Neandertal Nuclear Genome: Multiregional Evolution is the new Out of Africa

Green and colleagues announced the Neandertal nuclear genome in tomorrow’s issue of the journal Science. Hitherto only complete mitochondrial DNA (mtDNA) genomes had been recovered. These are only inherited maternally, and the genetic differences between the Neandertal mtDNA and that of modern humans seemed to suggest that Neandertals and humans didn’t mix, that is that they were replaced by “anatomically modern humans” (whatever that phrase means). mtDNA is special as far as genetic stuff goes – only inherited maternally, so only tells about one strain out of a slew of ancestors; doesn’t recombine; as a result, selection acting on a part results on selection of the entire mitochondrial genome; oh and it’s certainly not selectively neutral.
So should we have been wary when it was suggested by mtDNA that neandertals and humans were separate species (recall the issue was even crazier with the Denisova mtDNA specimen…)?

This is a big deal, because for the past several decades researchers have debated the nature of modern human origins. On morphological and shaky mtDNA evidence, several researchers have argued that modern humans emerged from a small African population, which then spread throughout the world between 100-200 thousand years ago and replaced all other ‘archaic’ human populations. Intuitively this doesn’t make sense, and today’s neandertal announcement renders the Out of Africa with Replacement model for human origins absolutely untenable.
So, were Neandertals and (even then-modern) humans the same species? Yes! If Neandertals were a different species, we would expect all humans to be equally genetically divergent from neandertals. But this is not what Green and colleagues found. Rather, the genomes of a French person, a Chinese person, and a Papua New Guinean were actually more similar to the Neandertal genomes than the two African human representatives were to the Neandertals. Such disparate divergences mean we’re dealing with genetic variation within a species, rather than between species.
In fact, the authors estimate that about 1-4% of modern, non-African genomes are derived from Neandertals. Plagnol and Wall (2006) estimated around 5% of human genes come from ‘archaic’ humans, so it is good to see corroborating evidence from two sources. It is interesting, however, that earlier candidates for introgression from archaics, such as the microcephalin haplogroup D, do not appear to have come from Neandertals (maybe another archaic population, then?).
The authors were also able to use these neandertal and modern human genomes to estimate regions of the human genome that have been under recent and accelerated evolution, including:
  • SPAG17 is associated with sperm motility – is this evidence for sperm competition and recent sexual selection?
  • Regions in which, among modern humans, mutations are associated with social-cognitive diseases like schizophrenia and autism
  • RUNX2, again where misexpression in humans is associated with dysgenesis of frontal bone (forehead), shoulder and rib-cage shape morphology
I think the only things I would have loved to have seen in this study are simple logistical issues, things that are probably simply not practical at the moment because of technological constraints. First, I’d love to see a much larger set of modern human reference genomes. The study included only 2 human nuclear genomes from sub-Saharan Africa, 1 from Europe, 1 from China and 1 from Papua New Guinea. Yes, this samples variation from all over the world, but it’s 5 out of nearly 7 billion genomes out there today. At the moment, however, it’s just not that easy to acquire and handle genomic data for many individuals.
Second, I’d like to see nuclear genome comparisons using Upper Paleolithic modern humans – ‘modern human’ contemporaries of Neandertals. The Denisova mtDNA was surprising because, at some 40 ka, its genome was about twice as different from modern humans as the neandertal mtDNA sequences were. Just what kind of genetic diversity are we looking at in ancient (anatomically both ‘archaic’ and ‘modern’) humans?
Green and colleagues should be lauded because of how meticulously they went about this project. They took major pains to circumvent issues of contamination, they maximized the DNA they could obtain in spite of preservation issues, they came up with some clever tests. And their results are really interesting.
Green RE et al. 2010. A draft sequence of the Neandertal genome. Science 328: 710 – 722.
Plagnol V and Wall JD. 2006. Possible Ancestral Structure in Human Populations. PLoS Genetics 2(7): e105

A Tale of Two Lineages

[Hey, I’ll bet I’m the first person to make that allusion…]
In a paper published in JHE today, M. Schillaci posits that human facial anatomy suggests the existence of two human lineages in the late Pleistocene. Schillaci’s analysis reveals that faces of early Australasian crania (40-8 ka) are very similar to those of Levantine specimens Skhul 5, Qafzeh 6 and Qafzeh (100-90 ka). The overall results of the study suggest that the Australasian and Levantine populations share an earlier common ancestor than modern humans, including Upper Paleolithic Europeans. Schillaci interprets this to mean that modern humans first dispersed from Africa around 100 ka, long before the supposed “revolution” of Paleolithic Europe, and made it as far as Australia; second dispersal then occurred some 50 ka later.

The article brings up the issue of Out-of-Africa (Replacement) vs. Multiregional models, but does not clearly come out directly in favor of either one. But by setting up a scenario in which two human lineages are present throughout the Old World in the last 100 ka, the possibility is opened up for these lineages to accrue genetic differences simply by drift or even by selection, then to come into contact again and admix, and for the “archaic” genes to be incorporated into the newer (and modern) genome (introgressive hybridization; cf Evans et al. 2006, Garrigan and Kingan 2007, Hawks and Cochran 2006).

Schillaci does note that the Levantine sample

exhibits a slightly closer genetic relationship to Neandertals (d=0.7318) than to Upper Paleolithic Europeans (d=0.7483). . . . This observed relationship is probably not the result of phenotypic convergence, and likely reflects a slightly more recent common ancestry and/or perhaps hybridization between early modern humans and Neandertals (Trinkaus, 2007). (p. 6)

However, he later notes,

In the present study, the relationship between early modern humans from the Levant and early Australasians (d=0.348) is more than 2.1 times closer than between early modern humans and Neandertals (d=0.7318), and Neandertals do not show a close relationship with early Australasians (d=1.2615). If the observed relationship between Neandertals and early modern humans is the product of hybridization, there is no craniometric evidence indicating that there was substantial introgression of Neandertal alleles into the dispersing modern human population… (p. 7)

Can Schillaci make these claims about “genetic relationship[s]” based on his data? Let’s look at the opening line of the abstract: “This study examines the genetic affinities of various modern human groupings using a multivariate analysis of morphometric data.” A rewording might be: This study examines the craniofacial affinities of various modern human groupings, and to thereby infer genetic relationships. Basically, Schillaci assumes that genetic relationships between populations are accurately reflected in facial anatomy, a bold statement to make. Indeed, he acknowledges the problems with this assumption, but also cites studies (which I haven’t yet read) suggest that craniometric variation in humans throughout the world fits a neutral model of genetic variation. So, Schillaci talks about genetic relationships throughout the paper, but these aren’t based on actual genetic data, but rather inferences from craniometric data–quite confusing. His aforementioned lack of evidence for introgression between neandertals and early modern humans does not preclude real genetic evidence for introgression (cf. what I cf-ed above.)

What I care about: the study allows for, and possibly corroborates, a Multiregional model of human evolution (of course, what I really care about is the possibility of such a model prior to, and in the early stages of, the genus Homo). Hey, I guess old-school craniometrics hasn’t outlived its usefulness in physical anthropology.

Evans PD et al. 2006. Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage. Proc Nat Acad Sci 103(48): 18178-18183.

Garrigan D and SB Kingan. 2007. Archaic Human Admixture. Curr Anthropol 48(6): 895-902.

Hawks J and GM Cochran. 2006. Dynamics of adaptive introgression from archaic to modern humans. Paleoanthropol 4: 101-115.

Schillaci M, in press. Human cranial diversity and evidence for an ancient lineage of modern humans. J Hum Evol xx: 1-13.