Testing for Archaic Hominin Admixture on the X Chromosome: Model Likelihoods for the Modern Human RRM2P4 Region From Summaries of Genealogical Topology Under the Structured Coalescent

Abstract

A 2.4-kb stretch within the RRM2P4 region of the X chromosome, previously sequenced in a sample of 41 globally distributed humans, displayed both an ancient time to the most recent common ancestor (e.g., a TMRCA of $2 million years) and a basal clade composed entirely of Asian sequences. This pattern was interpreted to reflect a history of introgressive hybridization from archaic hominins (most likely Asian Homo erectus) into the anatomically modern human genome. Here, we address this hypothesis by resequencing the 2.4-kb RRM2P4 region in 131 African and 122 non-African individuals and by extending the length of sequence in a window of 16.5 kb encompassing the RRM2P4 pseudogene in a subset of 90 individuals. We find that both the ancient TMRCA and the skew in non-African representation in one of the basal clades are essentially limited to the central 2.4-kb region. We define a new summary statistic called the minimum clade proportion (p mc ), which quantifies the proportion of individuals from a specified geographic region in each of the two basal clades of a binary gene tree, and then employ coalescent simulations to assess the likelihood of the observed central RRM2P4 genealogy under two alternative views of human evolutionary history: recent African replacement (RAR) and archaic admixture (AA). A molecular-clock-based TMRCA estimate of 2.33 million years is a statistical outlier under the RAR model; however, the large variance associated with this estimate makes it difficult to distinguish the predictions of the human origins models tested here. The p mc summary statistic, which has improved power with larger samples of chromosomes, yields values that are significantly unlikely under the RAR model and fit expectations better under a range of archaic admixture scenarios.

The Microcephalin Ancestral Allele in a Neanderthal Individual

“…The deep split in the gene genealogy described for MCPH1 [4] has been observed at other loci as well, including pyruvate dehydrogenase alpha 1 [27], Dystrophin [28], coagulation factor FVII [29], and two regions of chromosome X [30], [31]. These high levels of haplotype divergence, caused by several nucleotide substitutions between two major branches of the gene tree, have been interpreted as evidence for introgression followed by positive selection [32], but in fact that is not the only plausible explanation.…”

Genetic evidence for archaic admixture in Africa

“…As proof of principle that an indirect approach can be useful, we reexamined the RRM2P4 pseudogene on the X chromosome. Using a similar approximate-likelihood methodology, it was previously posited that a divergent allele at the pseudogene introgressed from an archaic taxon in Asia (27,28). We compared human and Neandertal RRM2P4 sequences and found that the three derived sites that define the non-African basal lineage are shared with Neandertal (Fig.…”

Bias in estimators of archaic admixture

“…Some rely on information in the site frequency spectrum (Eswaran et al, 2005;Yang et al, 2012). Others are based on linkage disequilibrium (Wall, 2000;Wall et al, 2009;Wall and Hammer, 2006;Plagnol and Wall, 2006;Moorjani et al, 2011;Hammer et al, 2011;Abi-Rached et al, 2011;Evans et al, 2005;Mendez et al, 2012;Cox et al, 2008).…”