Genetic Chaos

Friday, May 28, 2004

Traces of Human Migrations in Helicobacter pylori Populations

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.

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East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage

Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that carry them. Conversely, polymorphisms may be used to date the spread of a microbial species when information about their host populations is available. Therefore, we examined polymorphisms in Helicobacter pylori, which persistently colonize the human stomach, to test the hypothesis that they have been ancient inhabitants of humans. Three H. pylori loci that previously have been shown to have phylogeographic affinity have been analyzed for two populations with different ethnic origins from Venezuela. In a group of Amerindian subjects from Amazonia, East Asian H. pylori genotypes were present for each of the loci examined but were absent in a mestizo population from Caracas. These findings provide evidence that H. pylori has been present in humans at least since ancestors of Amerindians migrated from Asia more than 11,000 years ago.

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Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: Lessons from Ladakh

The history of mankind remains one of the most challenging fields of study. However, the emergence of anatomically modern humans has been so recent that only a few genetically informative polymorphisms have accumulated. Here, we show that DNA sequences from Helicobacter pylori, a bacterium that colonizes the stomachs of most humans and is usually transmitted within families, can distinguish between closely related human populations and are superior in this respect to classical human genetic markers. H. pylori from Buddhists and Muslims, the two major ethnic communities in Ladakh (India), differ in their population-genetic structure. Moreover, the prokaryotic diversity is consistent with the Buddhists having arisen from an introgression of Tibetan speakers into an ancient Ladakhi population. H. pylori from Muslims contain a much stronger ancestral Ladakhi component, except for several isolates with an Indo-European signature, probably reflecting genetic flux from the Near East. These signatures in H. pylori sequences are congruent with the recent history of population movements in Ladakh, whereas similar signatures in human microsatellites or mtDNA were only marginally significant. H. pylori sequence analysis has the potential to become an important tool for unraveling short-term genetic changes in human populations.

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The increasingly obvious medical relevance of human genetic variation is fueling the development of a rich interface between medical genetics and the study of human genetic history. A key feature of this interface is a step increase in the size and diversity of genetic data sets, permitting a range of new questions to be addressed concerning our evolutionary history. Similarly, methodologies first developed to study genetic history are being tailored to address medical challenges, including mapping genes that influence diseases and variable drug reactions. In this paper we do not attempt a comprehensive review of human genetic history. Rather we briefly outline some of the complications and challenges in the study of human genetic history, drawing particular attention to new opportunities created by the explosive growth in genetic information and technologies. First we discuss the complexity of human migration and demographic history, taking both a genetic and archaeological perspective. Then we show how these apparently academic issues are becoming increasingly important in medical genetics, focusing on association studies, the common disease/common variant hypothesis, the evaluation of variable drug response, and inferences about gene function from patterns of genetic variation. Finally we describe some of the inferential approaches available for interpreting human genetic variation, focusing both on current limitations and future developments.

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