The history of great apes

Nature (2013) doi:10.1038/nature12228

Great ape genetic diversity and population history

Javier Prado-Martinez et al.

Most great ape genetic variation remains uncharacterized1, 2; however, its study is critical for understanding population history3, 4, 5, 6, recombination7, selection8 and susceptibility to disease9, 10. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria–Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Link

Genetic variation in gorillas quantified (Scally et al. 2013)

The allele frequency spectrum (Figure 3) from the paper is shown on the left. From the paper:

Figure 3 shows the resulting mean conditional AFS for nine western lowland gorillas (excluding the three lowest-coverage samples as above), and comparable samples from three human populations whose ancestry derives from Africa, Asia and Europe [22]. In a population whose effective size has remained constant, the theoretical expectation for such a conditional AFS is a straight line of constant negative slope [23], shown by the dashed line in Figure 3. Compared to this, western lowland gorillas show a deficit of rare alleles, consistent with their having undergone genetic drift due to a bottleneck or other reduction in effective population size during their demographic history. The similar signal in non-African human populations has been attributed to population contraction associated with the out-of-Africa event [24]. By contrast to the gorillas and the non-African humans, the African YRI population in Figure 3 shows an excess of rare alleles, consistent with population expansion and again similar to the signal seen in other African human data [24]. 

A population bottleneck culls rare alleles, and thus leads to a "dip" in the AFS on the left. An allele that occurs at, say, 10% frequency in a very small population is more likely to go extinct "by accident" than one which occurs at exactly the same frequency in a large population. You can think of this by taking the two extreme cases:

1. if an allele exists in exactly one physical copy (i.e., 1 copy in 5 diploid individuals = 10% frequency), then its bearer must survive, must reproduce, and the allele must be inherited by one offspring in order for it survive.
2. if the population has infinite size, then 10% frequency is still = infinite number of physical copies, hence the allele will survive no matter what [unless it always kills its unlucky bearer, but then how did it end up at 10% frequency in the first place?]

On the other hand, low-frequency alleles become more prevalent when the population expands in the recent past, because there is an ever growing number of bodies, an ever growing number of mutated alleles, but not enough time for these new alleles to grow in frequency.

A different mechanism whereby low-frequency alleles appear in excess in a population is admixture. African Americans, for example, have ~20% European ancestry, so any alleles that are present in Europeans and absent in Sub-Saharan Africans would tend to appear as low-frequency alleles in African Americans.

It is an open question to what degree modern human differences in the presence of low-frequency alleles are due to bottlenecks (such as the Out-of-Africa event) and to what degree they are due to admixture with other non-modern groups. A recent paper discovered a signal of Neandertal admixture when one considered alleles with 10% or less frequency in Europeans.

In the case of African Americans, we can tell that some of their low-frequency alleles were acquired by admixture with Europeans, because we have European samples; and, in the case of Europeans, we can tell that some of their low-frequency alleles were acquired by admixture with Neandertals, because we have a Neandertal genome. But, we don't have many of the genomes of archaic human groups that may have contributed variants to modern humans (and in some cases, like the Denisovans, we did not even know they existed in the first place!), so we must always keep in mind the possibility that such alleles may lurk on the left side of the AFS.

arXiv:1301.1729 [q-bio.PE]

A genome-wide survey of genetic variation in gorillas using reduced representation sequencing

Aylwyn Scally et al.

All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. To date, however, genetic studies within these species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,274,491 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.

Link

Longer time scale for human evolution (Hawks 2012)

Scally and Durbin published a recent review on the implications of a slower human autosomal mutation rate, and now John Hawks has a commentary on the same topic in PNAS (pdf; paywall). He goes through a lot of the evidence of early fossil hominins and ape and mentions several examples that harmonize with the slower mutation rate. As expected, he also finds a better agreement of the slow mutation rate with the evidence for Neandertals where 530,000 year old finds from Atapuerca show signs of belonging to the Neandertal lineage, a date that is inconsistent with a late divergence of modern humans and Neandertals. Finally, he has this to say about modern humans:

Across this same time scale, the archaic ancestors of today’s Africans had already developed an intricate population structure. Genomic investigation of African hunter–gatherers has opened new windows onto this deep genetic history of differentiation and introgression (14, 15), bringing the origin of modern African diversity into the population structure of the early Middle Pleistocene. A simple hypothesis of modern human origins in a bottlenecked population cannot account for this diverse genetic history.    

The mtDNA time scale now poses a hanging question. Mitochondrial mutations occur much more often than nuclear DNA mutations, with greater heterogeneity among sites (16). Still, our estimate of mtDNA substitution rates depends on our estimates of branch lengths of the primate phylogeny. Until now, mitochondrial comparisons have been the strongest evidence in favor of a short time scale for the dispersal and differentiation of non-African peoples, within the past 70,000 y (17). Some recent attempts to examine the relationships of non-African populations using nuclear genome data have led to time scales in excess of 100,000 y (18), and others favor more recent estimates (19). Despite the recency of this work, most authors have continued to use an outdated fast molecular clock and short generation time estimates. As we move forward, such results will need to be corrected or adjusted to enable comparisons with current work. 

There is a very interesting question here, which I've mentioned before, but is worth repeating: admixture between divergent lineages can inflate split times. Acceptance of the slow autosomal mutation rate will result in split times in excess of 100 thousand years for Africans vs. non-Africans, and perhaps 300 thousand years for African hunter-gatherers. On the other hand, the mtDNA clock (haplogroup L3 = 70ky), no matter how it is recalibrated is unlikely to match these old dates, and the Y-chromosome clock (current estimate of its root a little more than 100 ky, and of the dominant African lineage E on the cusp of the LSA) will certainly not match them.

In my opinion, it will slowly become apparent that the way to harmonize our picture of human origins is to accept a substantial degree of archaic admixture in Africa. Such admixture cannot be detected directly, because there are no archaic genomes from Africa, and the hot climate throughout much of the continent may make preservation of DNA more difficult than in northern parts of Eurasia (where Neandertal and Denisovan individuals were from). Nor can it always be detected with LD-based methods, since LD decays exponentially and really old admixture is indistinguishable from an excess of mutation in a large population size. But, its acceptance will simultaneously solve the riddle of excess polymorphism in Africans, remove the need for an Out-of-Africa bottleneck of biblical proportions, and resolve the discrepancy between autosomal and uniparental evidence.