Mobile elements reveal small population size in the ancient ancestors of Homo sapiens

The genealogies of different genetic loci vary in depth. The deeper the genealogy, the greater the chance that it will include a rare event, such as the insertion of a mobile element. Therefore, the genealogy of a region that contains a mobile element is on average older than that of the rest of the genome. In a simple demographic model, the expected time to most recent common ancestor (TMRCA) is doubled if a rare insertion is present. We test this expectation by examining single nucleotide polymorphisms around polymorphic Alu insertions from two completely sequenced human genomes. The estimated TMRCA for regions containing a polymorphic insertion is two times larger than the genomic average (P < <10−30), as predicted. Because genealogies that contain polymorphic mobile elements are old, they are shaped largely by the forces of ancient population history and are insensitive to recent demographic events, such as bottlenecks and expansions. Remarkably, the information in just two human DNA sequences provides substantial information about ancient human population size. By comparing the likelihood of various demographic models, we estimate that the effective population size of human ancestors living before 1.2 million years ago was 18,500, and we can reject all models where the ancient effective population size was larger than 26,000. This result implies an unusually small population for a species spread across the entire Old World, particularly in light of the effective population sizes of chimpanzees (21,000) and gorillas (25,000), which each inhabit only one part of a single continent.

[1]  T. Kunkel,et al.  Mechanism of a genetic glissando: structural biology of indel mutations. , 2006, Trends in biochemical sciences.

[2]  M. Olivier A haplotype map of the human genome , 2003, Nature.

[3]  P. Deininger,et al.  Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. , 2008, Genome research.

[4]  H. Kazazian,et al.  Retrotransposons Revisited: The Restraint and Rehabilitation of Parasites , 2008, Cell.

[5]  M. Batzer,et al.  Mobile DNA elements in primate and human evolution. , 2007, American journal of physical anthropology.

[6]  Wen-Hsiung Li,et al.  Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1. , 2001, Molecular biology and evolution.

[7]  Timothy B. Stockwell,et al.  The Diploid Genome Sequence of an Individual Human , 2007, PLoS biology.

[8]  T. Ohta Mechanisms of molecular evolution. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[9]  N. Takahata,et al.  Selection, convergence, and intragenic recombination in HLA diversity , 2004, Genetica.

[10]  P. Donnelly,et al.  Inferring coalescence times from DNA sequence data. , 1997, Genetics.

[11]  L. Partridge,et al.  Oxford Surveys in Evolutionary Biology , 1991 .

[12]  M. Nachman,et al.  Estimate of the mutation rate per nucleotide in humans. , 2000, Genetics.

[13]  S. Sherry,et al.  Alu evolution in human populations: using the coalescent to estimate effective population size. , 1997, Genetics.

[14]  S T Sherry,et al.  Genetic traces of ancient demography. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Olivier A haplotype map of the human genome. , 2003, Nature.

[16]  F. Tajima Evolutionary relationship of DNA sequences in finite populations. , 1983, Genetics.

[17]  E. Kirkness,et al.  Mobile elements create structural variation: analysis of a complete human genome. , 2009, Genome research.

[18]  Thierry Heidmann,et al.  LINE-mediated retrotransposition of marked Alu sequences , 2003, Nature Genetics.

[19]  M. Lieber,et al.  The Mechanism of Human Nonhomologous DNA End Joining* , 2008, Journal of Biological Chemistry.

[20]  Francesca Chiaromonte,et al.  Scoring Pairwise Genomic Sequence Alignments , 2001, Pacific Symposium on Biocomputing.

[21]  P. Casali,et al.  DNA Lesions and Repair in Immunoglobulin Class Switch Recombination and Somatic Hypermutation , 2005, Annals of the New York Academy of Sciences.

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

[23]  Ziheng Yang,et al.  Estimation of hominoid ancestral population sizes under bayesian coalescent models incorporating mutation rate variation and sequencing errors. , 2008, Molecular biology and evolution.

[24]  Richard Cordaux,et al.  Estimating the retrotransposition rate of human Alu elements. , 2006, Gene.

[25]  R. Hudson,et al.  Single-nucleotide mutation rate increases close to insertions/deletions in eukaryotes , 2008, Nature.

[26]  R. Klein The human career : human biological and cultural origins , 1991 .

[27]  Richard B. Klein,et al.  The human career , 1989 .

[28]  S. Gabriel,et al.  Calibrating a coalescent simulation of human genome sequence variation. , 2005, Genome research.

[29]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[30]  H. Harpending,et al.  Population growth makes waves in the distribution of pairwise genetic differences. , 1992, Molecular biology and evolution.

[31]  Susan Cachel,et al.  The human career: Human biological and cultural origins , 2000 .