootstrap for General Stationary Observations , 1989 .

[44]  G. Coop,et al.  THE SIGNATURE OF POSITIVE SELECTION ON STANDING GENETIC VARIATION , 2005, Evolution; international journal of organic evolution.

[45]  Zachary A. Szpiech,et al.  selscan: An Efficient Multithreaded Program to Perform EHH-Based Scans for Positive Selection , 2014, Molecular biology and evolution.

[46]  M. P. Concas,et al.  Height-reducing variants and selection for short stature in Sardinia , 2015, Nature Genetics.

[47]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[48]  Peter Donnelly,et al.  Multiple Instances of Ancient Balancing Selection Shared Between Humans and Chimpanzees , 2013, Science.

[49]  Kenny Q. Ye,et al.  An integrated map of genetic variation from 1,092 human genomes , 2012, Nature.

[50]  P. Green,et al.  Widespread Genomic Signatures of Natural Selection in Hominid Evolution , 2009, PLoS genetics.

[51]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[52]  Pardis C Sabeti,et al.  Detecting recent positive selection in the human genome from haplotype structure , 2002, Nature.

[53]  B. Pitt Psychopharmacology , 1968, Mental Health.

[54]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

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

[56]  Joseph K. Pickrell,et al.  The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation , 2010, Current Biology.

[57]  J. Klein,et al.  The molecular descent of the major histocompatibility complex. , 1993, Annual review of immunology.

[58]  C. Langefeld,et al.  Genes Associated with SLE Are Targets of Recent Positive Selection , 2014, Autoimmune diseases.

[59]  E. Demerath,et al.  Meta-analysis of genome-wide association data identifies two loci influencing age at menarche , 2009, Nature Genetics.

[60]  Sravanti L. Sanivarapu Emotion , 2020, Indian journal of psychiatry.

[61]  Ryan D. Hernandez,et al.  Population Genetics of Rare Variants and Complex Diseases , 2013, Human Heredity.

[62]  L. Christophorou Science , 2018, Emerging Dynamics: Science, Energy, Society and Values.

[63]  M. Daly,et al.  An Atlas of Genetic Correlations across Human Diseases and Traits , 2015, Nature Genetics.

[64]  Ross M. Fraser,et al.  Defining the role of common variation in the genomic and biological architecture of adult human height , 2014, Nature Genetics.

[65]  D. Schluter,et al.  Adaptation from standing genetic variation. , 2008, Trends in ecology & evolution.

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

[67]  Joseph K. Pickrell,et al.  Signals of recent positive selection in a worldwide sample of human populations. , 2009, Genome research.

[68]  Cameron D. Palmer,et al.  Evidence of widespread selection on standing variation in Europe at height-associated SNPs , 2012, Nature Genetics.

[69]  J. Akey,et al.  Selection and adaptation in the human genome. , 2013, Annual review of genomics and human genetics.

[70]  G. Coop,et al.  A Population Genetic Signal of Polygenic Adaptation , 2013, PLoS genetics.

[71]  Allan Bäck Parts of Animals , 2014 .

[72]  Carlos Bustamante,et al.  Genomic scans for selective sweeps using SNP data. , 2005, Genome research.

[73]  A. Navarro,et al.  Signatures of Positive Selection in Genes Associated with Human Skin Pigmentation as Revealed from Analyses of Single Nucleotide Polymorphisms , 2007, Annals of human genetics.

[74]  Keith C. Cheng,et al.  SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans , 2005, Science.

[75]  Gil McVean,et al.  Demography and the Age of Rare Variants , 2014, PLoS genetics.

[76]  P. Moorjani,et al.  Human Germline Mutation and the Erratic Evolutionary Clock , 2016, bioRxiv.

[77]  Hideki Innan,et al.  mbs: modifying Hudson's ms software to generate samples of DNA sequences with a biallelic site under selection , 2009, BMC Bioinformatics.

[78]  Joseph Lachance,et al.  Population Genomics of Human Adaptation. , 2013, Annual review of ecology, evolution, and systematics.

[79]  A. Auton,et al.  A direct multi-generational estimate of the human mutation rate from autozygous segments seen in thousands of parentally related individuals , 2016, bioRxiv.

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

[81]  Gregory Ewing,et al.  MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus , 2010, Bioinform..

[82]  N. Wray,et al.  Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance components analysis , 2015, Nature Genetics.

[83]  Mark D Shriver,et al.  The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs , 2004, Human Genomics.

[84]  Ewald Hecker Die Physiologie und Psychologie des Lachens und des Komischen. , 2015 .

[85]  Snæbjörn Pálsson,et al.  Genetic determinants of hair, eye and skin pigmentation in Europeans , 2007, Nature Genetics.

[86]  D. Reich,et al.  Genome-wide patterns of selection in 230 ancient Eurasians , 2015, Nature.

[87]  R. Gibbs,et al.  Neutral genomic regions refine models of recent rapid human population growth , 2013, Proceedings of the National Academy of Sciences.

[88]  J. Pritchard,et al.  A Map of Recent Positive Selection in the Human Genome , 2006, PLoS biology.