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Thursday, August 7, 2014

Tuberculosis and the early peopling of America


Mycobacterium tuberculosis is a mycobacteria that infects different hosts, and one of them is us, humans. The M. tuberculosis sensu stricto is found among people all around the world. The bacillus that causes tuberculosis (TB) infects its host and may remain for a long period of time in a latent state where the host's immune system contains the infection yet is unable to eliminate the bacterium. About 33% of humans carry TB in this latent state. It only attains higher virulence under certain conditions.


Its specificity regarding our species implies that we have very long relationship with M. tuberculosis; it was transmitted from one person to another, ususlly within family settings, and therefore dispersed across the globe with our social group migrations. Its dispersal reflects the march of humans across the globe. In fact there are several genetic families of human M. tuberculosis and they have specific geographical locations. It also infects other mammals (cows, goats, seals, etc.) and they have been suggested as the original source for the human strain of TB.


TB poster

As usual, in my quest for proof on an early peopling of America (by H. erectus or Neanderthal), I am always attracted by odd gradients in the distribution of genetic traits. The bacteria that causes TB has some peculiarities in its global distribution and mutations. Today's post looks into this.


The Beijing TB genotype


A paper Mokrousov et al., 2005 [1] studied the origin and dispersal of TB. They chose the Beijing strain of the bacteria and in their analysis detected another variant (bold is mine): " a low-endemic type in the United States, the N-branch has no IS6110 insertion in NTF region. Sequencing of the NTF region in N-branch demonstrated that it is intact; that is, it has never harbored IS6110 insertions. In our opinion, this implies that N-branch presents the most ancient or “primordial” group that was isolated from the rest of the Beijing strains at the very beginning of its evolution" [1].


So here it is, a strain unique to the Americas, where it is found at a low-endemicity and which seems to be older than the widespread Eurasian Beijing line.


But what to the authors make out of this? Not what I expected; they disregard a possible American origin for this line of TB and strongly support an Asian origin for it (My comments are Bold) : [1]


"We sought to define a human host population in which the most recent common ancestor of the Beijing primordial N-branch (currently, endemic North American) and the ancient MIRU types MT11 and MT2 (radiating through a presumably Chinese primary expansion) appeared.
If the Amerindian endemic N-branch is "primordial", then it is in my opinion, a line that appeared in American and spread from there outwards.
This most recent ancestor could not be in the initial group of humans migrating from Africa, nor it could be in next step Levantine populations since this genotype is not endemic in Africa as a whole or in the Middle East and Europe (Bifani et al. 2002; Glynn et al. 2002).
Being absent in Africa and the Middle East makes me wonder if it may be even more ancient than modern humans, for instance a strain in H. erectus, who left Africa 1.8 Mya. They probably evolved this branch far away from the Middle East and African populations, taking it to America. Alternatively we can imagine a Neanderthal population in America as its source.
It could not have arisen in China (east Asia), since Chinese isolates already had one IS6110 insertion in the NTF locus (Bifani et al. 2002) and presented a second step in the Beijing evolution. It seems unlikely that the North American N-branch (i.e., initial Beijing variant) emerged in situ, since we can hardly imagine any significant human gene flow from there to east Asia or Eurasia as a whole.
Once again the "prejudice" against an "Out of America" theory. The paper dismisses the possibility that H. erectus or even Neanderthal had reached America early carrying a M.Tuberculosis strain, } evolved there and later back-flowed to Asia.
Rather, the low-level endemicity of the most ancient Beijing N-branch in North America demonstrates that it was brought to this continent from Eurasia with a small human group, an event that corresponds to the first entry of humans to this continent.
Or does it reflect an ancient archaic origin, that prevails until now, having infected the more recent arrivals (Homo sapiens) as the archaic ones admixed with them?


Of course Mokrousov et al., 2005 [1] adopt the mainstream point of view and propose a late entry of the "archaic" lineage into America:


  • The Beijing genotype first appeared in humans with K-M9 Y chromosome haplogroup in central Asia.
  • This population later split in humans into other groups that entered Siberia and East Asia. Y chromosome hg. P -M45 marched northeast (20 - 30 kya) with the ancestral Beijing strain (intact NTF).
  • The strain reached Beringia entering America some 17 - 20 kya.
  • The initial peopling bottleneck and the post-discovery decimation of the population produced the current low-endemicity of this archaic strain.

Interestingly, [1] "two N-branch strains with intact NTF region were found in our collection of Russian Beijing strains and that Beijing strains, defined as ancestral by other markers, have previously been described, although as low-endemic, in modern Russia and the United States [...] Thus, they may represent relic strains left on the first passage of the Beijing primordial sublineage (intact NTF) through Siberia to North America 20,000-30,000 yr ago."[1]


Once again, things could be the other way round: the Russian strain with intact NTF region (i.e. the ancestral version) may be a back-migration Out of America and into Siberia of the archaic American strain. Actually the sequence mentioned above could have taken place earlier, with Neanderthals or H. erectus as the vectors from Africa into America.


The American variety of TB


A more recent paper (Hershberg et al., 2008) [2] did an in-depth analysis and sequencing of M. tuberculosis genome, and revealed that the different TB strains were more genetically diverse originally imagined. The image below (from [2]) shows the lineages of TB found around the world. The paper suggests that the "purple" colored strain reflects the initial Out of Africa migration to Australia, along the coast of the Indian Ocean (it may reflect in my opinion, the OoA move of H. erectus), and suggests a dispersal mode for the other strains:


TB strains tree
Strains of TB bacteria. From [2]

This paper places the West African, "rim of Indian Ocean" and Philippines strains grouped together with some "animal" lineages and classifies them as "Ancient". The other strains: European-American, East African and East Asian are grouped together as "Modern". But this is biased due to how it considers the American line:


Unfortunately the paper [2] ignores the ancestral Amerindian strains mentioned in [1] and focuses on the orthodox Out of Africa dispersal and a recent post-Columbian entry of TB into America (the red colored strains in the image above): "...the presence of Euro-American (red) strains on the American continent can be explained in terms of the exodus from the over-populated European cities to America at the end of the 19th century—a 'vast movement that dwarfed all earlier migrations'" [2].


I find it very probable that the TB strains carried by Europeans to America found a fertile territory in which to expand, and it did so, almost obliterating the endemic local strain found among Amerindians.


But, this obliteration began much earlier than the nineteenth century. It started during the initial discovery period (1500s), when the European TB strain reached Ameica. It had a different evolutionary trajectory and a greater virulence compared to the local Amerindian strain. This surely caused a rapid progression from latent to active disease and death among Native Americans, replacing the original ancestral strain. This is seen nowadays in Africa where imported modern strains overtake the ancient local ones. [2]


The horrendous bursts of tuberculosis among Native American were not due to the Americas being devoid of the illnes. On the contrary, "different pathogenic strains of the bacteria, the absence of long or permanent immunity and, of course, the socio-cultural determinants" were factors which led to a prevalence of the European variety of the disease. [5]


TB in Pre-Columbian America


Surprisingly, as I mentioned above, the local endemic Amerindian TB line is completely ignored in many studies. Yet TB was a widespread disease in prehistoric America and many papers have been written on the subject. Below I will detail some findings and cite some scholarly bibliography, merely as a reference:


I. South America


The most ancient case in the New World comes from the South American Paracas-Caverna culture (Peru), dated to ca. 160 BCE (2,150 ya). [5]


Peru and Northern Chile are ideal sites for detecting TB: The dry climate of that region has contributed to preserve thousands of mummies, which have been analyzed for TB cases. A sample of about 1,000 mummies from this area were autopsied and yielded Five (5) "clear cases of Pott's disease" [3]. This allows the calculation of "the estimated pre-Columbian tuberculosis prevalence on the sample [of] between 10 and 25%." [3]. This is a "pandemic level" for the disease ca. 900 C.E.


The paper suggests some back-flow of Amerindian TB to Europe after the 1492 Discovery period. [3]


Even the Chachapoya mummies prove the existence of TB in that region: prevalence of pulmonary TB among them "might have been as high as 25%". [6]


Argentina [4] also has ancient examples of TB: At Santa María, Catamarca province where "six individuals out of seventy so far excavated provided evidence of the existence of the disease in the Santa Maria Valley between the end of the Late Ceramic Period and the onset of the expansion of the Inca Empire [1310 to 1480 C.E.] [4]


Patagonia has also provided remains of a person with TB from Salitroso Lake, Santa Cruz dated 728 BP, but it is still disputed. [4]


II. North America


In North America it has been detected in human remains from the U.S. Central Plains and Lake Ontario, Canda and are younger than the South American samples. [5]


Summarizing, tuberculosis has existed in America for thousands of years and only when conditions favored it, did it become epidemical. Mostly it occured as a low endemic disease. [5] There is a bias towards mummified samples because those remains are better preserved than others, and these are mostly from the coastal areas of the Peruvian and Chilean region, so the disease may have been much more widespread than imagined, but is yet undetected.


The relatively recent dates (post 1,000 C.E.) for North American TB may be due to contact with Vikings in the 1400s who could have spread the disease to America [5], it is therefore possible that North and South American natives had different "different epidemiological histories for tuberculosis" where one is Viking originated and the other dates back to the initial peopling of the Continent. [5]


As can be expected, the scarcity of complete human remains and a disease which even under pandemic conditions only infects between 10 and 25% of the population, makes it pretty unlikely to find TB in the bones of Paleoindians or other prehistoric populations. We should not suppose that it is recent because the oldest bones with TB are only 2,000 years old. This is actually not the case.


Homo erectus and TB


A paper by Kappelman et al., (2007) reported finding evidence of TB in a 490 - 510 ky old Homo erectus specimen found in the town of Kacabas, western Turkey.


But was this strain one of those found nowadays? or is it ancestral to modern human TB lineages?


The different Mycobacterium tuberculosis complex (MTBC) agents infect a wide range of mammals, for example: M. bovis, (cows), M. pinnipedii (seals), and M. caprae (goats). However these and the human M. tuberculosis are very similar. These TB bacteria like the syphilis bacteria are clonal, and have very little genetic exchange among them. Their synoymous nucleotide variation is less than 1 in 5,000. Small indeed! So it is very likely that the H. erectus variety of TB microbe be the "ancient" root mentioned as endemic in the Americas and ancestral to the Beijing strain.


Unfortunately there are no other papers reporting TB in Neanderthals or other hominins, so we cannot be certain of its ancient distribution range or its prevalence among archaic humans.


Closing comments


The sequencing of the genome of the native American strain of TB will surely show that it does not share its root with the European clade. however the Amerindian strain is rare and surely overlooked in the samplings that have been carried out. Perhaps recovery of M. tuberculosis from ancient remains may provide evidence of its singular origin. We will have to wait for additional studies to prove or discard the possibility that Homo erectus or Neanderthals reached America with the ancient TB bacteria which evolved there into the Amerindian strain and back-migrated to Asia to continue evolving there.


Sources


[1] Igor Mokrousov, et al., (2005). Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography. Genome Res. Oct 2005; 15(10): 1357–1364. doi: 10.1101/gr.3840605
[2] Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, et al., (2008). High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography. PLoS Biol 6(12): e311. doi:10.1371/journal.pbio.0060311
[3] Guido P. Lombardi and Uriel Garcia Caceres, (2000). Multisystemic tuberculosis in a Pre-Columbian Peruvian mummy: four diagnostic levels, and a paleoepidemoloigical hypothesis. Chungara, Revista de Antropologia Chilena Volumen 32, N° 1, 2000. pp. 55-60
[4] Mario A. Arrieta, Maria de la Asuncion Bordach and Osvaldo J. Mendonca, (2011). Tuberculosis precolombina en el noroeste argentino (NOA). El cementerio de Rincon Chico 21 (RCH 21), Santa Maria, Catamarca . Intersecciones antropol. vol.12 no.2 Olavarria jul./dic. 2011
[5] Jordi Gómez, Prat, Sheila MF and Mendonça de Souza, (2011). Prehistoric tuberculosis in America: adding comments to a literature review. Mem. Inst. Oswaldo Cruz vol.98 suppl.1 Rio de Janeiro Jan. 2003 http://dx.doi.org/10.1590/S0074-02762003000900023
[6] Gerald Conlogue, (2002). More TB in Peruvian Mummies . Archaeology Volume 55 Number 2, March-April 2002
[7] Kappelman J, Alcicek MC, Kazanci N, Schultz M, Ö:zkul M, Sen S., (2007). First Homo erectus from Turkey and implications for migrations into temperate Eurasia. Am J Phys Anthropol (in press) doi:10.1002/ajpa.20739



Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall © 

8 comments:

  1. Great find of the N strain endemic to the Americas! I of course appreciate your unbiased conclusion: "Once again the "prejudice" against an "Out of America" theory. The paper dismisses the possibility that H. erectus or even Neanderthal had reached America early carrying a M.Tuberculosis strain, } evolved there and later back-flowed to Asia."

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  2. What do you think of it, Austin?
    http://dienekes.blogspot.com.br/2014/08/tuberculosis-is-6000-years-old.html

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    1. I was pleasently surprised and I am writing a post on it.
      The theory is good but the best explanation is not that Africans passed a TB strain to seals, where it mutated and then infected Amerindians.
      The Amerindian strain is closer to the root than the seal branch!
      Yet is so different from African TB that it is on its own branch.
      The sequence in my opinion is: H. erectus had TB this evolved in the Old World and in the New World. The New World strain infected seals. And evolved into the current Amerindian strain. It is so different from the Eurasian-African ones because it evolved in solitude in America.

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    2. What makes you think that mixing with Erectus or Neanderthal occured instead of Amerindians themselves being their descedents in a sense they especiated in here? I see continuity between the mongoloid phenotype and homo erectus and even Neanderthal eye-sockets and probably very coarse hair. There isn't actual proof of an asian origin of natives, but the opposite.

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    3. I am still undecided about the issue, so I am playing with different ideas while I continue studying the matter. There is a very close similarity between al human beings, we are indeed a complex admixture of our predecessors. Which these actually are and where the admixture took place will be unveiled as DNA sequencing advances.

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    4. I don't think that the people making those studies are interested in truth. More like wishfull thinking, political motivations and perhaps even racism against the natives.

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    5. Anon: the data says what the data says, and paper offers one possible interpretation (that seals brought TB over from Africa). Why do you think this is wishful thinking or anti-aboriginal political motives? The paper says that the bone samples that were used were obtained with permission from modern aboriginal groups in America.

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  3. http://patagoniamonsters.blogspot.com.ar/2014/08/on-tb-seals-and-early-peopling-of.html

    I posted a continuation of this post today, August 26. It deals with a recent paper which posits that TB appeared in Africa only 6,000 years ago. But, it recognizes how different Amerindian TB is from the other human strains, soemething that I mentioned in this post above.

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