Murderous chimps

Nature 513, 414–417 (18 September 2014) doi:10.1038/nature13727

Lethal aggression in Pan is better explained by adaptive strategies than human impacts

Michael L. Wilson et al.

Observations of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) provide valuable comparative data for understanding the significance of conspecific killing. Two kinds of hypothesis have been proposed. Lethal violence is sometimes concluded to be the result of adaptive strategies, such that killers ultimately gain fitness benefits by increasing their access to resources such as food or mates1, 2, 3, 4, 5. Alternatively, it could be a non-adaptive result of human impacts, such as habitat change or food provisioning6, 7, 8, 9. To discriminate between these hypotheses we compiled information from 18 chimpanzee communities and 4 bonobo communities studied over five decades. Our data include 152 killings (n = 58 observed, 41 inferred, and 53 suspected killings) by chimpanzees in 15 communities and one suspected killing by bonobos. We found that males were the most frequent attackers (92% of participants) and victims (73%); most killings (66%) involved intercommunity attacks; and attackers greatly outnumbered their victims (median 8:1 ratio). Variation in killing rates was unrelated to measures of human impacts. Our results are compatible with previously proposed adaptive explanations for killing by chimpanzees, whereas the human impact hypothesis is not supported.

Link

Chimp mutation rate is equal to human mutation rate but driven more by males

This is important because (a) it shows evidence for the "slow" mutation rate in a species related to humans, (b) it shows that chimp and human mutation rates are equal and so using the human mutation rate in studies of divergence with chimps is justified, and (c) it is driven differently by males/females than in humans.

Science 13 June 2014: Vol. 344 no. 6189 pp. 1272-1275
DOI: 10.1126/science.344.6189.1272

Strong male bias drives germline mutation in chimpanzees

Oliver Venn

ABSTRACT

Germline mutation determines rates of molecular evolution, genetic diversity, and fitness load. In humans, the average point mutation rate is 1.2 × 10−8 per base pair per generation, with every additional year of father’s age contributing two mutations across the genome and males contributing three to four times as many mutations as females. To assess whether such patterns are shared with our closest living relatives, we sequenced the genomes of a nine-member pedigree of Western chimpanzees, Pan troglodytes verus. Our results indicate a mutation rate of 1.2 × 10−8 per base pair per generation, but a male contribution seven to eight times that of females and a paternal age effect of three mutations per year of father’s age. Thus, mutation rates and patterns differ between closely related species.

Link

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

AAPA 2013 abstracts

The program of the 2013 meeting of the American Association of Physical Anthropologists is now online (pdf). As always, there is plenty of interest here, so I'll just highlight a few titles that caught my eye; feel free to add more in the comments.


Neolithic human mitochondrial haplogroup H genomes and the genetic origins of Europeans.

Haplogroup (hg) H dominates present-day Western European mitochondrial (mt) DNA variability (>40%), yet was less prevalent amongst early Neolithic farmers (~19%) and virtually absent in Mesolithic hunter-gatherers. To investigate this haplogroup’s significance in the maternal population history of Europeans we employed novel techniques such as DNA immortalization and hybridization-enrichment to sequence 39 hg H mt genomes from ancient human remains across a transect through time in Neolithic Central Europe. The results of our population genetic analyses reveal that the current patterns of diversity and distribution of hg H were largely established during the Mid-Neolithic, but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers, which expanded out of Iberia in the Late Neolithic (~2800 BC). Using a strict diachronic approach allowed us to reconcile ‘real-time’ genetic data from the most common European mtDNA hg with cultural changes that took place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. This revealed the Late Neolithic (2800-2200 BC) as a dynamic period that profoundly shaped the genetic landscape of modern-day Europeans. Furthermore, linking ancient hg H genome sequences to specific points in time by using radiocarbon dates as tip calibrations allowed us to reconstruct a precise lineage history of hg H and to calculate a mutation rate 45% higher than traditional estimates based on the human/chimp split.

Preliminary research on hereditary features of Yinxu Population.

... The 37 individuals sampled in this study have been discovered in middle to small size burials, and therefore constitute a representative sample to study Yinxu commoners’ society. Mitochondrial DNA analysis showed that the Yinxu population included the haplogroups D, G, A, C, Z, M10, M*, B, F and N9a. According to the analysis of molecular variance, the distribution frequency and the rare published data, the Yinxu population shows a closest genetic affinity with the populations of Dadianzi and Zhukaigou early Bronze Age sites (Inner Mongolia), but a more distant relation to the historical period populations. The Yinxu population is also very similar to the modern northern Han Chinese. ... 

Investigating lactase persistence in a Medieval German cemetery: A step towards understanding the rise of the European lactase persistence polymorphism (-3910C/T).

Previous ancient DNA-based studies on the Neolithic found that the incidence of LP falls below detection levels in most regions. Our research shows that between the Neolithic and Medieval periods, the frequency of LP rose from near 0% to over 50%. Also, given that the frequency of LP genotypes in modern-day Germany is estimated at 78.5%, our results indicate that rather than being stable by the Medieval period, the lactase persistent genotype has continued to increase in frequency over the last 1000 years. This new evidence sheds light on the dynamic evolutionary history of the European lactase persistent trait and its global cultural implications.

 New Neanderthal remains from Kalamakia cave, Mani peninsula, Southern Greece.

Peeling back the layers: additional evidence for the date of the Petralona skull (Homo heidelbergensis), Greece.

,.. We conclude that there is no white sinter deposited directly on the skull and therefore the initial date of the skull given by Henning et al. and Grun’s revised date of ca. 200 ka are correct.

Analysis of archaic introgression in Ötzi the Tyrolean Iceman, a 5300 year-old prehistoric modern human.

... We carried out a series of comparisons to address these questions. By examining the Neandertal similarity of individuals from the 1000 Genomes Project, we have substantially expanded the sample of Neandertal-human comparisons. We also examined the genome of the Tyrolean Iceman, a European from approximately 5300 years ago. This is the first comparison of Neandertal genomes to the genome of a prehistoric modern human individual.

A quantitative approach for late Pleistocene hominin brain size.

... The results of our study show that Neanderthals have smaller brains than the Pleistocene AMH despite the fact that the latter are smaller in body mass. However, the Holocene AMH (7 populations) have smaller brain sizes than those of Neanderthals. ...

Re-evaluating the functional and adaptive significance of Neandertal nasofacial anatomy.

... Among Middle and Late Pleistocene Homo, there is evidence that nasal morphology varies with climate, albeit within an archaic architectural nasofacial framework. Neandertal internal nasal dimensions are greater in both height and length than archaic humans from sub-Saharan Africa. Furthermore, while other aspects of the nose are relatively broad, superior internal breadth dimensions in Neandertals are narrowed relative to sub-Saharan archaics. These differences parallel those seen in modern humans, indicating that Neandertals had an increased capacity for nasal heat and moisture exchange over their African counterparts and thus exhibit clear evidence for cold-climate adaptation. 

Chromosomal rearrangements and human-chimp speciation

Mol Biol Evol (2012) doi: 10.1093/molbev/mss272

Recombination Rates and Genomic Shuffling in Human and Chimpanzee—A New Twist in the Chromosomal Speciation Theory

Marta Farré et al.

A long-standing question in evolutionary biology concerns the effect of recombination in shaping the genomic architecture of organisms and, in particular, how this impacts the speciation process. Despite efforts employed in the last decade, the role of chromosomal reorganizations in the human–chimpanzee speciation process remains unresolved. Through whole-genome comparisons, we have analyzed the genome-wide impact of genomic shuffling in the distribution of human recombination rates during the human–chimpanzee speciation process. We have constructed a highly refined map of the reorganizations and evolutionary breakpoint regions in the human and chimpanzee genomes based on orthologous genes and genome sequence alignments. The analysis of the most recent human and chimpanzee recombination maps inferred from genome-wide single-nucleotide polymorphism data revealed that the standardized recombination rate was significantly lower in rearranged than in collinear chromosomes. In fact, rearranged chromosomes presented significantly lower recombination rates than chromosomes that have been maintained since the ancestor of great apes, and this was related with the lineage in which they become fixed. Importantly, inverted regions had lower recombination rates than collinear and noninverted regions, independently of the effect of centromeres. Our observations have implications for the chromosomal speciation theory, providing new evidences for the contribution of inversions in suppressing recombination in mammals.

Link

Ann Gibbons on slower mutation rate

I have covered several studies on the slower mutation rate and its implications, including a couple of recent overviews by Hawks and Scally and Durbin. Ann Gibbons has come up with yet another take on the matter in Science. There is also a freely available podcast on the topic; you can read the transcript. A couple of quotes from this interview:

Eight new studies in the past three years, and an older study, have all calculated the  mutation rate directly.  This is sort of the result of new high-throughput genome  sequencing methods that give you high-quality coverage of the entire genome.  So we’re  able to get the more precise rate, which we sort of said is about an average of 36  mutations in each newborn.  That’s something like a chance of getting 1.2 mutations per  nucleotide site per 100 million years, okay?  So when you think about spreading 36  mutations over three billion nucleic acids or bases in your genome, it comes out to not  very many mutations per generation.  This is the average rate in modern humans per  generation, and it can be converted into a rate per year.  Now there’s a little debate about  how you do that because you have to know exactly how long each generation is.  But new  studies done by Linda Vigilant and her team – a number of primatologists in Germany – have studied the actual generation times using DNA and observations in the field of  chimpanzees and gorillas, and we know them in modern humans.  What this comes out to  is about half the rate that researchers have been using for the past 15 years.  One study by  David Reich at Harvard and his colleagues comes up with a slower rate, but it isn’t half  the rate.  And that raises some questions about whether the new genome methods are  actually catching all the mutations.  We’re sort of at the limits of their resolution.  I think  most geneticists think that the rate is definitely slower.  There is still some debate about  precisely how much slower.  Is it half or a little bit less?   

...   

Yes.  So if you apply the new mutation rate, you get a human-chimpanzee split of about  8.3 million to about 10.1 million years ago, instead of 4-7 million years ago.  So that’s  quite a bit older.  And the earliest fossils of the human family only are about 6-7 million  years, so there’s a problem there.  The human-Neandertal split used to be 250,000 to  350,000 years ago.  Now it’s about 400-600 thousand years ago.  That fits with fossils  that look like they’re ancestral to Neandertals that show up around 500,000 years ago in  Europe.  So that’s a little better fit.  And finally, we date the out-of-Africa migration to  earlier, that we have our modern human ancestors coming out of Africa 90,000-130,000  years ago instead of less than 60,000 years ago.  That would mean some of the fossils that  have been discounted as modern human ancestors – especially in North Africa and  Arabia – might actually be ancestral to modern humans if that’s accurate.  There will be  some debate.  I would say at this point anthropologists and paleogeneticists who use these  dates are quite confused, and they’re taking a wait-and-see attitude to see what geneticists  end up deciding about applying these dates back in time.  

One good thing to come out of the coming upheaval, as anthropologists scramble to update their models, is that the appearance of modern symbolic behavior and art. during the Upper Paleolithic will finally be decoupled from the Out-of-Africa event.

This will help us understand both: the ancestors of non-Africans did not come forth fully formed, like Athena from Zeus's head, having spent millennia of perfecting their craft and honing their minds by perforating shells and scratching lines in some South African cave. Instead, they may been plain old-style hunter-gatherers who stumbled into Asia by doing what they always did: following the food. At the same time, the UP/LSA revolution may not have been effected by a new and improved type of human bursting into the scene and replacing Neandertals and assorted dummies, but rather as a cultural revolution that spread across a species that already had the genetic potential for it, and was already firmly established in both Africa and Asia.

Science 12 October 2012:
Vol. 338 no. 6104 pp. 189-191
DOI: 10.1126/science.338.6104.189

Turning Back the Clock: Slowing the Pace of Prehistory

Ann Gibbons

Researchers have used the number of mutations in DNA like a molecular clock to date key events in human evolution. Now it seems that the molecular clock ticks more slowly than anyone had thought, and many dates may need to be adjusted. Over the past 3 years, researchers have used new methods to sequence whole human genomes, allowing them to measure directly, for the first time, the average rate at which new mutations arise in a newborn baby. Most of these studies conclude that the mutation rate in humans today is roughly half the rate that has been used in many evolutionary studies since 2000, which would make genetic estimates of dates older than previously believed. The question now is how much older?

Link

A surprising link between Africans and Denisovans

I took the following populations from the version of the HGDP released by Patterson et al. (2012). I use the _AHOA suffix (Affymetrix Human Origins Array) to distinguish them from other versions of the same populations:

• MbutiPygmy_AHOA 11
• Italian_AHOA    11
• Miao_AHOA       10
• Papuan_AHOA     12
• Karitiana_AHOA  8

I identified the following SNP subsets:

• AFRICA: 67022 SNPs that were polymorphic in MbutiPygmy and monomorphic in the other populations
• EURASIA: 94858 SNPs that were polymorphic in at least one non-African population and monomorphic in MbutiPygmy
• AFRICA_EURASIA: 367051 SNPs that were polymorphic in both MbutiPygmy and at least one non-African population
• ALL: 528931 SNPs that were polymorphic in at least one population
• GLOBAL: 168640 SNPs that were polymorphic in all 5 populations

Note that the union of AFRICA, EURASIA, and AFRICA_EURASIA is the ALL set.

Here is a Venn diagram of SNP sharing:

I then calculated all D-statistics of the following form:

D(Pop1, Pop2; Archaic, Chimp)

where Archaic is either Neandertal or Denisova, and Pop1, Pop2 is any possible pair of the modern populations. These D-statistics were calculated for all 5 SNP subsets.

Below, you can find all D-statistics, followed by their Z-scores

Pop1 Pop2 Archaic Chimp D-AFRICA D-EURASIA D-AFRICA_EURASIA D-ALL D-GLOBAL Z-AFRICA Z-EURASIA Z-AFRICA_EURASIA Z-ALL Z-GLOBAL
Italian_AHOA MbutiPygmy_AHOA Neander_AHOA Chimp_AHOA 0.3357 0.1231 0.0038 0.0297 -0.0041 19.575 6.041 1.099 8.052 -0.882
Italian_AHOA Miao_AHOA Neander_AHOA Chimp_AHOA 0 -0.0393 -9e-04 -0.0044 8e-04 0 -3.271 -0.251 -1.161 0.184
Italian_AHOA Karitiana_AHOA Neander_AHOA Chimp_AHOA 0 -0.0243 3e-04 -0.0019 0.0067 0 -1.765 0.063 -0.43 1.406
Italian_AHOA Papuan_AHOA Neander_AHOA Chimp_AHOA 0 -0.0348 -0.0088 -0.0113 -0.0017 0 -2.212 -2.027 -2.335 -0.341
MbutiPygmy_AHOA Miao_AHOA Neander_AHOA Chimp_AHOA -0.3357 -0.1646 -0.0046 -0.0331 0.0048 -19.575 -7.399 -1.208 -7.949 0.998
MbutiPygmy_AHOA Karitiana_AHOA Neander_AHOA Chimp_AHOA -0.3357 -0.147 -0.0036 -0.0311 0.0104 -19.575 -6.089 -0.821 -6.852 2.013
MbutiPygmy_AHOA Papuan_AHOA Neander_AHOA Chimp_AHOA -0.3357 -0.1467 -0.0114 -0.0387 0.0024 -19.575 -6.381 -2.661 -7.947 0.45
Miao_AHOA Karitiana_AHOA Neander_AHOA Chimp_AHOA 0 0.0165 0.0013 0.0027 0.0061 0 1.263 0.296 0.63 1.291
Miao_AHOA Papuan_AHOA Neander_AHOA Chimp_AHOA 0 8e-04 -0.0083 -0.0074 -0.0025 0 0.05 -1.987 -1.631 -0.532
Karitiana_AHOA Papuan_AHOA Neander_AHOA Chimp_AHOA 0 -0.0136 -0.0094 -0.0099 -0.0083 0 -0.804 -1.861 -1.853 -1.568
Italian_AHOA MbutiPygmy_AHOA Denisova_AHOA Chimp_AHOA 0.2354 -0.1057 -0.0102 -0.0014 -0.0147 13.01 -5.396 -2.806 -0.378 -3.156
Italian_AHOA Miao_AHOA Denisova_AHOA Chimp_AHOA 0 -0.0131 0.0023 0.0012 0.0058 0 -1.193 0.713 0.369 1.452
Italian_AHOA Karitiana_AHOA Denisova_AHOA Chimp_AHOA 0 -0.0046 -0.0024 -0.0025 -0.0012 0 -0.364 -0.563 -0.623 -0.255
Italian_AHOA Papuan_AHOA Denisova_AHOA Chimp_AHOA 0 -0.1248 -0.0349 -0.0421 -0.0193 0 -8.966 -7.553 -9.218 -3.71
MbutiPygmy_AHOA Miao_AHOA Denisova_AHOA Chimp_AHOA -0.2354 0.0808 0.0121 0.0023 0.0199 -13.01 3.832 3.24 0.617 4.251
MbutiPygmy_AHOA Karitiana_AHOA Denisova_AHOA Chimp_AHOA -0.2354 0.0939 0.0082 -7e-04 0.013 -13.01 4.085 1.853 -0.16 2.596
MbutiPygmy_AHOA Papuan_AHOA Denisova_AHOA Chimp_AHOA -0.2354 -0.0781 -0.0201 -0.0343 -0.0042 -13.01 -3.458 -4.554 -7.527 -0.795
Miao_AHOA Karitiana_AHOA Denisova_AHOA Chimp_AHOA 0 0.0092 -0.0051 -0.004 -0.0069 0 0.718 -1.221 -0.996 -1.503
Miao_AHOA Papuan_AHOA Denisova_AHOA Chimp_AHOA 0 -0.1158 -0.0391 -0.0455 -0.0253 0 -8.253 -8.608 -10.045 -5.24
Karitiana_AHOA Papuan_AHOA Denisova_AHOA Chimp_AHOA 0 -0.1242 -0.034 -0.0414 -0.0176 0 -7.973 -6.447 -7.892 -3.195

Some brief observations, before we get to the "main course" of this post:

• Eurasians appear substantially Neandertal/Denisovan-admixed when SNPs polymorphic in Africans and monomorphic in Eurasians are used. I can think of no other explanation than archaic African admixture for this finding.
• Papuans appear Denisovan-admixed across the board. 
• For the GLOBAL set, population differences in Neandertal admixture are all non-signficant. Given that the GLOBAL set includes SNPs likely to have existed in the ancestral modern humans, this indicates a fairly symmetrical relationship of to Neandertals.

The most unexpected and surprising finding, is doubtlessly, the evidence that Africans have more Denisovan ancestry than all Eurasians (except Papuans) when SNPs polymorphic in non-Africans and monomorphic in Africans are used (EURASIA panel). I highlight some comparisons:

First of all, clearly Papuans have a special relationship with Denisovans compared to all the remaining 4 populations:

Italian_AHOA Papuan_AHOA ; Denisova_AHOA Chimp_AHOA -0.1248 -8.966

MbutiPygmy_AHOA Papuan_AHOA ; Denisova_AHOA Chimp_AHOA -0.0781 -3.458

Miao_AHOA Papuan_AHOA ; Denisova_AHOA Chimp_AHOA -0.1158 -8.253

Karitiana_AHOA Papuan_AHOA ; Denisova_AHOA Chimp_AHOA -0.1242 -7.973

But, look at this:

Italian_AHOA MbutiPygmy_AHOA ; Denisova_AHOA Chimp_AHOA -0.1057 -5.396

MbutiPygmy_AHOA Miao_AHOA ; Denisova_AHOA Chimp_AHOA 0.0808 3.832

MbutiPygmy_AHOA Karitiana_AHOA ; Denisova_AHOA Chimp_AHOA 0.0939 4.085

That's right: Mbuti Pygmies are actually closer to Denisovans than Eurasians over the subset of SNPs that are polymorphic in Eurasians and monomorphic in the Mbuti.

I do not quite know what to make of this surprising signal. I can think of two explanations:

1. An early Out-of-Africa movement that affected "Denisovans" and Papuans but not other Eurasians. Living Africans are pulled away from Denisovans because of their archaic African ancestry and towards them because of contributions from their ancestors to the Denisovan population. Hence, they appear less Denisovan-like in African-polymorphic sites (where there is an excess of archaic admixture in Africans) and more Denisovan-like in African-monomorphic sites.
2. An Into-Africa movement of a population related to Denisovans, a kind of "reverse bottleneck" where a subset of Denisova-like variation entered Africa, hence leaving Eurasians polymorphic and Africans monomorphic.

I would like to stress that these results do not really depend on the choice of the MbutiPygmy population. I have also seen them when I carried out similar experiments using Yoruba and Mandenka.

I often get the feeling that the problem of human origins as it stands is one of too little data for too many variables. But, I am more or less convinced that admixture between very divergent populations of Homo heidelbergensis played a major role in shaping modern humans. 

UPDATE (29 Sep): I continue the investigation of this link in a new post.

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.

Or, maybe they speciated 3.7-6.6Ma ago? (Sun et al. 2012)

This has certainly been an eventful August in human origins research; if the Neandertal Wars weren't enough, a different issue that had simmered for a while now, the human autosomal sequence mutation rate, has now come to a full boil.

A couple of weeks ago, Langergraber et al. (2012) came out, and combined direct measurement of generation lengths in humans and other primates with the directly measured human autosomal sequence mutation rate to argue for an old 7-13Ma divergence between Pan and Homo.

Yesterday, Kong et al. (2012) independently derived a low direct mutation rate of 1.2x10^-8, and added the observation that older human fathers pass on more mutations to their offspring than younger ones. As I point out in my post on the topic, this has implications for the Homo-Pan divergence as well: if chimp dads are younger than human dads, they will tend to pass fewer mutations to their offspring. Thus, the chimp mutation rate (/generation) might be lower rather than equal to the human one, and this might push the speciation time even further back in time.

Today, a new paper has appeared in Nature Genetics which argues for an "intermediate" rate between  the direct ~1-1.3x10^-8 rate and the widely used 2.5x10^-8 one: their rate estimate is: 1.4–2.3x10^-8 and the corresponding Human-Chimp speciation time is 3.7-6.6 million years ago. Kari Stefansson is a co-author of the new paper, as he is of the Kong et al. one, which estimated the mutation rate at 1.2x10^-8.

The new paper builds what appears to be a very exhaustive model of microsatellite mutation:

Microsatellites have been widely used to make inferences about evolutionary history. However, the accuracy of these inferences has been limited by a poor understanding of the mutation process. We developed a new model of microsatellite evolution (Supplementary Note). This model can estimate the time to the most recent common ancestor (TMRCA) of two samples at a microsatellite by taking into account (i) the dependence of the mutation rate on allele length and parental age (Fig. 2a,c); (ii) the step size of mutations (Fig. 2b); (iii) the size constraints on allele length (Fig. 2d and Supplementary Figs. 8 and 9); and (iv) the variation in generation interval over history. In contrast to the generalized stepwise mutation model (GSMM), which predicts a linear increase of average squared distance (ASD) between microsatellite alleles over time, the new model predicts a sublinear increase (Fig. 3) and saturation of the molecular clock, due to the constraints on allele length. We also extended the model to estimate the sequence mutation rate, using the per-nucleotide diversity flanking each microsatellite as an additional datum. To implement the model, we used a Bayesian hierarchical approach, first generating global parameters common to all loci, followed by locus-specific parameters and finally the microsatellite alleles at each locus (Online Methods). We used Markov chain Monte Carlo to infer TMRCA and sequence mutation rate. 

I haven't delved deeply into the details of how the sequence mutation rate (per nucleotide/per generation) can be derived by exploiting the microsatellite rate. But, why would the rate estimated with the new method be different than the directly measured one? The authors propose some ideas:

We hypothesize that the lower mutation rate estimates from the whole-genome sequencing studies might be due to (i) the limited number of mutations detected in these studies, which explains why their confidence intervals overlap ours, (ii) possible underestimation of the false negative rate in the whole-genome sequencing studies or (iii) variability in the mutation rate across individuals, such that a few families cannot provide a reliable estimate of the population-wide rate.  

 Apparently, the team behind Sun et al. became aware of the new Kong et al. after the paper was accepted, so they attached the following note at the end of it, as well as a discussion in the supplement:

Note added in proof: After this paper was accepted, another study35 was published that independently estimates the human sequence mutation rate, using a direct measurement in contrast to the indirect measurement we report here. In spite of some key similarities between our results and those of Kong et al.35 (the male-to-female mutation rate ratio and the absence of an effect of mother's age), they estimate a considerably stronger effect of father's age and an overall sequence mutation rate below the range we infer. The discrepancies in the sequence mutation rate may be in part due to the fact that Kong et al. focus on a more intensively filtered subset of the human genome than we analyze here, but other factors are also likely to be at work (Supplementary Note). As an initial attempt to compare the two studies in terms of their implications for evolutionary history, we ran the same Bayesian inference procedure we developed in this paper (integrating over uncertainty in unknown parameters), now using the sequence-based estimates rather than the microsatellite-based estimates as input (Supplementary Note). Notably, the inferred dates based on the measurement of the sequence mutation rate are older and no longer in direct conflict with the inference that S. tchadensis is on the human lineage since the split from chimpanzees. The sequence- and microsatellite-based data sets are very different, and an important direction for future research will be to understand why the direct sequence–based mutation rate estimate is lower than the one inferred on the basis of microsatellites. 

All this leaves me rather perplexed. I guess one take-home lesson from the debate would be to avoid making strong statements about the past that are dependent on a particular mutation rate. The following table from the supplementary material pretty much says it all:

Notice that the two estimates are approximately double one of the other. Personally, I tend to favor the older dates, since they might "match" better with key developments: Out-of-Africa will become pre-100ka and consistent with the appearance of the Nubian technocomplex in Arabia, which seems to be the only real solid evidence of Out-of-Africa in the archaeological record. It would also be consistent with the appearance of modern humans in the Levant c. 100ca at Mt. Carmel, the first clear evidence of Homo sapiens in Eurasia. Moreover, it would explain the early appearance of Neandertaloid features in the Atapuerca hominins at c. 600ka, long before the inferred split of modern humans from Neandertals when the slowest rate is used.

But, my confidence in these correspondences is low until the controversy is resolved one way or another. If the 1.8x10^-8 rate of this paper is closer to the truth, then my money would be on the false negative rate, i.e., full genome sequencing is systematically overlooking SNPs that exist in the genomes.

Apparently, now, we have three rates to contend with: (i) the Icelandic 1.2x10^-8 rate (and other similar rates, such as the 1.36x10^-8 one); the 2.5x10^-8 one that has been very widely used in the literature, and (iii) the "1.82x10^-8 mutations per base pair per generation (90% CI 1.40–2.28 × 10-8; Table 2)" from this paper. This may be disheartening, but all setbacks represent opportunities to learn something new, and now that the issue is out in the open, I'm sure that many "top dogs" will try to figure out what is going on.

Nature Genetics doi:10.1038/ng.2398

A direct characterization of human mutation based on microsatellites

James X Sun et al.

Mutations are the raw material of evolution but have been difficult to study directly. We report the largest study of new mutations to date, comprising 2,058 germline changes discovered by analyzing 85,289 Icelanders at 2,477 microsatellites. The paternal-to-maternal mutation rate ratio is 3.3, and the rate in fathers doubles from age 20 to 58, whereas there is no association with age in mothers. Longer microsatellite alleles are more mutagenic and tend to decrease in length, whereas the opposite is seen for shorter alleles. We use these empirical observations to build a model that we apply to individuals for whom we have both genome sequence and microsatellite data, allowing us to estimate key parameters of evolution without calibration to the fossil record. We infer that the sequence mutation rate is 1.4–2.3-10^-8 mutations per base pair per generation (90% credible interval) and that humanchimpanzee speciation occurred 3.7–6.6 million years ago.

Link

More mutations in children of older fathers, and how it relates to human origins

Most of the coverage of the new Kong et al. paper has focused on the rising risk for inheritable diseases such as autism and schizophrenia in the children of older fathers. And, indeed, that is is the larger story, and, perhaps, the more useful one for society.

But, for those of us interested in the origins of our species, there is another story:

We show that in our samples, with an average father’s age of 29.7, the average de novo mutation rate is 1.20 × 10−8 per nucleotide per generation.

This mutation rate is in line with other direct measured rates, and is about twice smaller than the widely used 2.5x10^-8 rate used in evolutionary studies. Application of the low rate has led to a much older Human-Chimp divergence than was previously thought. That, in turn, will make mitochondrial Eve much older, because the mtDNA clock is calibrated on the Human-Chimp divergence. Practically every study of the last 10 years that looked at human origins and used the 2.5x10^-8 rate needs to be dusted off and made up to date.

But there is yet another story. The beauty of the Langergraber et al. paper is that it inferred the Human-Chimp divergence on the basis of directly observed quantities: mutation rates and generation times. But, there was one quantity which they could not measure directly: the mutation rate in the apes. Thus, they used the mutation rate of humans for the apes as well; that is very reasonable, because presumably the same underlying chemical machinery affects the rate in humans and their simian friends. But, here's where things get complicated:

Mean human paternal ages are about ~7 years older than chimp ones, and ~10 years older than gorilla ones. What this means, is that on average, younger chimp dads and younger gorilla dads have babies. But, the new Kong et al. paper:

Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years.

A back-of-the envelope calculation suggests that the higher age of human fathers may contribute ~30-50% more mutation in humans than in chimps/gorillas. Conversely, the mutation rate used for chimps should not be the human one: it should be even lower.

What are the implications of this?

The divergence of Humans from Chimps has been estimated by summing up mutations on two branches to their most recent common ancestor (MRCA). Younger chimp fathers = lower mutation rate / generation = Chimp-to-MRCA branch just got older.

In other words, just as we learned than humans diverged from chimps ~7-13 million years ago, it may be that they did so even earlier.

Nature 488, 471–475 (23 August 2012) doi:10.1038/nature11396

Rate of de novo mutations and the importance of father’s age to disease risk

Augustine Kong et al.

Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent–offspring trios at high coverage. We show that in our samples, with an average father’s age of 29.7, the average de novo mutation rate is 1.20???10?8 per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5?years. After accounting for random Poisson variation, father’s age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father’s age on the risk of diseases such as schizophrenia and autism.

Link

Human-chimp divergence date pushed back in time

I recently wrote:

Actually, we are beginning to get a hold of the mutation rate -thanks to the ability to sequence full genomes- but we have absolutely no clue when human-chimp divergence actually happened, at least not within a few million years.)

The context of that post was to highlight the fact that many aspects of recent human origins research, such as estimates of effective population sizes or mutation rates were inextricably linked to calibration with the date of divergence between humans and chimps. But, that date was obscure: paleontologists didn't always seem to agree on what represented a member of the lineage leading to us or a common human-chimp ancestor; and there were circular arguments a-plenty, where genetic mutation rates calibrated on a particular human-chimp divergence were then used again to "prove" that divergence rate.

Well, at least now, thanks to a new paper by Langergraber et al., we have a better idea. It's clear now that humans and chimps diverged from each other a few million years earlier than previously thought.

And, of course there are implications on every event where calibration based on human-chimp divergence was at play. That has major implications for Neandertal-human divergence, as well as for human-human divergence estimates.

Together with the publication of the two conflicting papers on Neandertal admixture (or not), it appears that August 2012 has proven to be anything but a time for a little quiet vacation.

From Science's coverage of the new work:

Now, after a decade of analyzing the patterns of reproduction in chimpanzees and gorillas in Africa, Vigilant and former postdoc Kevin Langergraber—now a primatologist at Boston University—say they have the data they need. Working with almost 20 collaborators, the duo gathered data recording the age of mothers and fathers at the birth of 226 offspring in eight different chimpanzee communities in the wild, and 105 offspring of mountain gorillas from two different research sites in Africa—and they verified those relationships with DNA paternity tests on coprolites gathered in the field. As they report today in the Proceedings of the National Academy of Sciences, chimpanzee mothers ranged in age from 11.7 to 45.4 years at the birth of their offspring. The average age of reproduction was 25 years for females and 24 years for males, giving them an average generation time of about 25 years. Gorilla females ranged in age from 7.3 to 38 years when they gave birth, and the average generation time for both sexes was about 19.3 years. 

... 

To get the mutation rates, the team divided the number of mutations between parents and their offspring (collected by analyzing DNA from coprolites sent to the lab in Leipzig) by the newly calculated generation times. The researchers got a high and low mutation rate for each species per year—rates that were slower than previously estimated using fossils to calibrate the molecular clock. When they applied the new rates to the history of all three species, they calculated that humans and chimps split earlier than expected—at least 7 million to 8 million years ago and possibly as early as 13 million years ago. They estimate the split between gorillas and the lineage leading to humans and chimpanzees to 8 million to 19 million years ago. Those dates have such wide ranges, Vigilant explains, because they assume the mutation rates seen today have been constant over time in all three lineages. So a key remaining question is whether mutation rates were faster in the past.

Incidentally, this might solve Chris Stringer's doubts about the antiquity of the Atapuerca hominins, because it is now possible to reconcile their 600,000-year old age with a genetic date of modern human-Neandertal divergence of 400-800 thousand years.

Any further comments on the paper will be posted in this space after I read it.

UPDATE (Aug 15):

This is a very exciting paper that finally addresses the autosomal mutation rate controversy.

Previously, this rate was assessed by picking a split time for the chimp-human pair, and counting sequence divergence, dividing it by this time. But, this method led to circular reasoning: paleontologists looked at the (very fragmentary and controversial) early fossil record and assigned some arbitrary date to the split.

Then, when new fossils turned up that looked like they belonged to the human lineage but preceded the supposed split, their inclusion in the lineage leading to humans was rejected, on account of them being too old, pre-dating the supposed split!

A different approach is to use the directly observed mutation rate in families. This has been made possible due to the fall in the cost of sequencing. Subsequently, one divides sequence divergence with the mutation rate to obtain generations. But, how does one obtain years, instead of generations? A measure of generation length is needed.

And, this is the exciting and remarkable part: members of the team behind this paper didn't just "guess" the generation length in primates but actually observed primates in the wild, assigning hard parental ages where they could, or intervals where they could not. This was a decades-long process that gave us the best estimates of generation lengths to date.

Armed with this knowledge (directly observed generation lengths + directly observed mutation rates), they were able to go back in time and estimate the human-chimp divergence. Their answer?

As I have said before: this has implications. The authors do not touch on recent human history, except to point out that the Neandertal-human split harmonizes better with paleoanthropology:

analyses of the Neanderthal genome indicated a population split between present-day humans and Neanderthals at 270–440 ka (40). This date appears to conflict with fossil evidence tracing the emergence of Neanderthal morphological characters over the course of the Middle Pleistocene in Europe (41). The earliest evidence for Neanderthal traits was proposed to date to 600 +/- 66 ka at the Sima de Los Huesos (Atapuerca, Spain) (42), thus predating the genetically estimated population divergence times, but this date has been disputed on the basis of both the apparent conflict with the genetic data and on stratigraphic grounds (43). However, even if the early dates for Sima are disregarded, it is clear that fossils from oxygen isotope stage 11 (around 400 ka), such as the Swanscombe cranium, already show clear Neanderthal traits (44). Using the new human– chimpanzee split estimate and assuming generation times between 25 and 29 y would push back the human/Neanderthal split to 423,000–781,000 y, resolving this apparent conflict. 

The authors also propose that:

Whereas the earliest fossil universally accepted to belong to the lineage leading to present-day humans rather than to chimpanzees, Australopithecus anamensis, is 4.2 Ma (31) and thus reconcilable with a molecularly inferred human–chimpanzee split time as recent as 5 Ma, the attribution of late Miocene (5–7 Ma) fossils to the hominin lineage has posed a problem. Our estimates make it possible to reconcile attribution of fossils such as Ardipithecus kaddaba (5.2–5.8 Ma) (32), Orrorin tugenensis (6 Ma) (9), and Sahelanthropus tchadensis (6–7 Ma) (10) to the hominin lineage with speciation times inferred from genetic evidence (Fig. 1). However, our estimates cannot address the controversy of whether specimens such as these truly belong to the lineage leading to present-day humans or to other, closely related lineages (11). 

And, there are calibration points in more recent times that the authors do not consider, but will also support the new mutation rate/speciation time. For example, Gravel et al. obtained a 51ky Out-of-Africa, and sub-30ky dates for the European-Asian split using a mutation rate of 2.38x10^-8. Using the lower mutation rate will bring the European-Asian split up to the 40 thousands (consistent with the first appearance of AMH in both Europe and East Asia), and the OoA event to 100ky, consistent with the appearance of the Nubian Complex in Arabia and the Skhul/Qafzeh hominins in the Levant.

The new mutation rate will also affect other dates. Li and Durbin estimated a 100-120ky Yoruba-Eurasian divergence, but only by using a 2.5x10^-8 rate and explicitly rejecting the slower direct rate. We know for a fact that the major part of Yoruba ancestry is shared with Eurasians in the post-70ky time frame (Y-haplogroup E is part of clade CT, and most Yoruba mtDNA belongs to haplogroup L3, of which Eurasian N and M are branches). In order for a 100-120ky (or 200ky+ with the direct rate) divergence to be believable, only one possibility exists: that Yoruba trace their ancestry to a combination of post-70ky E/L3-bearing people who were quite close to Eurasians but also of a group of Palaeoafricans that split off from modern humans well before 200ky. And, I won't even go to the implications about African hunter-gatherers that are divergent from Eurasians by an even greater amount.

Enjoy the calm before the storm: if people start using the slow mutation rate (as they now must), a lot of the old certainties about our origins will be toppled.

PNAS doi: 10.1073/pnas.1211740109

Generation times in wild chimpanzees and gorillas suggest earlier divergence times in great ape and human evolution

Kevin E. Langergraber et al.

Fossils and molecular data are two independent sources of information that should in principle provide consistent inferences of when evolutionary lineages diverged. Here we use an alternative approach to genetic inference of species split times in recent human and ape evolution that is independent of the fossil record. We first use genetic parentage information on a large number of wild chimpanzees and mountain gorillas to directly infer their average generation times. We then compare these generation time estimates with those of humans and apply recent estimates of the human mutation rate per generation to derive estimates of split times of great apes and humans that are independent of fossil calibration. We date the human–chimpanzee split to at least 7–8 million years and the population split between Neanderthals and modern humans to 400,000–800,000 y ago. This suggests that molecular divergence dates may not be in conflict with the attribution of 6- to 7-million-y-old fossils to the human lineage and 400,000-y-old fossils to the Neanderthal lineage.

Link

Rise of the Planet of the Apes postponed

In Rise of the Planet of the Apes, a young scientist experiments with genetically modified chimpanzees, inadvertently making one exhibit human-like behavior. I thought of the movie as I was listening to the live webcast of Svante Paabo's talk at the Genomes Environments Trait conference (not sure if/when there will be an archival copy of the talks available).

Paabo was discussing how scientists had identified amino acid substitutions in the FOXP2 gene that were fixed in humans and different from chimpanzees, and, more recently -thanks to the availability of the Denisova genome- of differences that were fixed in modern humans and different in our closest genetic relatives (archaic humans).

The question naturally arises: how can we tell what the (modern) human specific mutations actually do.

Paabo said that we could do this if we created transgenic chimps/humans with the human/chimp version of the gene, but then jokingly crossed out the idea since ethics committees would never approve it.

He went on to say that the human version of FOXP2 was input into transgenic mice instead, with some evidence that these mice had different vocalization than regular mice. Even though we cannot actually breed humans with the chimp version of FOXP2, there may actually be some of the 7 billion humans in existence that may harbor back-mutations giving them this version.

Naturally, the question arises: if nature itself mutates human FOXP2 into its chimp version and vice versa, why is it unethical to do so in the lab?


Of course, there are good ethical reasons why we wouldn't want to give human children a chimp gene: we don't exactly know what it will do, but the risk of causing harm to a human person is sufficient reason to act cautiously.

But, why is it unethical to give chimps the human version of the gene? After all, the fact that the human version is fixed (in humans) may mean that is doing something really important and giving us some ability that we shouldn't toy around with. But, what evidence is there that the reverse is also true, and the chimpanzee harboring a human FOXP2 gene would face any problems at all?

This brings me to the topic of a recently introduced bill which would ban chimpanzee research altogether. This would not only subject the issue of chimp research to ethics committees who would probably not approve it, but ban it altogether.

There are substantial benefits in learning more about FOXP2 and other genes in which humans differ from chimpanzees. There is the intellectual benefit of learning what makes us special within nature, and how we differ from apes. There is the practical benefit of potentially easing the suffering of patients with damaged copies of genes that are fixed in the human lineage. Or, of understanding how language ability and cognition emerge, so that we can one day hope to create machines capable of it, freeing mankind from a great deal of toil.

And, there is the infinitesimal potential that we'll end up with an unhappy chimp ready to organize the simian takeover of our planet. Thankfully, Pinky and the Brain do not give rise to the same levels of dread and insecurity, so, for the time being we still have the option of experimentation with mice.

Personally, I'm all for putting human FOXP2 in chimps and seeing what happens. And, I am rather dismayed that the scientific and political culture has become so risk-averse that an experiment that would bring no harm to any humans, that would benefit humans, and that may not, indeed, affect negatively the chimps involved is, nonetheless, rejected out of hand on the basis of the nebulous probability that it might.

Chimpanzee Y-chromosome gene diversity explained

In short (as I understand it):

• Gorilla females tend to have one man, hence there is no sperm competition between different males' sperm
• Orangutan females tend to choose their man, so, once again, there is no sperm competition between different males' sperm
• Bonobos are matriarchal and have concealed ovulation, hence they can also choose the father of their children
• Male chimpanzees pick their female partners, but female partners are not necessarily faithful, hence a race sometimes takes place within female chimps to determine which sperm will impregnate them.

From the paper:

In conclusion, the major findings of this study are: (i) That the contrasting patterns of DAZ and CDY variability in chimpanzees (P. troglodytes) and bonobos (P. paniscus), initially suggested by comparative FISH [11], are similarly reflected by real-time qPCR data. (ii) Although chimpanzee and bonobo share promiscuous mating behaviors, it is only in chimpanzees that male dominance is sufficiently developed to influence sperm competition [62], [63]. This results in high selective pressure on male fertility genes. Bonobos on the other hand, are characterized by a matriarch-dominated societal structure [63,64, reviewed in 65] which, coupled to concealed ovulation [66], permits female mate choice, thus rendering sperm competition redundant. (iii) That monoandrous mating in gorillas (G. gorilla) [37]–[41] and female mate choice in orangutans (P. pygmaeus and P. abelii) [18], [49], [50] similarly accounts for the dearth of intraspecific Y-chromosomal variation in the ampliconic fertility genes DAZ and CDY among Y-chromosomal lineages in these species.

PLoS ONE 6(12): e29311. doi:10.1371/journal.pone.0029311

Y-Chromosome Variation in Hominids: Intraspecific Variation Is Limited to the Polygamous Chimpanzee

Gabriele Greve et al.

Abstract Background

We have previously demonstrated that the Y-specific ampliconic fertility genes DAZ (deleted in azoospermia) and CDY (chromodomain protein Y) varied with respect to copy number and position among chimpanzees (Pan troglodytes). In comparison, seven Y-chromosomal lineages of the bonobo (Pan paniscus), the chimpanzee's closest living relative, showed no variation. We extend our earlier comparative investigation to include an analysis of the intraspecific variation of these genes in gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus), and examine the resulting patterns in the light of the species' markedly different social and mating behaviors.

Methodology/Principal Findings

Fluorescence in situ hybridization analysis (FISH) of DAZ and CDY in 12 Y-chromosomal lineages of western lowland gorilla (G. gorilla gorilla) and a single lineage of the eastern lowland gorilla (G. beringei graueri) showed no variation among lineages. Similar findings were noted for the 10 Y-chromosomal lineages examined in the Bornean orangutan (Pongo pygmaeus), and 11 Y-chromosomal lineages of the Sumatran orangutan (P. abelii). We validated the contrasting DAZ and CDY patterns using quantitative real-time polymerase chain reaction (qPCR) in chimpanzee and bonobo.

Conclusion/Significance

High intraspecific variation in copy number and position of the DAZ and CDY genes is seen only in the chimpanzee. We hypothesize that this is best explained by sperm competition that results in the variant DAZ and CDY haplotypes detected in this species. In contrast, bonobos, gorillas and orangutans—species that are not subject to sperm competition—showed no intraspecific variation in DAZ and CDY suggesting that monoandry in gorillas, and preferential female mate choice in bonobos and orangutans, probably permitted the fixation of a single Y variant in each taxon. These data support the notion that the evolutionary history of a primate Y chromosome is not simply encrypted in its DNA sequences, but is also shaped by the social and behavioral circumstances under which the specific species has evolved.

Link

Should chimpanzees be used in entertainment?

There is an article in Scientific American covering a paper in PLoS ONE, arguing that chimpanzees should not be used on TV or Movies, and should not be used as pets. I will let readers evaluate the arguments for what they are worth, but I will just make a couple of comments:

• I never quite understood the "endangered species" concept. Species come and go, that's Evolution 101 for you. And, some species go because of a new predator that they can't cope with, e.g., man. I am inherently suspicious of an antiquarian mentality that humans are supposed to preserve species as they are today, or even restore them to some older state: if we interfere with evolution, why should it always be to preserve species, and not to cull some of them?
• There are good reasons why we should not want chimpanzees to go extinct, and they have nothing to do with the preservationist imperative. Chimpanzees are our closest relatives, and hence provide an important comparative baseline in studies of human evolution. The study of man and all its intellectual and practical benefits would suffer if there were no chimps around.
• Who decides whether a species is endangered or not? According to the SciAm article, "the global population of wild chimpanzees is only 172,700 to 299,700 individuals." That corresponds to an effective population size well above estimates for the ancestral effective population size of either humans or the common ancestor of humans and chimpanzees.
• It is true that TV and Movies present a distorted picture of chimpanzees. Most chimp appearances make them appear "cute" and "human-like". But, that could be said for nearly every animal on TV. You never see domestic dogs, for example, portrayed as killers on TV, and yet, there are dozens of fatal and many more non-fatal "dog bites man" incidents every year. According to the authors' logic, TV and Movies distort the behavior of dogs, making them appear like "Lassie" when they are in fact are often dangerous animals.
• Nor is it true that if we did not use chimpanzees in TV and Movies we would have an accurate portrayal of them: if you don't watch chimps on TV ads, you will not automatically sit through scientifically-minded documentaries about them. TV and Movies happily portray all sorts of animals, domestic or otherwise in a stereotypical form. Ask a 5-year old whether they like a whole series of animals, and you will get back a whole series of positive and negative stereotypes, some of which go back to Aesop and beyond.
• Should people's exposure to non-human primates in entertainment be limited to CGI creatures like King Kong, the apes in Planet of the Apes, or CGI chimps that will surely take the place of real ones if the use of the latter is outlawed?
• It could be argued that the unprecedented wide-scale breeding and rearing of chimps is the initial stage of a process of domestication of that animal. Surely, early dogs, cats, horses, etc. were dangerous animals compared to modern breeds, but our ancestors did succeed in making them more amenable to human society. Why should it be illegal for people to keep whatever animal they see fit as pets, provided they are (a) not cruel to it, and (b) take proper precautions not to endanger their neighbors?

PLoS ONE 6(10): e26048. doi:10.1371/journal.pone.0026048

Use of “Entertainment” Chimpanzees in Commercials Distorts Public Perception Regarding Their Conservation Status

Kara K. Schroepfer et al.

Chimpanzees (Pan troglodytes) are often used in movies, commercials and print advertisements with the intention of eliciting a humorous response from audiences. The portrayal of chimpanzees in unnatural, human-like situations may have a negative effect on the public's understanding of their endangered status in the wild while making them appear as suitable pets. Alternatively, media content that elicits a positive emotional response toward chimpanzees may increase the public's commitment to chimpanzee conservation. To test these competing hypotheses, participants (n = 165) watched a series of commercials in an experiment framed as a marketing study. Imbedded within the same series of commercials was one of three chimpanzee videos. Participants either watched 1) a chimpanzee conservation commercial, 2) commercials containing “entertainment” chimpanzees or 3) control footage of the natural behavior of wild chimpanzees. Results from a post-viewing questionnaire reveal that participants who watched the conservation message understood that chimpanzees were endangered and unsuitable as pets at higher levels than those viewing the control footage. Meanwhile participants watching commercials with entertainment chimpanzees showed a decrease in understanding relative to those watching the control footage. In addition, when participants were given the opportunity to donate part of their earnings from the experiment to a conservation charity, donations were least frequent in the group watching commercials with entertainment chimpanzees. Control questions show that participants did not detect the purpose of the study. These results firmly support the hypothesis that use of entertainment chimpanzees in the popular media negatively distorts the public's perception and hinders chimpanzee conservation efforts.

Link

Early divergence of Khoesan ancestors (Veeramah et al. 2011)

The age estimate is based on microsatellites and a 6 million/25 year generation human-chimpanzee divergence. In general I carry a small basket when it comes to age estimates. Li & Durbin for example, recently estimated that divergence between African farmers and Eurasians began ~100-120ky, a date similar to the date in this paper for the San/non-San split, and even that may be older, depending on whether one uses the genealogical mutation rate from 1000Genomes or a chimp calibration.

The authors of the current paper: "Our estimate for the time of KhoeSan divergence is ~110 kya (95% CI: 52-187 kya)". I think the issue may be further complicated by the potential presence of archaic admixture in Africans, as that may make their effective population size appear larger. On the subject of archaic admixture Michael Hammer (who is a co-author in this one) has another new paper which I will cover in a separate post.

The interesting thing about this paper (aside from the age estimate) is the inference that San diverged first from other humans, rather than a hunter-gatherer first divergence out of which San and Pygmies both branched out. So, it seems that San are really basal to the rest of mankind.

We should not, however, forget that modern human evolution is looking less and less like a tree, with Neandertals, Denisovans, and now archaic African Homo emerging as relevant to our human story, and horizontal admixture in both the sapiens lineage and across Homo species (or should they be subspecies?) is becoming ever more important.

Below is the STRUCTURE analysis from the paper:

Mol Biol Evol (2011) doi: 10.1093/molbev/msr212

An early divergence of KhoeSan ancestors from those of other modern humans is supported by an ABC-based analysis of autosomal re-sequencing data

Krishna R Veeramah et al.

Abstract

Sub-Saharan Africa has consistently been shown to be the most genetically diverse region in the world. Despite the fact that a substantial portion of this variation is partitioned between groups practicing a variety of subsistence strategies and speaking diverse languages, there is currently no consensus on the genetic relationships of sub-Saharan African populations. San (a subgroup of KhoeSan) and many Pygmy groups maintain hunter-gatherer lifestyles and cluster together in autosomal-based analysis while non-Pygmy Niger-Kordofanian speakers (non-Pygmy NKs) predominantly practice agriculture and show substantial genetic homogeneity despite their wide geographic range throughout sub-Saharan Africa. However, KhoeSan, who speak a relatively unique click-based language, have long been thought to be an early branch of anatomically modern humans based on phylogenetic analysis. To formally test models of divergence among the ancestors of modern African populations, we re-sequenced a sample of San, Eastern and Western Pygmies, and non-Pygmy NKs individuals at 40 non-genic (∼2 kb) regions and then analyzed these data within an Approximate Bayesian Computation (ABC) framework. We find substantial support for a model of an early divergence of KhoeSan ancestors from a proto-Pygmy-non-Pygmy NKs group ∼110 thousand years ago over a model incorporating a proto-KhoeSan-Pygmy hunter-gatherer divergence from the ancestors of non-Pygmy NKs. The results of our analyses are consistent with previously identified signals of a strong bottleneck in Mbuti Pygmies and a relatively recent expansion of non-Pygmy NKs. We also develop a number of methodologies that utilize ‘pseudo-observed’ data sets to optimize our ABC-based inference. This approach is likely to prove to be an invaluable tool for demographic inference using genome-wide re-sequencing data.

Link

A good idea for a new project

I was a little disappointed because the excellent new paper by Li and Durbin had not included full genomes from Palaeoafrican individuals, as these are, perhaps, the most interesting ones in terms of the deep ancestry of our species.

I was then reminded, that a full genome of Khoisan individual (KB1) was, in fact, published by Schuster et al. in 2010, and both the paper and the genome are freely available online.

Why is this interesting? Consider the following figure from Schuster et al. (2010):

Notice that the African hunter-gatherer (KB1) has 1,704 private SNPs compared to a Yoruba (NA19240) and Archbishop Desmond Tutu (ABT), and 2,038 SNPs compared to a European American (J. C. Venter), and a Chinese (YH).

This amount of private variation admits to two explanations:

1. Higher effective population size in Khoisan
   
2. Deep population structure followed by admixture

As I have noted in my review of Li & Durbin (2011) UPDATE III, the effective mutation rate is in fact dependent on the effective population size, and it seems almost certain that a lower effective mutation rate must be used in a population of higher effective size.

There is no mystery why this is the case: accumulated genetic variation is a consequence of the mutation rate (how aggressively variation is introduced), and the effective population size (which controls how severely variation is lost due to drift).

A substantial difference in effective population size means that almost certainly the indiscriminate use of a single 2.5x10-8 mutation rate for different human populations is unwise.

This is a serious limitation, as far as I can tell, of the PMSC method introduced by Li & Durbin, as it assumes a single mutation rate parameter which is then used to estimate past population sizes.

In any case, it would be interesting to see how far back the divergence of the Khoisan individual from other humans will be, even if the 2.5x10-8 rate is employed, how large the Khoisan effective population will be, and also what antiquity of population substructure followed by admixture within Africa will be sufficient to "save the phenomena."

Another interesting observation is that the genealogical autosomal mutation rate in humans (1.1x10-8) is actually lower than the estimated evolutionary rate from human-chimpanzee divergence (2.5x10-8)

Nothing in evolutionary biology can account for such a discrepancy, I think, unless there is extreme balancing selection maintaining variation across the entire genome.

So, either:

1. There is a serious flaw in the genealogical rate as estimated from 1000 Genomes trios, or
2. We are about to find out that quite deep population structure and admixture played a role in the history of the genus Homo, deep in a sense of human-ape interbreeding after Homo-Pan speciation 7 million years ago, an idea that was proposed, for different reasons, a few years ago

Calibration of the mutation rate is, of course, quite important for correlating genetic with archaeological events.

For example, Li & Durbin propose that gene flow between Eurasians could have been effected during the Ice Age, as they retreated southwards; such a proposal is necessary to account for divergence between Europeans and East Asians of ~20ky, which is about half the earliest known colonization of Europe. Halving the mutation rate harmonizes the genetic divergence with archaeology, but would push the divergence of Eurasians from West Africans to the dawn of anatomical modernity, and African hunter-gatherer antiquity well beyond it.

I predict that the next few years will reignite many old debates in anthropology.

Autosomal mutation rate from family trios

Razib points me to a new 1000 Genomes Project paper which measures the autosomal mutation directly by looking at trios of individuals (offspring+parents). I don't have much to add except:

1. The authors find substantial family-related variability of the mutation rate. It may be worthwhile to determine whether the mutation rate is a constant across the geographical range of H. sapiens; it is not inconceivable that, if there are family differences in mutability, there may also be population differences.
2. The authors estimate the human-chimp divergence at 7 million years. This is reasonably close to the 6.5 million years in last year's papers about Neandertal/Denisovan admixture in modern years, but it is worthwhile to re-examine all past papers with dates dependent on this calibration point. Until now, we had to "fix" human/chimp divergence, and express divergences within Homo and within Homo sapiens as a fraction of that divergence, but our newfound ability to study whole genomes of 1st degree relatives -and soon many more of those- will make it possible to measure the rate directly and not depend on any calibration based on paleontological data.

Nature Genetics (2011) doi:10.1038/ng.862

Variation in genome-wide mutation rates within and between human families

Donald F Conrad et al.

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline1. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans2, 3. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.

Link

Altruistic adopting forest chimpanzees

PLoS ONE doi:10.1371/journal.pone.0008901

Altruism in Forest Chimpanzees: The Case of Adoption

Christophe Boesch et al.

Abstract

In recent years, extended altruism towards unrelated group members has been proposed to be a unique characteristic of human societies. Support for this proposal seemingly came from experimental studies on captive chimpanzees that showed that individuals were limited in the ways they shared or cooperated with others. This dichotomy between humans and chimpanzees was proposed to indicate an important difference between the two species, and one study concluded that “chimpanzees are indifferent to the welfare of unrelated group members”. In strong contrast with these captive studies, consistent observations of potentially altruistic behaviors in different populations of wild chimpanzees have been reported in such different domains as food sharing, regular use of coalitions, cooperative hunting and border patrolling. This begs the question of what socio-ecological factors favor the evolution of altruism. Here we report 18 cases of adoption, a highly costly behavior, of orphaned youngsters by group members in Taï forest chimpanzees. Half of the adoptions were done by males and remarkably only one of these proved to be the father. Such adoptions by adults can last for years and thus imply extensive care towards the orphans. These observations reveal that, under the appropriate socio-ecologic conditions, chimpanzees do care for the welfare of other unrelated group members and that altruism is more extensive in wild populations than was suggested by captive studies.

Link

Human-chimp Y chromosomes widely divergent

John Hawks covers this important story in detail.

Nature doi:0.1038/nature08700

Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content

Jennifer F. Hughes et al.

The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome1, 2. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis3, 4. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes5, 6, 7, 8, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, ‘genetic hitchhiking’ effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.

Link

Strong apes and fast humans

The paper is freely accessible.

Current Anthropology doi:10.1086/592023

The Strength of Great Apes and the Speed of Humans

Alan Walker

Abstract

Cliff Jolly developed a causal model of human origins in his paper “The Seed‐Eaters,” published in 1970. He was one of the first to attempt this, and the paper has since become a classic. I do not have such grand goals; instead, I seek to understand a major difference between the living great apes and humans. More than 50 years ago, Maynard Smith and Savage (1956) showed that the musculoskeletal systems of mammals can be adapted for strength at one extreme and speed at the other but not both. Great apes are adapted for strength—chimpanzees have been shown to be about four times as strong as fit young humans when normalized for body size. The corresponding speed that human limb systems gain at the expense of power is critical for effective human activities such as running, throwing, and manipulation, including tool making. The fossil record can shed light on when the change from power to speed occurred. I outline a hypothesis that suggests that the difference in muscular performance between the two species is caused by chimpanzees having many fewer small motor units than humans, which leads them, in turn, to contract more muscle fibers earlier in any particular task. I outline a histological test of this hypothesis.

Link