图片说明：Novembre小组在研究中得到的遗传地图，根据1387个样本的基因组信息确定出他们在图中的坐标位置。不同字母缩写代表研究对象自称的出生国家。从中可以看出，遗传地图与地理地图的相似度。（图片来源：Nature）

    欧洲的历史上充满着战争、入侵和移民，这些因素似乎可以彻底地将不同人种混合在一起。然而，美国和荷兰科学家独立进行的两项最新研究表明，一个欧洲人的基因组信息足以表明他的地理起源，欧洲人的基因地图和地理地图间存在着一种映射关系。相关论文分别发表在《自然》和《当代生物学》杂志上。

    领导其中一项研究的是美国加州大学洛杉矶分校的人类群体遗传学家John Novembre，他说，“这一结果说明地理位置确实有影响。”不论语言、移民和通婚，欧洲人的遗传差异几乎完全与出生地相关。不过，这并不意味着欧洲各个民族和国家间的遗传差异性很大。领导另一项研究的荷兰鹿特丹大学的Manfred Kayser表示，“欧洲的遗传多样性真的不多。”

    尽管是两项独立研究工作，但它们所用的方法基本相同，都是通过分析数千位欧洲人基因组中的微小差异——单核苷酸多态性（SNPs）。同时，这两项研究中的一些DNA样本也是相同的，它们由GlaxoSmithKline制药公司搜集，用于调查与药物副作用相关的基因。

    对每份个体基因组而言，研究人员都破译了数十万个SNP。利用新一代基因芯片，可以一次测定基因组中的50万个碱基组成。然而，为了对两套基因组的差异进行全面的评估，他们利用一种数学手段，将数十万计的SNP转化成两个坐标，每个人的基因组就用一个点来代表。两个点间的距离越大，表明他们基因组的差异也越大。

    当两支研究小组在单一图表上标出代表数千个个体基因组的点后，一张明显的欧洲地图出现了。西班牙和葡萄牙人的基因组“点”聚集在法国人的西南面，而代表意大利人基因组的“点”则在瑞士人的东南部尤为突出。

    这张地图的精确性令人惊讶。当Novembre小组将一张地理政治学地图放在遗传地图上后，半数的基因组“点”落在研究对象自称的出生地192公里的范围内，而落在434公里范围内的达到了90%（父母来自不同国家的个体不包括在此分析内）。

    两组研究人员同时发现，南部欧洲的遗传多样性比北欧、英国和爱尔兰更为丰富。Kayser认为，这与3.5万年前、2万年前和1万年前几次较大规模的迁入欧洲事件十分吻合。每次都是南方的人群向北入侵。美国密歇根大学的遗传学家Noah Rosenberg表示，“基因反映地理学的模式本质上可以从人们缓慢移动和主要与近邻联姻上预期出来。”

    由于目前的基因芯片只探测常见基因变异可能发生的位点，因此，Novembre认为，随着基因鉴定技术的不断发展，将有像单个村庄中才有的基因变异被整合入芯片中，而科学家也有可能得到精确得多的欧洲人地理起源。

Nature，doi:10.1038/nature07331，John Novembre, Carlos D. Bustamante

Genes mirror geography within Europe

John Novembre1,2, Toby Johnson4,5,6, Katarzyna Bryc7, Zoltán Kutalik4,6, Adam R. Boyko7, Adam Auton7, Amit Indap7, Karen S. King8, Sven Bergmann4,6, Matthew R. Nelson8, Matthew Stephens2,3 & Carlos D. Bustamante7

Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations1, 2, 3, 4, 5. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing6; an individual's DNA can be used to infer their geographic origin with surprising accuracy—often to within a few hundred kilometres.

Current Biology，Vol 18, 1241-1248, 26 August 2008，Oscar Lao, Manfred Kayser

Correlation between Genetic and Geographic Structure in Europe

Oscar Lao,1,22 Timothy T. Lu,2,22 Michael Nothnagel,2 Olaf Junge,2 Sandra Freitag-Wolf,2 Amke Caliebe,2 Miroslava Balascakova,3 Jaume Bertranpetit,4 Laurence A. Bindoff,5 David Comas,4 Gunilla Holmlund,6 Anastasia Kouvatsi,7 Milan Macek,3 Isabelle Mollet,8 Walther Parson,9 Jukka Palo,10 Rafal Ploski,11 Antti Sajantila,10 Adriano Tagliabracci,12 Ulrik Gether,13 Thomas Werge,14 Fernando Rivadeneira,15,16 Albert Hofman,16 André G. Uitterlinden,15,16 Christian Gieger,17,18 Heinz-Erich Wichmann,17,18 Andreas Rüther,19 Stefan Schreiber,19 Christian Becker,20 Peter Nürnberg,20 Matthew R. Nelson,21 Michael Krawczak,2,23 and Manfred Kayser1,23

Understanding the genetic structure of the European population is important, not only from a historical perspective, but also for the appropriate design and interpretation of genetic epidemiological studies. Previous population genetic analyses with autosomal markers in Europe either had a wide geographic but narrow genomic coverage [1, 2], or vice versa [3, 4, 5, 6]. We therefore investigated Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations, widely spread over Europe. Although we found only a low level of genetic differentiation between subpopulations, the existing differences were characterized by a strong continent-wide correlation between geographic and genetic distance. Furthermore, mean heterozygosity was larger, and mean linkage disequilibrium smaller, in southern as compared to northern Europe. Both parameters clearly showed a clinal distribution that provided evidence for a spatial continuity of genetic diversity in Europe. Our comprehensive genetic data are thus compatible with expectations based upon European population history, including the hypotheses of a south-north expansion and/or a larger effective population size in southern than in northern Europe. By including the widely used CEPH from Utah (CEU) samples into our analysis, we could show that these individuals represent northern and western Europeans reasonably well, thereby confirming their assumed regional ancestry.