Incomplete lineage sorting patterns among human, chimpanzee, and orangutan suggest recent orangutan speciation and widespread selection

Abstract

We search the complete orangutan genome for regions where humans are more closely related to orangutans than to chimpanzees due to incomplete lineage sorting (ILS) in the ancestor of human and chimpanzees. The search uses our recently developed coalescent hidden Markov model (HMM) framework. We find ILS present in ∼1% of the genome, and that the ancestral species of human and chimpanzees never experienced a severe population bottleneck. The existence of ILS is validated with simulations, site pattern analysis, and analysis of rare genomic events. The existence of ILS allows us to disentangle the time of isolation of humans and orangutans (the speciation time) from the genetic divergence time, and we find speciation to be as recent as 9-13 million years ago (Mya; contingent on the calibration point). The analyses provide further support for a recent speciation of human and chimpanzee at ∼4 Mya and a diverse ancestor of human and chimpanzee with an effective population size of about 50,000 individuals. Posterior decoding infers ILS for each nucleotide in the genome, and we use this to deduce patterns of selection in the ancestral species. We demonstrate the effect of background selection in the common ancestor of humans and chimpanzees. In agreement with predictions from population genetics, ILS was found to be reduced in exons and gene-dense regions when we control for confounding factors such as GC content and recombination rate. Finally, we find the broad-scale recombination rate to be conserved through the complete ape phylogeny.

Figure 1.

(A) Probability of (in)congruence as a function of difference in speciation time τ. Consider the human–chimpanzee–gorilla triplet. With a speciation time difference of 2 million years (Myr), a generation time of 20 yr, and an effective human–chimpanzee population size of 50,000, we obtain an incongruence probability of 25%. Assuming a speciation time difference of 8 Myr for the human–chimpanzee–orangutan triplet, we obtain a congruence probability of 98.8%. Thus, the coalescent process predicts 1.2% lineage sorting between human, chimpanzee, and orangutan. (B) If the number of generations r between the speciation time of the three species and the speciation time of human and chimpanzee is small compared to the ancestral (effective) population size N of the human–chimpanzee common ancestor, then a gene from human and chimpanzee does not necessarily find common ancestry within the human–chimpanzee common ancestors. Here τ = t/(2Ng), where g is the generation time in years. (C) Average parameter estimates for the global analysis. (D) The mean time estimates for speciation for 21 autosomal chromosomes.

Figure 2.

Inferred (from posterior decoding) versus expected (from simulations) amounts of ILS as a function of the human–chimp ancestral population size.

Figure 3.

(A) The distribution of fragment lengths supporting each of the four states. A geometric distribution (full line) is fitted to the observed distribution. (B) Examples of an alignment supporting the alternative [(H,O),C] genealogy. The top of the figure shows the posterior probability of being in the basic state (HC1) or in each of the three alternative states (HC2, HO, or CO). The bottom of the figure indicates informative sites and singletons.

Figure 4.

Example estimates along chromosome 7, divided into 131 chunks of 1 Mb of alignment. (A) Estimated speciation times for human–chimpanzee (squares) and human–orangutan (diamonds). (B) Estimated effective sizes of the human–chimpanzee ancestral species (squares) and the human–chimpanzee–orangutan ancestral species. (C) Average recombination rate for each chunk based on the deCODE map. (D) The percentage of incomplete lineage sorting estimated from posterior decoding.

Figure 5.

(A) Amount of ILS in introns and exons for each chromosome as a function of chromosome size. (B) ILS as a function of the deCODE recombination rate. (C) ILS as a function of average exon density of each chromosome. (D) ILS as a function of average intron density of each chromosome.