Razib Khan One-stop-shopping for all of my content

April 8, 2012

Another look at mtDNA

The new article in The American Journal of Human Genetics, A “Copernican” Reassessment of the Human Mitochondrial DNA Tree from its Root, is open access, so you should check it out. The discussion gets to the heart of the matter:

Supported by a consensus of many colleagues and after a few years of hesitation, we have reached the conclusion that on the verge of the deep-sequencing revolution…when perhaps tens of thousands of additional complete mtDNA sequences are expected to be generated over the next few years, the principal change we suggest cannot be postponed any longer: an ancestral rather than a “phylogenetically peripheral” and modern mitogenome from Europe should serve as the epicenter of the human mtDNA reference system. Inevitably, the proposed change could raise some temporary inconveniences. For this reason, we provide tables and software to aid data transition.

What we propose is much more than a mere clerical change. We use the Ptolemaian geocentric versus Copernican heliocentric systems as a metaphor. And the metaphor extends further: as the acceptance of the heliocentric system circumvented epicycles in the orbits of planets, switching the mtDNA reference to an ancestral RSRS will end an academically inadmissible conjuncture where virtually all mitochondrial genome ...

January 27, 2012

Out of Africa and out of Siberia

The latest edition of The American Journal of Human Genetics has two papers using “old fashioned” uniparental markers to trace human migration out of Africa and Siberia respectively. I say old fashioned because the peak novelty of these techniques was around 10 years ago, before dense autosomal SNP marker analyses, let alone whole genome sequencing. But mtDNA, passed down the maternal line, and Y chromosomes, passed from father to son, are still useful. Prosaically they’re useful because the data sets are now so large for these sets of markers after nearly 20 years of surveying populations. More technically because these two regions of the genome do not recombine they lend themselves to excellent representation as a tree phylogeny. Finally, mtDNA in particular is particularly amenable to estimates via molecular clock methodologies (it has a region with a higher mutational rate, so you can sample a larger range of variation over a given number of base pairs; you can use STRs, which mutate rapidly, for Y chromosomes, but there seems to be a lot of controversy in dating).

The papers are The Arabian Cradle: Mitochondrial Relicts of the First Steps along the Southern Route out of Africa and Mitochondrial DNA and Y Chromosome Variation Provides Evidence for a Recent Common Ancestry between Native Americans and Indigenous Altaians. Dienekes has already commented on the first paper. I am not going to take a detailed position on either, but I have to add that we need to be very careful of extrapolating from maternal or paternal lineages, and, assuming that population turn over is low enough that we can make phylogeographic inferences about the past from the present. For example, if you look at mtDNA South Asians as a whole strongly cluster with East Asians and not Europeans, while if you look at Y chromosomes you see the reverse. The whole genome gives a more mixed picture. Additionally, ancient DNA analyses in Northern Eurasia are showing strong discontinuities between past and present populations. So coalescence back to last common ancestor between two different lineages in two different regions may actually be due to diversity in a common source population more recently, which entered into demographic expansion and replaced other groups.

If you need the papers, email me. Some of you know the alphabet soup of haplogroups better than I do. Below are two figures which I think give the top line results.

June 28, 2011

“What if you’re wrong” – haplogroup J

Back when this sort of thing was cutting edge mtDNA haplogroup J was a pretty big deal. This was the haplogroup often associated with the demic diffusion of Middle Eastern farmers into Europe. This was the “Jasmine” clade in Seven Daughters of Eve. A new paper in PLoS ONE makes an audacious claim: that J is not a lineage which underwent recent demographic expansion, but rather one which has been subject to a specific set of evolutionary dynamics which have skewed the interpretations due to a false “molecular clock” assumption. By this assumption, I mean that mtDNA, which is passed down in an unbroken chain from mother to daughter, is by and large neutral to forces like natural selection and subject to a constant mutational rate which can serve as a calibration clock to the last common ancestor between two different lineages. Additionally, mtDNA has a high mutational rate, so it accumulates lots of variation to sample, and, it is copious, so easy to extract. What’s not to like?

First, the paper, Mutation Rate Switch inside Eurasian Mitochondrial Haplogroups: Impact of Selection and Consequences for Dating Settlement in Europe:

R-lineage mitochondrial DNA represents over 90% of the European ...

June 10, 2011

Man at Bab el-Mandeb

ResearchBlogging.orgIn light of my last post I had to take note when Dienekes today pointed to this new paper in the American Journal of Physical Anthropology, Population history of the Red Sea—genetic exchanges between the Arabian Peninsula and East Africa signaled in the mitochondrial DNA HV1 haplogroup. The authors looked at the relationship of mitochondrial genomes, with a particular emphasis upon Yemen and the Horn of Africa. This sort of genetic data is useful because these mtDNA lineages are passed from mother to daughter to daughter to daughter, and so forth, and are not subject to the confounding effects of recombination. They present the opportunity to generate nice clear trees based on distinct mutational “steps” which define ancestral to descendant relationships. Additionally, using neutral assumptions mtDNA allows one to utilize molecular clock methods to infer the time until the last common ancestor of any two given lineages relatively easily. This is useful when you want to know when a mtDNA haplgroup underwent an expansion at some point in the past (and therefore presumably can serve as a maker for the people who carried those lineages and their past ...

April 27, 2011

Neandertal hybridization & Haldane’s rule

Mr. James Winters at A Replicated Typo pointed me to a short hypothesis paper, Neanderthal-human Hybrids. This paper argues that selective mating of Neandertal males with females of human populations which had left Africa more recently, combined with Haldane’s rule, explains three facts:

- The lack of Neandertal Y chromosomal lineages in modern humans.

- The lack of Neandertal mtDNA lineages in modern humans.

- The probable existence of Neandertal autosomal ancestry in modern humans.

If you don’t know, Haldane’s rule basically suggests that there’s going to be some sort of breakdown in the heterogametic sex. In humans females are homogametic, XX, and males are heterogametic, XY. The breakdown need not be death (or spontaneous abortion). It could be sterility (e.g., some mutation or genetic incompatibility which results in the malfunctioning of the flagella of sperm would do it).

So you have a scenario where only Neandertal males are interbreeding with the intrusive groups from the south. The hybrids from these pairings would then lack Neandertal mtDNA, since mtDNA is passed only from mothers. But the male offspring would have Neandertal Y chromosomes. This is where Haldane’s rule kicks in: these males in their turn would not reproduce. Therefore only the female hybrids ...

November 17, 2010

Icelanders descended from Native Americans?

ResearchBlogging.orgThat is the question, and tentatively answered in the affirmative according to a new paper in The American Journal of Physical Anthropology. A new subclade of mtDNA haplogroup C1 found in icelanders: Evidence of pre-columbian contact?:

Although most mtDNA lineages observed in contemporary Icelanders can be traced to neighboring populations in the British Isles and Scandinavia, one may have a more distant origin. This lineage belongs to haplogroup C1, one of a handful that was involved in the settlement of the Americas around 14,000 years ago. Contrary to an initial assumption that this lineage was a recent arrival, preliminary genealogical analyses revealed that the C1 lineage was present in the Icelandic mtDNA pool at least 300 years ago. This raised the intriguing possibility that the Icelandic C1 lineage could be traced to Viking voyages to the Americas that commenced in the 10th century. In an attempt to shed further light on the entry date of the C1 lineage into the Icelandic mtDNA pool and its geographical origin, we used the deCODE Genetics genealogical database to identify additional matrilineal ancestors that carry the C1 lineage and then sequenced the complete mtDNA genome of 11 contemporary C1 carriers from four different matrilines. Our results indicate a latest possible arrival date in Iceland of just prior to 1700 and a likely arrival date centuries earlier. Most surprisingly, we demonstrate that the Icelandic C1 lineage does not belong to any of the four known Native American (C1b, C1c, and C1d) or Asian (C1a) subclades of haplogroup C1. Rather, it is presently the only known member of a new subclade, C1e. While a Native American origin seems most likely for C1e, an Asian or European origin cannot be ruled out.

The core of the article treads the confusing gray zone between rock-hard precise science and the more vague and intuitive truths of history. One the rock-hard part, there is a huge literature on maternal genetic lineages, the mtDNA. Because this genetic material is copious it was some of the first to be analyzed using molecular clock models. A molecular clock is a feasible with mtDNA because it is haploid; it is only inherited through females and so is not subject to recombination which might break apart associations of distinctive genetic markers. Instead of being a reticulated mesh the genealogy of mtDNA is a clean and inverted elegant tree leading back to a common ancestress. You are finding the line of your mother’s mother’s mother’s mother’s….

But synthesizing this clarity with human history is more difficult, because we are dependent on the bias of text, and even more tendentious clues from oral history and archaeology. Because of Iceland’s Lutheran Christian heritage the maternal lineage here could be traced back to 1700. This does not mean that the first woman in the line that we know of was born like Athena from the head of her father; rather, the records were not kept well enough to continue unbroken back to the medieval era. We do know that the first permanent Norse settler in Iceland arrived in 874, and, that very few immigrants from Scandinavia added diversity to the gene pool after ~1000. Iceland is a small and poor island, so quickly reached its Malthusian maximum. How else to explain that Icelanders made a secondary migration to Greenland?

The most obvious explanation for the existence of the subclade of the C1 lineage is that it arrived recently. Without knowing anything else that is what you’d have assumed. But as noted above the individuals who carry it have been traced back to a common ancestor in the early 18th century; these are native Icelanders, at least if native means anything substantive. An second point which rejects recent injection of this lineage into the gene pool: the Icelanders are their own special branch of C1, C1e. The phylogenetic tree of C1 below illustrates the  relationship of the branches to each other. Since the font is so small, I added in clarifying labels (from top to bottom it’s C1a to C1e, with further clades such as C1d1):


As you can see, this is mostly an Amerindian clade, with some some Asians. But, by surveying the public data they did find two individuals who were European who carried possible C1e. I’ll quote:

…, using the criteria of one mutational difference from C1e when sequences were avail- able for only hypervariable segment 1 (HVS1) or 2 (HVS2) and two mutational differences when both HVS1 and HVS2 sequences were available. The result was a shortlist of 276 sequences that we suggest be checked first for C1e coding region mutations (Supp. Info. Table S3). We note that for the sequences for which geographical information is available, all but two were sampled from individuals with Native American ancestry—i.e. from the Canary Islands and Germany.

The German sequence…represents a perfect match to the Icelandic C1e for the short HVS1 fragment spanning sites 16024–16365. This raises the intriguing, but perhaps unlikely, hypothesis that C1e is a European-specific subclade of C1, following the precedent of the European and Native American subclades of mtDNA haplogroup X2…However, given the dense sampling of mtDNA variation in European populations, it is clear that C1e is exceedingly rare, a fact that weighs against a hypothesis of antiquity in Europe.

They believe that the Canary Islander is probably the result of admixture during the Spanish colonial era with someone who returned from the New World colonies.  The German is the one to focus on. A plausible alternative model is that C1e is a very low frequency European lineage, which increased in frequency in Iceland simply through genetic drift because of that island’s small population. Remember that though C1e is rare in Iceland, its frequency is much higher than in Northern Europe as a whole. Though here we must be cautious because the typing was preliminary in the Germany case, the authors note that “This is because there are no other known human mtDNA sequences belong to C1e out of the 6747 complete sequences available in the literature.” Also, the authors observe that there is variation among the Iceland C1e lineages, mutations which differentiate them. This further tilts the playing field toward an early entrance of the lineage into Iceland, probably before Columbus, because a late arrival would not have had time to build up mutational variation in the region of Iceland where C1e is found.

572px-Bjork_and_the_Swan_DressAs this subclade is absent among Native Americans, you may wonder as to a relationship to Greelanders or Inuit. The larger C1 haplogroup as a whole is not evident in these populations. You can inspect the geographical distribution closer yourself. If this woman was a non-European, she was not maternally related to the peoples who replaced the Norse in Greenland. Though we should also be careful about assuming that the present genetic variation in the American Arctic is representative of pre-modern variation.

If the Greenland and ancient European hypotheses are rejected, what we have is a woman who entered the Icelandic society from an extinct lineage of Native Americans, probably from the northeast (or perhaps her Greenland Norse mother was of this line). What the Norse would have termed Markland. It is tempting to point to the Norse settlement at L’Anse aux Meadows in Newfoundland. Perhaps the Europeans had enslaved a native woman, and taken her back to their homeland when they decamped? But more likely to me is the probability that the Norse brought back more than lumber from Markland, since their voyages spanned centuries.

Finally, does this explain Bjork? I doubt it. A minority of Scandinavians, especially ones of Sami background, exhibit an “Asiatic” cast to their features. The autosomal genomic content of the Icelanders is what you’d expect, Scandinavian leavened with British, and twisted with their own particular history of population bottlenecks. Only the precision of mtDNA typing brought the reality of the woman who carried C1e into the light. In terms of total genome content she is one of tens of thousands of ancestors to any given descendant, and she may be one of the less common ones in the family trees because of her likely lower status. Though the flip side of the nature of mtDNA, and the inbred aspect of the Iceland pedigree, is that probably all native Icelanders can draw many lines of descent to this woman.

Citation: Ebenesersdóttir SS, Sigurðsson A, Sánchez-Quinto F, Lalueza-Fox C, Stefánsson K, & Helgason A (2010). A new subclade of mtDNA haplogroup C1 found in icelanders: Evidence of pre-columbian contact? American journal of physical anthropology PMID: 21069749

Image Credit: Cristiano Del Riccio

March 27, 2010

The Mysterious Other

Last week Nature published a paper which may have found a new ‘branch’ of the hominin evolutionary bush which may have been coexistent which modern humans and Neandertals. I recommend The Atavism, Carl and John Hawks on this story. Interesting times.

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