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Friday, September 3, 2010

Bonobo mtDNA... and some human implications.


Researchers from the University of Bonn have published a new paper on Bonobo mitochondrial genetics:


Gabor Zsurka et al., Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and humans. BMC Evolutionary Biology. Open access.

Background

We have analyzed the complete mitochondrial genomes of 22 Pan paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens.


Results


We identified three major clades among bonobos that separated approximately 540,000 years ago, as suggested by Bayesian analysis. Incidentally, we discovered that the current reference sequence for bonobo likely is a hybrid of the mitochondrial genomes of two distant individuals. When comparing spectra of polymorphic mtDNA sites in bonobos and humans, we observed two major differences: (i) Of all 31 bonobo mtDNA homoplasies, i.e. nucleotide changes that occurred independently on separate branches of the phylogenetic tree, 13 were not homoplasic in humans. This indicates that at least a part of the unstable sites of the mitochondrial genome is species-specific and difficult to be explained on the basis of a mutational hotspot concept. (ii) A comparison of the ratios of non-synonymous to synonymous changes (dN/dS) among polymorphic positions in bonobos and in 4902 Homo sapiens mitochondrial genomes revealed a remarkable difference in the strength of purifying selection in the mitochondrial genes of the F0F1-ATPase complex. While in bonobos this complex showed a similar low value as complexes I and IV, human haplogroups displayed 2.2 to 7.6 times increased dN/dS ratios when compared to bonobos.


Conclusions


Some variants of mitochondrially encoded subunits of the ATPase complex in humans very likely decrease the efficiency of energy conversion leading to production of extra heat. Thus, we hypothesize that the species-specific release of evolutionary Background We have analyzed the complete mitochondrial genomes of 22 Pan paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens.



Pan genus mtDNA phylogeny (fig. 1)
PanTrog = Pan troglodytes (chimpanzee), PP = Pan paniscus (bonobo)

It is very apparent that bonobos have three major mtDNA haplogroups, named A, B and C.

Unlike humans (or at a lesser extent common chimpanzees), bonobos live in a well defined area of the SW Congo basin, limited by rivers, and have therefore never experienced a expansion since they became separated from their chimpanzee cousins. This makes them a good reference to better understand how demographic expansion affected our genetics, specifically our mtDNA.


Chronology

The authors say that the most recent common ancestor (MRCA) of all bonobos (by mtDNA) lived some 540,000 years ago (430-670 Ka. with 95% confidence interval).

If the graph above has a scale (and I understand it does) and assuming this estimate is correct, then the divergence of both Pan species happened c. 2.1 million years ago (1.7-2.6 Ma at 95% CI) - using simple linear maths.

Notice that Caswell 2008 already suggested a possible divergence age of 1.5-2.0 Ma in order to make it coincident with the formation of the Congo basin as we know it, a geological phenomenon that was surely itself the cause of the chimp-bonobo divergence. In my own words back then:

That the chimpanzee-bonobo split should be move backwards in time to at least 1.29 million years ago. And, that if the human-chimp divergence age is actually older (8 million years instead of 7), then this event would be coincident with the formation of the Congo river (1.5-2 Myrs BP), that many people belive is at the origin of bonobo speciation.

So I think we can confirm that the Pan paniscus speciation event happened most likely some 2 million years ago, when some undifferentiated Pan became isolated from the rest in the SW Congo basin on purely geological reasons.

It is also said that:

The maximal nucleotide difference between bonobo groups is, however, 1.5 times higher than in humans, and thus somewhat closer to the distance between modern humans and the extinct Neandertal.


While this affirmation is unspecific on the details, it seems to weight against the shortest claimed divergence ages for the two big-headed human species.


Bonobo reference sequence is a mix

The authors find that the bonobo reference sequence (GeneBank) seems to be not a genuine one but a mix of two rather unrelated ones. Hence they propose deprecating the extant reference and use the closest one of theirs, PP23, as new reference.


Purifying selection

The authors find strong support for purifying selection in both bonobos and humans. However some of this funtional constraint seems to have been lifted for some groups when humans spread around the world, specially to colder locations. Therefore they suspect it related to the metabolic determinants of high tropical temperatures. However some of this constraint may have been already lifted still in Africa as the branch leading to humans evolved hairlessness and sweat.

For ATPase, the nonsynonymous/synonymous (dN/ds) ratio is lowest among the Khoisan (haplogroups L0 and L1 essentially) and highest in haplogroup A. However other Siberian/Native American haplogroups (C and D) do not show anything so extreme, so rather than thinking in terms of positive selection, the authors argue that it is loss of evolutionary constraint what we see here:

Therefore, we conclude, in agreement with others [16], that the observed increase of dN/dS values for the mitochondrial ATPase genes in humans cannot be interpreted in favor of positive selection at colder climate conditions, but rather is the result of the release of strong evolutionary constraints during population expansion and migration of modern humans.

Another interesting finding is surely that one of the three bonobo haplogroups displays a mutation at locus 8344A>G, which is strongly implicated in MERRF syndrome (a mildly incapacitating degenerative disease) in humans. However they suspect that a nearby bonobo-specific mutation, present in all bonobo mtDNA, may be acting to prevent this effect in bonobos.

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