Limits...
Inferring demographic history from a spectrum of shared haplotype lengths.

Harris K, Nielsen R - PLoS Genet. (2013)

Bottom Line: Using the same technique, we analyze deeply sequenced trio parents from the 1000 Genomes project.The data show evidence of extensive gene flow between Africa and Europe after the time of divergence as well as substructure and gene flow among ancestral hominids.In particular, we infer that recent African-European gene flow and ancient ghost admixture into Europe are both necessary to explain the spectrum of IBS sharing in the trios, rejecting simpler models that contain less population structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, University of California Berkeley, Berkeley, CA, USA. kharris@math.berkeley.edu

ABSTRACT
There has been much recent excitement about the use of genetics to elucidate ancestral history and demography. Whole genome data from humans and other species are revealing complex stories of divergence and admixture that were left undiscovered by previous smaller data sets. A central challenge is to estimate the timing of past admixture and divergence events, for example the time at which Neanderthals exchanged genetic material with humans and the time at which modern humans left Africa. Here, we present a method for using sequence data to jointly estimate the timing and magnitude of past admixture events, along with population divergence times and changes in effective population size. We infer demography from a collection of pairwise sequence alignments by summarizing their length distribution of tracts of identity by state (IBS) and maximizing an analytic composite likelihood derived from a Markovian coalescent approximation. Recent gene flow between populations leaves behind long tracts of identity by descent (IBD), and these tracts give our method power by influencing the distribution of shared IBS tracts. In simulated data, we accurately infer the timing and strength of admixture events, population size changes, and divergence times over a variety of ancient and recent time scales. Using the same technique, we analyze deeply sequenced trio parents from the 1000 Genomes project. The data show evidence of extensive gene flow between Africa and Europe after the time of divergence as well as substructure and gene flow among ancestral hominids. In particular, we infer that recent African-European gene flow and ancient ghost admixture into Europe are both necessary to explain the spectrum of IBS sharing in the trios, rejecting simpler models that contain less population structure.

Show MeSH
Mutation and recombination rates within -base IBS tracts.Figure 6A shows that there is no length class of IBS tracts with a significantly higher or lower mutation rate than the genome-wide average (recombination rates are taken from the deCODE genetic map [53]). In contrast, Figure 6B shows that IBS tracts shorter than 100 base pairs occur in regions with higher rates of human-chimp differences than the genomewide average. These plots were made using IBS tracts shared between Europeans and Africans, but the results are similar for IBS sharing within each of the populations.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3675002&req=5

pgen-1003521-g006: Mutation and recombination rates within -base IBS tracts.Figure 6A shows that there is no length class of IBS tracts with a significantly higher or lower mutation rate than the genome-wide average (recombination rates are taken from the deCODE genetic map [53]). In contrast, Figure 6B shows that IBS tracts shorter than 100 base pairs occur in regions with higher rates of human-chimp differences than the genomewide average. These plots were made using IBS tracts shared between Europeans and Africans, but the results are similar for IBS sharing within each of the populations.

Mentions: To gauge the effects of recombination rate variation, we used the DECODE genetic map [53] to calculate the average recombination rate across all sites that are part of -base IBS tracts. The results, plotted in Figure 6A, show no significant difference between the average recombination rate within long IBS tracts versus short ones. If recombination hotspots significantly reduced the frequency of long IBS tracts compared to what we would expect under the assumption of constant recombination rate, then the longest observed IBS tracts should span regions of lower-than-average recombination rate; conversely, if recombination hotspots significantly increased the frequency of short IBS tracts, we would expect to see short tracts concentrated in regions of higher-than-average recombination rate. We observed neither of these patterns and therefore made no special effort to correct for recombination rate variation. Li and Durbin made a similar decision with regard to the PSMC, which can accurately infer past population sizes from data with simulated recombination hotspots.


Inferring demographic history from a spectrum of shared haplotype lengths.

Harris K, Nielsen R - PLoS Genet. (2013)

Mutation and recombination rates within -base IBS tracts.Figure 6A shows that there is no length class of IBS tracts with a significantly higher or lower mutation rate than the genome-wide average (recombination rates are taken from the deCODE genetic map [53]). In contrast, Figure 6B shows that IBS tracts shorter than 100 base pairs occur in regions with higher rates of human-chimp differences than the genomewide average. These plots were made using IBS tracts shared between Europeans and Africans, but the results are similar for IBS sharing within each of the populations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675002&req=5

pgen-1003521-g006: Mutation and recombination rates within -base IBS tracts.Figure 6A shows that there is no length class of IBS tracts with a significantly higher or lower mutation rate than the genome-wide average (recombination rates are taken from the deCODE genetic map [53]). In contrast, Figure 6B shows that IBS tracts shorter than 100 base pairs occur in regions with higher rates of human-chimp differences than the genomewide average. These plots were made using IBS tracts shared between Europeans and Africans, but the results are similar for IBS sharing within each of the populations.
Mentions: To gauge the effects of recombination rate variation, we used the DECODE genetic map [53] to calculate the average recombination rate across all sites that are part of -base IBS tracts. The results, plotted in Figure 6A, show no significant difference between the average recombination rate within long IBS tracts versus short ones. If recombination hotspots significantly reduced the frequency of long IBS tracts compared to what we would expect under the assumption of constant recombination rate, then the longest observed IBS tracts should span regions of lower-than-average recombination rate; conversely, if recombination hotspots significantly increased the frequency of short IBS tracts, we would expect to see short tracts concentrated in regions of higher-than-average recombination rate. We observed neither of these patterns and therefore made no special effort to correct for recombination rate variation. Li and Durbin made a similar decision with regard to the PSMC, which can accurately infer past population sizes from data with simulated recombination hotspots.

Bottom Line: Using the same technique, we analyze deeply sequenced trio parents from the 1000 Genomes project.The data show evidence of extensive gene flow between Africa and Europe after the time of divergence as well as substructure and gene flow among ancestral hominids.In particular, we infer that recent African-European gene flow and ancient ghost admixture into Europe are both necessary to explain the spectrum of IBS sharing in the trios, rejecting simpler models that contain less population structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, University of California Berkeley, Berkeley, CA, USA. kharris@math.berkeley.edu

ABSTRACT
There has been much recent excitement about the use of genetics to elucidate ancestral history and demography. Whole genome data from humans and other species are revealing complex stories of divergence and admixture that were left undiscovered by previous smaller data sets. A central challenge is to estimate the timing of past admixture and divergence events, for example the time at which Neanderthals exchanged genetic material with humans and the time at which modern humans left Africa. Here, we present a method for using sequence data to jointly estimate the timing and magnitude of past admixture events, along with population divergence times and changes in effective population size. We infer demography from a collection of pairwise sequence alignments by summarizing their length distribution of tracts of identity by state (IBS) and maximizing an analytic composite likelihood derived from a Markovian coalescent approximation. Recent gene flow between populations leaves behind long tracts of identity by descent (IBD), and these tracts give our method power by influencing the distribution of shared IBS tracts. In simulated data, we accurately infer the timing and strength of admixture events, population size changes, and divergence times over a variety of ancient and recent time scales. Using the same technique, we analyze deeply sequenced trio parents from the 1000 Genomes project. The data show evidence of extensive gene flow between Africa and Europe after the time of divergence as well as substructure and gene flow among ancestral hominids. In particular, we infer that recent African-European gene flow and ancient ghost admixture into Europe are both necessary to explain the spectrum of IBS sharing in the trios, rejecting simpler models that contain less population structure.

Show MeSH