Bacteria tell the tale of human intercourse

By Razib Khan | July 20, 2011 1:39 am

The Pith: the genetic relationships between bacteria in our stomach can tell us a lot about the relationships between various groups of people. Additionally, the distribution of different strains of bacteria may have significant public health implications.

The above image is from a paper which was pushed online yesterday in PLoS ONE: Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia. It’s a paper which caught my attention for several reasons. First, I’ve exhibited some curiosity about the history and prehistory of Southeast Asia of late. Elucidating this region’s historical dynamics may bear upon more general questions of human evolutionary and cultural process. Second, H. pylori is a fascinating organism whose connection to specific human populations is tight enough that it can shed light on past interactions of different groups. In short, just like humans H. pylori exhibits regional specificity and local history. But additionally, H. pylori is also subject to natural selection after introduction into a new population, and so can serve as a window upon cultural contacts which might otherwise leave a light demographic footprint. In other words, the spread of H. pylori across human populations may be compared to the spread of Buddhism. This religion came to China and Japan with some Buddhists of South and Central Asian origin, but by and large its spread was memetic rather than through natural increase of a Buddhist population.

First, let’s hit the abstract:

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

H. pylori can be separated into very distinctive lineages of geographically limited scope, despite some horizontal gene flow. One clade seems generally restricted to western Eurasia, another to eastern Eurasia, and there are some Africa specific lineages as well. But within these particular clades one can drill-down to a finer-grain. For example, there are Indian lineages within the broader west Eurasian family of strains. As mutation over time results in the build up of distinctive variants in localized populations, a simple assessment of mutational steps between lineages can allow one to infer a tree of descent from a common ancestor.

Let’s tack for a moment to some history without microbial goodness. To some extent Southeast Asia can be considered part of “Greater India,” more or less. This is most evident in Thailand and Cambodia, two nations which are cultural heirs to the Khmer civilization which produced Angor Wat. The religious and artistic sensibilities of both these modern societies are deeply imprinted by South Asian norms through that precursor polity. The Theravada Buddhism of these societies still has a vital connection to South Asia (especially Sri Lanka) and is more obviously Indian in its sensibility than for example the Zen sect of Japan (which derives from Chinese Chan). In Vietnam there remains a small group of Malay Cham Saivite Hindus, the remnants of the Champa Empire.

The affinities in maritime Southeast Asia are a bit clouded because of the interposition of Islam between moderns and the Dharmic past. Only the Balinese remain as a vital living heir to the Indian-influenced polities of early Indonesia, Srivijaya and Majapahit. Despite this notional reality the Indian influence remains discernible even among Muslim Indonesians, in particular in East Java, where shadow puppet shows of the Ramayana remain popular. Like Angor Wat, Borobudur in Java is a testament to the monumental Indian past. But even the avowed Islamic flavor of modern maritime Southeast Asia may have some Indian connection, insofar as there is the possibility that South Asian Muslims were critical players in the eastern Indian ocean trade network which slowly Islamicized over the course of the second millennium.

We are then presented with the question: if the Indian influence in Southeast Asia was so strong in the past, where are the genes of Indians? The authors note that mitochondrial DNA analyses, the maternal lineage, show no South Asian specific lineages in appreciable frequencies among native populations. A fixation on mtDNA seemed rather strange to me for two reasons. First, with the PanAsian SNP data set there’s some autosomal data. Second, there are strong reasons to suppose that Indian migrants would be male. The myths and sketchy historical references of this period don’t seem to envisage mass folk migrations, where Indian men bring their women and children and recreate their homelands. Rather, often these men are portrayed as religious specialists or military leaders of genius. The authors note that there is evidence of Indian artisans in Thailand ~2,000 years ago. This is eminently plausible, there are references to towns of Indian merchants in Sumeria ~4,000 years ago! But again, there is no reason that these artisans necessarily brought their wives. Rather, if they were purchased for their skills they may simply have been the human property which was the object of capitalist transactions between two autocrats.

The nature of cultural transfer, and the relatively high fidelity of that transfer, implies to me that some Indians did migrate to Southeast Asia. But they were few, and their genetic impact was minimal. Rather, what we see is the power of memes to operate very differently from genes. The Indian memes rapidly swallowed up the cultural commanding heights, and became normative from Java to northern Thailand (northern Vietnam is the exception to this rule, as it was influenced by China).

H. pylori shares many of the same tendencies as memes, despite its more concrete biological character. As bacteria it can spread rapidly within a population, and decouple itself from the endogenous natural increase of its original hosts. That spread can be driven by natural selection which means that it isn’t a good representation of the ancestry of its hosts. But even natural selection can’t erase the inferences one can make about original contacts between distinct groups.

In this paper the authors present evidence from the nature of H. pylori in Southeast Asia that there was tangible physical contact between Indians and Southeast Asians in the antique past. More precisely, below is a figure which shows the nature of relationships of west Eurasian H. pylori lineages in India and Southeast Asia, with European and other west Eurasian samples as a control.

What you see here is that Indian H. pylori is basal to the Southeast Asian branches, though within the same clade against the European lineages. This tells you that there’s an affinity between Indian and Southeast Asian lineages under consideration here, but that that affinity is diminished by a period of separation. This matters because some regions of Southeast Asia, such as Malaysia, have a large Indian population which arrived in the past few centuries. The fact that there is a distinct Southeast Asia specific lineage suggests that there has been a long period of separation between the two populations, and one can’t attribute the frequency of the west Eurasian Indian H. pylori simply to recent contacts. At least in most of Southeast Asia. It turns out that in the Philippines the west Eurasian H. pylori cluster with Spanish populations. This has to be the outcome of hundreds of years of colonialism.

There’s also this fascinating historical and geographical tidbit:

A study on the distribution of H. pylori virulence factor cagA among Vietnamese identified 84% of the strains harbouring the type II of the cag-right motif…which is characteristic for East Asian strains (hpEastAsia), ranging from 76% in Ho Chi Minh city in South Vietnam to 93% in Hanoi in North Vietnam. However, there was a remarkable difference in the frequency of cag-right motif of type I which is predominant in European (hpEurope) strains. While the type I motif was absent from North Vietnam, it was found in 8/49 (16%) of the samples from Ho Chi Minh city near the Mekong delta. Interestingly, prior to annexation by the Vietnamese in the 17th century, this city was an important Khmer sea port known as Prey Nokor…Thus, hpEurope strains also seem to be frequent among Vietnamese in the Mekong delta, and thus the Annamite mountain range that originates in the Tibetan and Yunnan regions of southwest China and forms Vietnam’s border with Laos and Cambodia seem to have shaped an effective natural barrier for the containment of Indian influence in the Mekong basin, explaining the low prevalence of hpEurope strains elsewhere in Vietnam.

The geographic contours of the nation-state of Vietnam as we understand it today are a relatively new phenomenon. The Vietnamese people, the Kinh, are an ancient nation. But for most of the past ~2,000 years what we know as Vietnam was divided between the Kinh in the north, and the Khmers and later Austronesian Chams in the center and south. Unlike the other peoples of Southeast Asia the Kinh looked to the north, to China, as their cultural model. While India’s influence in Southeast Asia (excepting the Chola adventures) has been through “soft power,” the Chinese have periodically ruled Vietnam directly, and otherwise placed it into the category of tributary state.

There needn’t be any geographical determinism here. Projection of cultural or military power declines in proportion to distance. In relation to culture that projection does not decline linearly, but often exhibits a sharp break. The Vietnamese did not move the Annamite range south when they defeated Champa and began to swallow the eastern flank of the Khmer kingdom. Rather, they shifted populations and cultural identities of populations, and therefore the civilizational boundaries. The line which separated Indic and Sinic moved south with the spread of the Kinh and the retreat of the Khmer. This did not eliminate in totality the Indic influence. Hindu Cham remain in Vietnam, while forms of Therevada Buddhism have some purchase in the Mekong delta, unlike in the rest of country where Chinese derived Mahayana reigns supreme. And so it is that Indic H. pylori also remains as a residual in the southern regions of Vietnam, evidence of the trade and cultural networks which bound it to Greater India as some point in the past.

Next let’s look at the distribution of East Asia specific H. pylori:

The figure is hard to read, but here’s the short of it: there are Amerindian, Taiwan-Oceanian, Chinese, and Southeast Asia specific lineages. More specifically the authors attempt to infer the origin of one particular Southeast Asia specific lineage which exhibits some overlap in southern China. This is because they believe that it can trace the migration of the Austro-Asiatics, likely the first agriculturalists in Southeast Asia. The H. pylori strain in question spans southern China to Malaysia. The geographic zone encompasses regions now inhabited by Thai or Malay speakers, but it seems likely that at one point the whole zone was dominated by Austro-Asiatics. The clincher would be to see if Munda from northeast India carry this same H. pylori strain. In fact an analysis of the phylogenetic tree of strains of H. pylori found in Austro-Asiatic populations or their descendants might be able to move the needle on whether they’re exogenous to India or not (the “older” lineages should be basal).

So far I’ve been focused on issues of phylogeny. How populations of humans and bacteria relate to each other. But there are functional and adaptive implications and dynamics at work. In terms of adaptation it seems that some strains of H. pylori are simply more fit than others in some environments. The Spanish presence in the Philippines was very light demographically over the centuries of their colonial rule. There was considerable residential segregation of the Spanish away from the natives, and the Chinese, who outnumbered the Spaniards often by two orders of magnitude. And yet you have a situation where H. pylori of Spanish provenance seems to be dominant. Why? The authors report that there’s a fair amount of evidence that European H. pylori strains are generalists who outcompete the specialist East Asian and Amerindian lineages. I think one can’t ignore the reality that the “European” strains are endemic to a huge swath of western Eurasia, from Europe to India. Because of their large population sizes these lineages probably have more diversity than the other populations, and so can adapt to a wide range of conditions.

A functional and public health concern is that East Asia H. pylori may be the cause of the much higher stomach cancer rates in that region of the world. You probably know that H. pylori is a critical player in ulcers, so its impact in this region shouldn’t be a surprise. Prior to reading this paper I’ve heard that East Asian stomach cancer rates were due to condiments used. This goes to show the difficulty of much of medical science which relies on correlations and rough guesses about causality.

Obviously I’m interested in what markers such as the distribution of pathogens which are reliant on humans can tell us about history. But over the long term the complex interplay between these pathogens, disease risk, and other phenotypic characteristics, is where the real action is going to be.

Citation: 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 : 10.1371/journal.pone.0022058

Image credit: Mark Alexander

CATEGORIZED UNDER: Anthroplogy, Genetics, Medicine
  • Charles Nydorf

    “Let’s tack for a moment to some history without microbial goodness.” Its sentences like this that keep me reading this blog.

  • http://www.eurasian-sensation.blogspot.com Eurasian Sensation

    But for most of the past ~2,000 years what we know as Vietnam was divided between the Kinh in the north, and the Khmers and later Austronesian Chams in the center and south.

    I’d be interested to know how much of the Kinh’s displacement of the Chams was cultural and how much of it was genetic. How much of today’s South Vietnamese are descended from Cham who adopted Vietnamese culture and language? Or indeed, was the earlier Cham settlement of South Vietnam primarily a genetic or cultural takeover?

  • magetoo

    Wow. I usually read these posts pretty lightly, but this was fascinating. (That could be because Guns, Germs and Steel is fresh in memory, of course.) Things I didn’t know that I didn’t know.

  • http://forwhattheywereweare.blogspot.com/ Maju

    I must say that on first read I am skeptic as to how fig. 4, specially as labeled here relates to the other graphs. Let us remember that H. pylori is not any regular beneficial gut bacteria but an infectious one. Only 20% or infected people show symptoms (which can be very nasty) but it is still a rather hostile bacterium.

    Also, according to Wikipedia, “at least half of world population is infected”, what means that maybe as many as 50% of us may not carry it at all. This is a path that I’d like to explore in the case of relatively isolated Philippines, which does not have “Austronesian” variants but a Basque and a Bengali one. If Filipino people had lost (or never had) the bacterium to begin with (maybe a dietary habit or just founder effect), that would avoid the need for high competitiveness that you claim for the European strain because it’s really odd that there is no East Asian strains in Philippines, only Indian (Bengali?) and European (Basque) ones.

    You label one of the putative flows from India as “Dravidian migration”, however this is at least unproven and you have been mislead by the capriciousness of arrow-drawing by the authors. In fig. 3 it becomes apparent that the ‘Asia2′ haplogroup that (arguably) migrated to SE Asia from India is the Bengali one. There is no mention of Tamils at all.

    On the other hand, the ‘European’ haplogroup in SE Asia (but Philippines) corresponds with Andrah Pradesh. These can be assimilated to Tamils very hypothetically but there was never any Tamil migration to Cambodia and Thailand, right? I’d say that this is more like the Hindu influence of some 2000 years ago instead, which may have arrived via Malaysia/Indonesia.

    Back to ‘Asia2′, the more I look at it the less clear I have it migrated from South Asia to East Asia. At least the Bengali and Malaysia-Indian strains seem to be derived within a wholly SE Asian subtree. It is not impossible that at least that strain of the ‘Asia2′ haplogroup coalesced in SE Asia and (back-?) migrated to Bengal from there.

    Whatever the case it is not the story of human intercourse as you say in the title but more the one of human shared meals, most of which were never that intimate, and maybe of shared latrines.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    intercourse doesn’t mean just sex dude:

    http://dictionary.reference.com/browse/intercourse

    the early cultural influences seem to have been south indian specifically (in regards to the techniques of sculpture and the sects of hinduism or buddhism). and the only indian military power which had any impact on southeast asia were the chola of the tamil country.

  • trajan23

    This is way off topic, Razib, but Half Sigma has gone on a weird tangent where he is denying the historicity of Jesus. Half Sigma has basically admitted that he knows practically nothing about either Second Temple Judaism or modern scholarship on Jesus (He seems to be deriving most of his arguments from R.G. Price), and I was wondering if you would be willing to suggest some appropriate books suitable for the layman?

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    How much of today’s South Vietnamese are descended from Cham who adopted Vietnamese culture and language? Or indeed, was the earlier Cham settlement of South Vietnam primarily a genetic or cultural takeover?

    these would be easy questions to answer if we had the data. the 1000 genomes is collecting samples from ho chi minh city right now. if there’s substructure, we should see it there.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    I was wondering if you would be willing to suggest some appropriate books suitable for the layman?

    hm. it’s been so long. what’s your intent? there are so many books. contact me via email, twitter or FB for follow ups

  • Paul Ó Duḃṫaiġ

    The earliest surviving text from the Philippines is the “Laguna Copperplate Inscription” which shows a fair number of Sanskrit loanwords and is dated to about 900AD. So I’m not surprised that a Bengali strain shows up there along with the Spanish ones. It is strange though that no east-asian strains showed up especially as there have been plenty of inward migration from China over the last 300 years as well.

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    #9, natural selection.

  • http://entitledtoanopinion.wordpress.com TGGP

    This is off-topic, but since you’ve followed the story earlier you might be interested in Marc Hauser’s resignation.

    trajan23, I’ve found the Jesus police to be an interesting site.

  • leviticus

    As Razib states at the end, this is a field of research with very real medical benefits. For a specific example, gut flora has been a topic of some interest in the Autism interest community going back at least 2 years.

  • pconroy

    @Leviticus,

    Totally agree!

    I suffer from GERD, which is caused by H. Pylori – as do many in my immediate family. Autistic traits are also common in my family, both my mother and brother probably have undiagnosed Asperger’s Syndrome, while I have probably a mild form of it, and recently my 2.5 yo son was diagnosed with ASD and PDD-NOS.

    Any connection would certainly be of interest, and also any differences in Autistic symptoms in areas with different native H. Pylori strains are prevalent.

    I suspect that just as the last 2 years have been huge for the human genome, the coming years will be huge for the genomes of human microbial flora, gut or otherwise, and their symbiotic relationship and co-evolution with humans!

  • pconroy

    @Trajan23,

    I know your comment is tangential, but I have a copy of Jesephus’s writing, and he lived in the time of the supposed Jesus, but nary a mention of him – so I suspect he didn’t exist. AFAIK the only messianic type figure that did exist in the era was St John the Baptist, who was an Essene.

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Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

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