Helicobacter pylori and the Out of Africa theory

A paper published in Science (F. Maixner, 2016 [1]) reported that they studied the DNA of the Helicobacter pylori recovered from Ötzi, the iceman, whose mummified body was discovered in an Alpine glacier melt in 1991. They body is 5,300 years old and they expected to find the typical European variety of H. pylori in the remains of his stomach. Instead they found the Asian variety. Casting a shadow on the current Out of Africa theory of the peopling of Europe.

Their abstract says: (bold is mine) "The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H. pylori is known to be a hybrid between Asian and African bacteria, but there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans. Here, we present a 5300-year-old H. pylori genome from a European Copper Age glacier mummy. The “Iceman” H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years."

I wrote about this some time ago, that the different H. pylori variants are not necessary of an African origin. These findinngs by Maixner and his team seem to support this idea.

According to the paper (it is free access), the Iceman's variant of H.pylori is closer to the South Asian one! (India, Malaysia, Bangladesh, Thailand, Philippines) and is furthest from the N.E. Africa and W. Africa variant (from Nigeria to Ethiopia)... See this graph with the different variants and Ötzi's position closest to Asian types.

So this is no man from the steppes or a Middle Eastern H. pylori variant. This copper age man has a H. pylori found in SE Asia. The route taken by humans out of Africa, and long before them, by Homo erectus to... South East Asia. Are we seeing some signal of an old variant of H. pylori here? One that predates European H. pylori and also the African one?

What is odd is that a paper by A. Keller et al., (2012) [2] found the Iceman was closely related to the population of the two islands of Corsica and Sardinia in the NW Mediterranean Sea: "Sequence analysis showed genetic distance from modern mainland European populations, but proximity to the extant populations of Sardinia. Interestingly, the Iceman's Y-haplogroup G2a4 has hitherto only been found at appreciable frequencies in Mediterranean islands of the Tyrrhenian Sea (Sardinia and Corsica). Although admixture and demographic history cannot be reconstructed from one individual alone, the Iceman's Y-chromosomal data document the presence of haplogroup G in Italy by the end of the Neolithic and lends further support to the demic diffusion model. The affinity of the Iceman's genome to modern Sardinian groups may reflect relatively recent common ancestry between the ancient Sardinian and Alpine populations, possibly due to the diffusion of Neolithic peoples." [2]

What do Sardinians and South Asians have in Common? Perhaps Keller et al. are right and it just reflects a group that survived from the days of Ötzi in isolation in those two islands, and ths same DNA is found at very low levels (less than 1%) across Europe.

The paper states that: "Furthermore, our co-ancestry results indicate that the Iceman’s strain belonged to a prehistoric European branch of hpAsia2 that is different from the modern hpAsia2 population from northern India" [1]. Which is very interesting. It is a really ancestral branch. (Neanderthal ?)

Figure 4 in the paper shows the tree, with two big branches, one is N.E.Asia and America, the other has Africa, Europe, South Asia and Oceania. That is indeed striking.

The First branch, splits into Africa and Europe, and another which holds the Iceman and also includes to India, Papua New Guinea and Sahul.

The other main branch with N. E. Asians (Korea, China and Japan) also hash the Amerindians (Peru: Puno and Cuzco variants and Venezuela) with many smaller branches. Does that imply a longer time for their diversification vs. the other human groups?

The best part is that over the last few months a series of discoveries have cast some doubt on the Out Of Africa theory: Neanderthal backflow into Africa, and the 80- 120 kya old teeth found in China. What new findings will 2016 bring with it?

Source

[1] Frank Maixner, et al., 8 January 2016: The 5300-year-old Helicobacter pylori genome of the Iceman Vol. 351 no. 6269 pp. 162-165 DOI: 10.1126/science.aad2545
[2] A Keller et al. (2012) New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing, Nature Communications 3, Article number: 698 doi:10.1038/ncomms1701

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2016 by Austin Whittall © 

Helicobacter Pylori and Homo Erectus

I am posting once again on the Helicobacter Pylori bacteria, because I came across a paper while researching on Homo erectus in Southern Asia for my recent series on Y chromosome C haplogroup.

My previous post in case you are interested is this one: Ulcer causing bacteria and Neanderthals in America.

H. Pylori and Homo erectus

H. pylori are a type of bacteria that is found in the stomachs of roughly 66% of mankind. Its name "helicobacter", comes from its shape ("Helico" means "spiral").

People usually pick it up during childhood and in general it lives in its host unnoticed but, in certain people it causes disease (ulcers, inflamation or gastritis and in some cases, cancer).

It spreads from one person's mouth to another, so it quickly passes from parents to children and is exchanged between siblings as well as between couples. Another form of transmission is through contact with feces due to lack of hygene (a person who does not wash his or her hands after using the toilet). It can also be picked up from contaminated water or food.

Risk is higher in developing countries, but in the past, overcrowded conditions, lack of access to clean water and poor hygene allowed for an ample transmission within geographic localities and the people inhabiting them.

For this reason, it spreads rapidly within a population and is also affected by natural selection however this does not completely erase its origin.

Comment on Natural Selection.
The original American variety of H. pylori (known as hspAmerind) was specialised in infecting Native American hosts, when Europeans arrived (1492), the dramatic drop in native population due to war and disease plus the increase of Europeans and their "mestizo" mixed Amerind-European offspring allowed the more generalised European H. pylori (hspEurope) to outcompete it and greatly replace it.

This familial transmission keeps the different varieties of H. pylori within certain social groups (obviously those who live, share food, toilets, water and have sex together). This allows it to be used to study the prehistoric migrations of human beings with H. pylori in their stomachs.

Our most distant ancestors carried it in their gut, and as H. habilis evolved into our archaic ancestors (Neanderthals, H. erectus, H. heidelbergensis, etc.), H. pylori was in their stomachs, evolving too and passing along the evolving line of hominins till it reached us and (as orthodoxy states), left Africa some 60 kya in the wave of H. sapiens that would people the world and replace any other hominins out there. These human migrants settled in different regions and their H. pylori also evolved separately from those in the bellies of other humans in other places.

This is attested by the fact that there are different varieties of the bacteria specific to different geographic locations: [1]

• hpNEAfrica, from Northeast Africa.
• hpAfrica1, found in Western and Southern Africa.
• hpAfrica2, only found in South Africa.
• hpEurope, found in Europe, Western Asia, the Middle East, India and Iran.
• hpAsia2, from Northern India, Bangladesh, Thailand and Malaysia.
• hpEastAsia, found in Japan, Korea, Taiwanese Chinese, China and Vietnam.
• hpSahul, carried by natives in Papua New Guinea and the Australian Aboriginals.
• hspMaori, found among Melanesians, Taiwanese Aboriginals and Polynesians.
• hspAmerind, carried by Native Americans.

This is interesting and points out closed groups moving with their own bacterial strains into the territories they peopled. But it also shows links between them that are not so clearly revealed by the human genome studies (mtDNA or Y chromosme sequencing). Below is Figure 2., from [1], the interesting part is not the map, but the trees:

H. pylori Asian strain, in Asia and tree. From [1]

The captions from the original text are: "(A) Map of sampling locations of hspEAsia haplotypes in Southeast Asia... (B) Neighbor-joining tree from pair-wise FST values of hpEastAsia haplotypes rooted with haplotypes of the population hpSahul. (C) Neighbor-joining tree of pair-wise FST values of the subpopulation hspEAsia. doi:10.1371/journal.pone.0022058.g002" [1].

Look at B and C, the hspAmerind is completely separate from all the Asian and Melanesian - Polynesian branches. Very distinct indeed. They split off long ago, close to the split with hspSahul.

Looking at it from the perspective of my last post NRY haplogroup C, Eurasia and Homo erectus It is clear that hspMarori does not reflect the ancient C2 Y chromosome hapoltype of NG, instead it reflects the later arrivals from Taiwan. hspSahul on the other hand does reflect the archaic people that occupied Sahul with the C4 and C2 haplotypes. HspEAsia reflects C1 (Japan), C3 and C*. So clearly hspAmerind is the ancient C haplotypes found in America.

What about the Indian C5? and C-M130 marker, or the archaic European C6?

Let's look at the other figure from [1]:

hspEurope in Asia, map and Tree. From [1]

European varieties split into two main branches North Europe (top) and France - Spain (bottom). The La Braña remains (7 ky old) with C6 haplotype were found in Spain.

The hspEurope is also found in Asia: in India and S.E Asia. This is what the paper (Breurec S., et al., 2011) [1] deals with in detail, trying to find out how did a specifically European variety of H. pylori reach the heart of South East Asia. The conclusions are remarkable:

Since it is found at high frequencies among Khmer (52%) and the variety was similar to the one found among Thais, but different to the French type, it is clear that it was not introduced into those populations due to Colonial contact with the French in Indochina (Vietnam, Laos, Cambodia), it is far older, and the paper suggests that "hpEurope bacteria in Southeast Asia might be a marker for an old human migration that predated the European colonial history." [1]

The link, as can be seen in the neighbor-joining tree (based on these pairwise FST values), shown above clusters the S.E. Asian and Indian varieties in a distinct group linked to the European types.

Recent introduction by Indians into S.E. Asia is also discarded because Malays, Thai and Khmer are closer to each other than to the Indians (from India or those that migrated to Malaysia).

Once again the paper concludes that this "suggest[s] a common origin of these strains and argu[e] against an exclusively recent acquisition of Malaysian hpEurope strains from Indian immigrants..." [1]. I fully agree, these are ancient strains that somehow were introduced into the region and prevailed despite the introduction of the hspEAsia.

The question is when did they reach Southeast Asia. The paper supports a two stage arrival: one to India and another onwards, into S.E. Asia: "an old introduction of hpEurope strains into the Indian subcontinent by Indo-Aryan migration (4000–10000 BP) as previously described. This was followed by subsequent eastward migrations of their descendants into Southeast Asia, carrying hpEurope strains in their stomach, probably within the last 3000 years." [1].

I disagree with both dates; they are too recent. Furthermore, allow me to quote another paper on H. pylori in the region (Tay et al., 2009): "there is no evidence that ancestral Malays migrated from India [or evidnece that] supports Malays sharing direct common ancestry with Indians." [2].

The paper adds: "Therefore for the Malay population, the ancestry of H. pylori does not reflect human ancestry as in other populations." [2]. I fully agree, it does not reflect the human ancestry of these people but their archaic ancestral Homo erectus ancestry.

Tay et al., are at a loss to explain the Indian - Malaysian link, and bogged down by the constraints of orthodoxy overlook the most parsimonious explanation. I will quote the paper (bold is mine):

"Another potential source of H. pylori for non-aboriginal Malays is the Orang Asli population, who originated from early human migration out of Africa.
The Orang Asli is likely to have taken the "Southern Route" into South East Asia to reach Malaysia by traveling along the Indian Ocean Coast line 50–65,000 years ago.
Therefore the Orang Asli H. pylori, if it exists, may share common ancestry with the Indian H. pylori, leading to the observed similarity of Malay isolates to Indian isolates."
So far so good, that is exactly the correct explanation, but then they dismiss it!.
"However given that other earlier H. pylori populations such as the Maori and American Indian populations can be readily identified, one would expect that the Orang Asli H. pylori population would be unique and identifiable after such a long period of separation, arguing against acquisition from Orang Asli population and in favour of acquisition from the Indian population." [2]

Actually the Orang Asli H. pylori and that of all S. E. Asians as well as the Indians, is the original archaic hspEurope in its "Asian Clade" as shown in the figure above.

Proof of the ancient origin of the Indian clade of hspEurope is found in S Manjulata Devi et al., (2007) [3], who were cited by [2] above, and who wrote: (bold mine)

"we suggest that H. pylori might have arrived in India probably at the same time when Indo-European language speaking people crossed into India (~4000–10,000 years before present). Alternatively, the unquestionable common origin of Indian strains with the European ones could be actually more ancient, following the upper Paleolithic spread of Homo sapiens in Eurasia, as suggested by mtDNA variability, and our data on H. pylori MLST do not rule out this possibility." [3]

This is where Breurec S et al., picked their date of 10 - 40 ky, but it is clear that S Manjulata Devi admits that an earlier date is possible, the actual OoA event into Asia.

The uniform dispersal within distinct geographic locations is in my opinion a clear indicator of an extremely ancient relationship between H. pylori and hominins, one that reflects, in my opinion, the most ancient dispersal of humans from Africa, the OoA event of H. erectus and their migrations.

The African diversity reflects perhaps even more ancient roots. But in Eurasia and the Americas the H. pylori lineages mirror the Y chromosome C haplogroup regions. As I conjectured in my previous post:

Current C hg. distribution reflects the migration of Homo erectus out of Africa 1.8 Mya. A band of a few hundreds of people walking into Asia with the CF haplogroup, splitting in the Persian Gulf by acquiring the M130 marker, and thus forming C haplogroup. They moved across South Asia keeping their C hg. identity during their long trek (note that since mutation rates are slower than accepted, no mutations arose during this period).

Finally reaching the Homeland from which it differentiated into its current haplogroups, in the North of S. E. Asia. From there they spread out. Some moved into NG, Australia mutating (slowly) into C2 and C4. Others went back into India and mutated to C5. The core in S.E. Asia evolved into C* while others went north forming C1 and C3.

A group did not take the Eastern route and went West into Europe forming C6 there. Maybe it will be sequenced someday from the bones at Sima de los Huesos...

Erectus entered America long ago, and the patchy C3* distribution in South America is what remains of a once widespread coverage of H. erectus in the New World...

So we see the correlation: hpEurope = C6, hpAsia2 = C5 - C* hpEastAsia = C3 - C1, hpSahul = C2, C4, hspMaori = C2 (Polynesia), hspAmerind = C3 (America).

Sources

[1] Breurec S, Guillard B, Hem S, Brisse S, Dieye FB, et al., (2011). Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia. PLoS ONE 6(7): e22058. doi:10.1371/journal.pone.0022058
[2] Tay CY, Mitchell H, Dong Q, Goh KL, Dawes IW, et al., (2009).Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population. BMC Microbiol 9: 126. doi:10.1186/1471-2180-9-126
[3] S Manjulata Devi, et al., (2007). Ancestral European roots of Helicobacter pylori in India. BMC Genomics 2007, 8:184 doi:10.1186/1471-2164-8-184

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

Ulcer causing bacteria and Neanderthals in America

About half the human population carries a Gram-negative bacteria called Helicobacter pylori (hp for short) in their stomachs. It is a microaerophilic bacterium belonging to the Epsilonproteobacteria which was discovered in 1984, and has lived inside of our ancestors for many tens of thousands of years.

It can cause several illnesses: peptic and duodenal ulcers, chronic gastritis and even cancer. Fortunately these diseases only occur in a minority of those infected with the bacteria. Most of us don't even notice we carry it, and will not notice any problems.

The interesting part is that it is transmitted mainly within families and, is a clear indicator of lineage and origin of those families. There are however instances of horizontal transmission (attributed to sharing drinking water in rural South America), but inter ethnic exchange is rare and may take centuries (as indicated by the hp Europe strain found among black South Africans). [1]

The bacteria is commonly transmitted person-to-person by saliva, and in developing countries, by fecal contamination of food or water.

Genetics and Helicobacter pylori

The original stock of hp evolved with their human hosts and diverged into several major hp populations, spreading across the globe with our migrating ancestors (hpAfrica1, hpEurope, hspEAsia, and hspAmerind,named after their geographical locations).

As can be expected, and following the logic that America was the last corner of the world to be inhabited, the literature stresses the "similarities between the hspAmerind and hspEAsia populations suggest[ing] that the first colonizers of the New World brought H. pylori with them..." from Eastern Asia, horizontal transmission is highlighted by an "apparent dominance by the hpEurope population at least in Latin America" [2].

The former may not be so true, but the latter definitvely is: the European hp strains were evidently transmitted due to admixture between natives and the large migration of Europeans to Latin America.

Regarding the "similarity" between East Asian and Amerindian hp, check this:

Some strains differ in their proteins which affect their hosts in differwnt ways. The most studiwd ones are CagA and VacA:/p

"However, the single-gene trees for cagA and vacA show strong divergence [between Amerindian hp] from both hspEAsia and hpEurope counterparts. The exaggerated evolution of these genes that has occurred over the ~15,000 years since the arrival of Amerindian ancestors to the Americas makes them less suitable for deducing evolutionary relationships but highlights the need to assess the physiological activities of the Amerindian alleles...
... phylogenetic analysis of the host-interactive genes vacA and cagA shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci."[2]

There seems to be some contradiction here. On one hand we are told that Amerindian and East Asian hp are "close" to each other, but then we are told that they is a "Strong divergence" between some of their proteins.

A large difference between strains (i.e. accumulation of mutations) is always taken as an indication of a long period of time separating them. Giving them time to evolve separately (However the paper says that it is an "exaggerated evolution", below we see why.)

In this case, since the authors have adopted the orthodox time frame used in this paper (which is repeated in most papers, of 15 ky for the peopling of America as mentioned above), they cannot assume an ancient split as an explanation. With no other alternative, the authors imagine some host-parasite interaction that favored the "exaggerated evolution" of these unique hp strains!:

"This difference suggests that there has been a greater impact of host interaction on the hspAmerind lineage than on other H. pylori lineages.[...] suggest[ing] that parallel, yet to be identified host polymorphism skewing relevant to both CagA and VacA interactions exists in Amerindians." [2]

A more reasonable explanation

Why not just assume that the H. pylori among Amerindians is really old, ancient, that its differences that set it apart from the H. pylori of Europeans, Africans and East Asians, is due to the long span of time since they hp lineages split.

I could even suggest that the Amerindian strains are unique because they derived from an ancestral strain received from Neanderthals (horizontal transmission - well humans had sex with them, it is likely that some hp got exchanged via mother-child or even through saliva in mate-mate interactions).

The following image shows the CagA phylogenetic tree (Adapted from Fig. 7 in [2]). Notice how Amerindians stand midway between Eurasians on the top and Euro - Africans on the bottom. They are clearly not a branch on the Eurasian side. They are a separate lineage, maybe the ancestral one:

Of course, since orthodoxy upholds the Out Of Africa theory and a 30-15 kya peopling of America, papers are written to conform to (and to confirm) orthodoxy.

See another post (July 4, 2014) on the H. pylori and Homo erectus

Sources

[1] Wirth, T., Meyer, A and Achtman, M., (2005). Deciphering host migrations and origins by means of their microbe. Molecular Ecology 14, 3289–3306 doi: 10.1111/j.1365-294X.2005.02687.x
[2] Mane, S. P., (2010). Host-Interactive Genes in Amerindian Helicobacter pylori Diverge from Their Old World Homologs and Mediate Inflammatory Responses?. doi: 10.1128/JB.00063-10 J. Bacteriol. June 2010 vol. 192 no. 12 3078-3092

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