The genetic legacy of early Neolithic farmers

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

There is a broad consensus that agriculture first appeared in the Fertile Crescent and that agricultural techniques rapidly spread throughout Europe. It is however unclear whether the presence of agricultural artefacts indicates a wave of expansion of Neolithic farmers displacing previously established populations or simply the spread of farming practices. The classical population genetics view first championed by Cavalli-Sforza and colleagues points to a wave of advance of farming populations displacing the local populations, and thus suggesting a mainly Neolithic origin of the gene pool of Western Europe (80 per cent). However some recent work based on different data and statistical methodologies reached strikingly different conclusions, with the Neolithic component of the European gene pool being estimated to be around 15 per cent to 20 per cent. Both camps are currently entrenched and while this debate may to some extent be solved by the development of more sophisticated statistical methods, failure to resolve this key debate appears in the main due to the small and highly biased sample available to represent the descendents of early Neolithic farmers. This prompted us to collect a large sample (2,500) from 23 ethnic groups in Iran. These will be analysed for both Y chromosome (SNPs and STRs) and mtDNA polymorphisms (HVI and a few diagnostic SNPs). We will analyse the genetic diversity and its apportionement at this regional scale, trying in particular to identify populations that might be most related to the early Neolithic farmers, thus providing a better idea of their genetic makeup. We will then pool this new sample with existing data to obtain improved estimates of the proportion of Neolithic ancestry in the European gene pool. These new data should also help clarifying the spread of Indo-European languages and allow tackling the spread of agriculture east and southwards.
 
Description When we started working on this project, the working hypothesis was that worldwide human populations formed well defined clusters roughly corresponding to continents. However, there was also evidence for a genetic cline between the Near East and Europe that has been interpreted as a signal of the expansion of Neolithic farmers from the Fertile Crescent. Concomitantly to the proposed lab work (objectives 1 and 2), we started analysing the available autosomal genetic data within a new geographically explicit framework. To our surprise, we found smooth patterns in the geographic distribution of human genetic diversity in whichever region of the world we were looking at. Genetic differentiation between populations increases essentially linearly with geographic distance computed along landmasses. Even more striking was the observation that geographic distance along landmasses from Sub-Saharan Africa is an excellent predictor of the genetic diversity of human populations throughout the world, with diversity decreasing monotonously with increasing geographic distance from the putative cradle of anatomically modern humans. These results provide compelling evidence for a single recent African origin of all modern humans and challenge the notion of discrete human clusters or races7.

Several papers focusing on Eurasia mistakenly attributed these clines exclusively to the Neolithic expansion rather than to the prior colonisation of the world by our ancestors. In light of the worldwide clinal patterns in human genetic diversity, modelling the expansion of Neolithic farmers and their contribution to the European genetic make-up turned out to be far more complex than initially envisaged (objectives 4 and 5). It is only now that we start having the necessary analytical tools to model "clines within clines" and we expect to be able satisfactorily to address these issues over the next year or two. A somewhat less ambitious objective (point 3) was the description of the genetic structure of the current populations inhabiting Iran and neighbouring countries. This aspect of the work did lead to fewer publications than we might have hoped mostly because some of the results were deemed too sensitive to be published and could have put at risk dome of the donors of the DNA. These included the genetic makeup of Iranian Zoroastrians and other minorities as well as a study on Sayids.

Despite the delays and minor setbacks encountered, the project has been a success overall. In addition of the planned work we also expanded the analytical tools developed within this project to a series of important related biological questions. We could show that the distribution of MHC I class sequence variation had been shaped both by human colonisation history and the relative pathogen richness in various regions of the world. We also analysed skull morphometric traits and were able to reproduce patterns very similar to the ones observed for neutral genetic diversity. A joint analysis of spatial genetic patterns in the gut bacterium Helicobacter pylori and its human host allowed us to demonstrate an intimate association predating the exit out of Africa. Finally, we could show that mitochondrial DNA sequence variation has likely been partly shaped by climate and were able to identify two plausible candidate SNPs, which had been previously independently identified as involved in mitochondrial calcium dynamic and mitochondrial matrix pH.
Exploitation Route The work has been influential in the development of spatially explicit models for the analysis of genetic/genomic data and has led to follow-up studies by several groups both on humans and other organisms.
Sectors Digital/Communication/Information Technologies (including Software),Environment,Culture, Heritage, Museums and Collections
 
Description We developed a sophisticated spatially explicit model for the colonization of the world by our ancestors using past climatic reconstructions and extensive genomic data from extant and ancient human populations. We showed that past climatic variation was a major driver for past human expansions and migration and refined the dates of arrival of humans in different parts of the world. The framework can be used as a null model when testing hypotheses about natural selection having affected specific parts of the human genome. Several publications from this grant have been highlighted in comments or News and Views in the scientific literature. The media impact has also been appreciable, with radio and television coverage and over 300 newspapers in about 30 countries running stories on the results. Finally, the 2007 nature paper on human phenotypic variation has been selected as a research highlight for the BBSRC 2007-2008 Report to Parliament.
First Year Of Impact 2009
Sector Culture, Heritage, Museums and Collections
Impact Types Cultural,Societal