Estimating variable effective population sizes from multiple genomes: a sequentially markov conditional sampling distribution approach

Genetics. 2013 Jul;194(3):647-62. doi: 10.1534/genetics.112.149096. Epub 2013 Apr 22.


Throughout history, the population size of modern humans has varied considerably due to changes in environment, culture, and technology. More accurate estimates of population size changes, and when they occurred, should provide a clearer picture of human colonization history and help remove confounding effects from natural selection inference. Demography influences the pattern of genetic variation in a population, and thus genomic data of multiple individuals sampled from one or more present-day populations contain valuable information about the past demographic history. Recently, Li and Durbin developed a coalescent-based hidden Markov model, called the pairwise sequentially Markovian coalescent (PSMC), for a pair of chromosomes (or one diploid individual) to estimate past population sizes. This is an efficient, useful approach, but its accuracy in the very recent past is hampered by the fact that, because of the small sample size, only few coalescence events occur in that period. Multiple genomes from the same population contain more information about the recent past, but are also more computationally challenging to study jointly in a coalescent framework. Here, we present a new coalescent-based method that can efficiently infer population size changes from multiple genomes, providing access to a new store of information about the recent past. Our work generalizes the recently developed sequentially Markov conditional sampling distribution framework, which provides an accurate approximation of the probability of observing a newly sampled haplotype given a set of previously sampled haplotypes. Simulation results demonstrate that we can accurately reconstruct the true population histories, with a significant improvement over the PSMC in the recent past. We apply our method, called diCal, to the genomes of multiple human individuals of European and African ancestry to obtain a detailed population size change history during recent times.

Keywords: hidden Markov model (HMM); population size; recombination; sequentially Markov coalescent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Chromosomes / genetics
  • Computer Simulation
  • Genetic Variation*
  • Genetics, Population
  • Genome, Human
  • Haplotypes / genetics*
  • Humans
  • Markov Chains*
  • Models, Genetic*
  • Population Density
  • Probability
  • Selection, Genetic*