ancestry_ancestry和ancestor区别

非洲是人类最早进化的地方，今天仍然是一个具有非凡多样性的地方。一个国际科学团队对来自十几个种族、文化、地理和

 

非洲是人类最早进化的地方，今天仍然是一个具有非凡多样性的地方一个国际科学团队对来自十几个种族、文化、地理和语言不同人群的180名土著非洲人进行了新的分析，为人类历史和生物学提供了新的见解，并可能为未来的精准医学方法提供信息。

Africa, where humans first evolved, today remains a place of remarkable diversity. Diving into that variation, a new analysis of 180 indigenous Africans from a dozen ethnically, culturally, geographically, and linguistically varied populations by an international scientific team offers new insights into human history and biology, and may inform precision medicine approaches of the future.

这项工作澄清了人类迁徙历史，包括历史和最近的迁徙历史，并提供了适应当地环境的遗传证据，通过肤色、心脏和肾脏发育、免疫力和骨骼生长等特征表现出来The work clarifies human migration histories, both historical and more recent, and provides genetic evidence of adaptation to local environments, manifested through traits such as skin color, heart and kidney development, immunity, and bone growth.。

这项研究结果发表在《细胞》杂志上，由宾夕法尼亚大学的研究人员领导，对了解非洲人后裔的常见健康状况也有意义而且，由于非洲人口在基因组研究中的代表性不足，这项调查大大扩大了人们对人类遗传多样性的了解这项研究发现了数百万种新的基因组变异，称为单核苷酸多态性（。

SNPs）——DNA序列中一个“字母”的差异——包括许多似乎在健康中发挥作用的变异，为更广泛的人群从基于个体差异的精准医疗中获益奠定了基础The findings, published in the journal Cell and led by University of Pennsylvania researchers, also have implications for understanding health conditions common in people of African ancestry. And, because African populations have been underrepresented in genomic studies, the investigation significantly expands what is known about human genetic diversity. The investigation turns up millions of new genomic variants known as single nucleotide polymorphisms (SNPs) -- differences in one "letter" of the DNA sequence -- including many that appear to play roles in health, laying the groundwork for a broader swath of people to benefit from precision medicine based on individual differences.。

研究人员获得了180个个体的完整基因组序列，其中12个土著群体各15个这项研究是第一次对如此多样的非洲群体进行严格的全基因组测序Researchers obtained complete genome sequences for 180 individuals -- 15 from each of 12 indigenous populations. The study is the first to perform rigorous whole-genome sequencing of such a genetically diverse mix of African groups.。

这12个人口从事或直到最近才从事传统生计：农业、畜牧业或狩猎和采集他们包括非洲四个不同语系的代表：非洲语系、尼罗-撒哈拉语系、尼日尔-刚果语系和霍桑语系The 12 populations practice, or practiced until recently, traditional livelihoods: farming, livestock herding, or hunting and gathering. Together, they include representatives from each of the four different language families present in Africa: Afroasiatic, Nilo-Saharan, Niger-Congo, and Khoesan.。

研究团队将这些非洲人群的新基因组序列与全球其他人群先前测序的基因组相结合，构建了一个全球家谱Placing the new genome sequences from these African populations in context with other, previously sequenced genomes from populations across the globe, the research team crafted a worldwide family tree.。

Tishkoff说：“推断非洲人口历史非常具有挑战性，因为历史非常复杂”“但是，利用我们的模型，基于基因组变异的共享模式，即使考虑到基因流动——种群迁入和迁出以及杂交，你也可以推断种群何时共享一个共同的祖先。

”"Inferring African demographic history is very challenging because the history is so complex," Tishkoff says. "But, with our models, based on shared patterns of genomic variation, you can infer when populations shared a common ancestor, even when accounting for gene flow -- populations migrating in and out and interbreeding."

当研究小组在他们的模型中允许基因流动时，他们发现，南部非洲科伊桑语的桑族人以及中部非洲雨林居住的狩猎采集者是源头蒂什科夫说：“这是一个非常新颖的结果”先前的分析指出，只有桑族人是从最古老的人群后裔When the team allowed for gene flow in their models, they found that the southern African Khoesan-speaking group, the San, as well as Central African, rainforest-dwelling hunter-gatherers appeared at the root of the tree. "Thats a very novel result," Tishkoff says. Previous analyses had pointed to only the San as descending from the most ancient populations.

他们还发现，20多万年前，圣非和中非狩猎采集群体彼此分离，并与其他已知人群分离They also found that the San and Central Africa hunter-gatherer groups split from one another, and from other known populations, more than 200,000 years ago.。

种群祖先模型发现了一个现已灭绝的“幽灵”种群的证据，该种群可能与当时的其他群体混杂在一起Tishkoff说：“我们没有化石中的古DNA，因为它们在非洲环境中保存得不好，但有一种解释是，它们可能与古老的种群混合在一起。

”Population ancestry models turned up evidence of a now-extinct "ghost" population that may have intermixed with other groups at the time. "We dont have ancient DNA from fossils because they dont preserve well in an African environment, but one explanation is there could have been mixing with an archaic population," Tishkoff says.

这一发现为语言学支持的人口结构理论提供了支持语言学家们一直在争论说霍桑语的群体是否真的有着密切的联系，这些群体的语言共享点击辅音，但在其他特征上却非常不同根据基因组结果，尽管这些群体在数万年前就已经分化，但有证据表明，在过去的。

10000年中，所有这些群体可能在东非有着共同的起源，并共享了最近的基因流The findings add support to linguistics-backed theories of population structure. Linguists have debated whether Khoesan-speaking groups -- whose languages share click consonants but are highly distinct in their other features -- were truly closely related. According to genomic results, though these groups diverged tens of thousands of years ago, there is evidence that all of them may have shared a common origin in East Africa, and shared more recent gene flow, during the last 10,000 years.。

Tishkoff说：“我们提出的建议是，这些说点击语的群体，甚至雨林狩猎采集者，可能都有东非血统，尽管他们已经失去了原始语言，并采用了邻近班图语人口的语言”“这两个群体可能朝着不同的方向分裂，哈扎人和桑达韦人（来自坦桑尼亚。

的霍桑语使用者）留在当地，桑人（来自博茨瓦纳的霍桑人）向南迁移”然而，对现代和古代DNA的分析表明，哈扎和桑达威人的祖先与桑人的祖先之间存在基因流动，这可能会解释他们语言中的一些相似之处"What we propose is that there may have been an East African origin for these click-speaking groups, and maybe even the rainforest hunter-gatherers as well, though theyve since lost their original language and adopted the language of the neighboring Bantu-speaking populations," says Tishkoff. "The groups may have split in different directions, with the Hadza and the Sandawe (Khoesan speakers from Tanzania) staying local and the San (Khoesan speakers from Botswana) moving south." However, analysis of modern and ancient DNA indicates that there has been gene flow between the ancestors of the Hadza and Sandawe and the ancestors of the San, which could potentially explain some similarities in their language.。

新测序的基因组确定了3200万个SNP，其中包括500多万个从未被编目的SNPThe newly sequenced genomes identified 32 million SNPs, including more than 5 million that had never before been cataloged.。

坦桑尼亚坎帕拉国际大学的研究合著者托马斯·B·Nyambo说：“3200万个SNP的分析，让人们重新认识到在以前被边缘化的地区开展遗传研究的重要性”“这是阐明进化趋势及其在定制诊断和治疗中的含义的前进方向。

”"The 32 million SNPs that were analyzed have just shed a new light on the importance of extending genetic studies in regions that have been previously marginalized around the globe," says study co-author Thomas B. Nyambo of Kampala International University in Tanzania. "This is the way forward in the elucidation of evolutionary trends and their implication in tailored diagnostics and therapeutics."

当研究团队将先前识别的SNP与临床研究中广泛使用的数据库中的SNP进行交叉引用时，他们发现研究中在非洲个体中发现的许多变体有致病性When the research team cross-referenced the previously identified SNPs with those in a widely used database used for clinical studies, they discovered many of the variants found in the African individuals in the study had been classified as pathogenic.。

“这并不意味着非洲人口有更多的‘致病性’变异，”范少华（Shaohua Fan）说，他是这项研究的主要作者，在宾夕法尼亚大学完成了博士后研究，现供职于中国复旦大学“相反，它强调了在人类遗传研究中纳入种族多样性人群的强烈需求，特别是因为在临床研究中，稀有性是决定一种变体致病性的一个标准。

”"This does not mean African populations have more pathogenic variants," says Shaohua Fan, a lead study author who completed a postdoc at Penn and is now at Chinas Fudan University. "Rather, it emphasizes a strong need to include ethnically diverse populations in human genetic studies, especially because rarity is one criteria for determining a variants pathogenicity in clinical studies."

换言之，这些变体中的一些可能被错误地归类为与疾病相关，只是因为它们在其他人群中非常罕见，例如在这些临床数据库中占主导地位的欧洲人In other words, some of these variants may have been miscategorized as associated with disease only because they were so uncommon in other populations, such as Europeans, which dominate these clinical databases.。

博茨瓦纳大学的Sununguko Wata Mpoloka表示：“全面评估遗传变异已被用作研究人类疾病的策略，并为识别与疾病易感性和进展相关的新基因座提供了巨大的力量”“在此类研究中纳入博茨瓦纳等研究不足的土著人口，将极大地促进对精准医学的理解，并可能因此针对此类人群研究药物。

”"Comprehensively assessing genetic variants has been used as a strategy to study human disease and provides tremendous power to identify new loci associated with disease susceptibility and progression," says Sununguko Wata Mpoloka of the University of Botswana. "Including understudied indigenous populations like those from Botswana in such studies will contribute tremendously to an understanding of precision medicine and could lead to tailormade drugs specific to such populations."

这些变体中的一些确实可能在健康和疾病中发挥有意义的作用为了了解这些关联，研究人员不仅将突变与现有数据库和已发表的研究进行了比较，还观察了这些变化是发生在蛋白质的编码区，还是发生在可以调节基因表达的生物相关途径和过程的区域。

他们还寻找在不同人群中以显著不同频率发生的一种突变，即等位基因这些差异可能是因为等位基因在当地适应不同环境中发挥作用，并被积极选择，可能是因为它们给携带它们的人带来了一些优势Some of these variants may indeed play a meaningful role in health and disease. To get at these associations, the researchers not only compared mutations to existing databases and published studies, but also looked to see whether the variations occurred in the coding regions for proteins or in regions that could regulate gene expression for biologically relevant pathways and processes. They also looked for versions of a mutation, known as alleles, that occur at significantly different frequencies in different populations. These differences may arise because the alleles play a role in local adaptation to diverse environments and are positively selected, presumably because they confer some advantage to the people who carry them.

这些分析中出现了几个显著的变体例如，在南部非洲的San人群中，该团队发现PDPK1基因附近有大量SNP，其他科学家已经证明，PDPK1在小鼠色素沉着中起作用Tishkoff实验室的博士后研究员、研究合著者冯元庆表示：“根据我们实验室之前的研究，我们知道，与其他非洲人群相比，桑族人的肤色相对较浅。

”“因此，我们假设PDPK1附近的SNP可能影响人类的色素沉着”Several notable variants emerged from these analyses. In the San population of southern Africa, for example, the team found high numbers of SNPs near the PDPK1 gene, which had been shown by other scientists to play a role in pigmentation in mice. "Based on prior studies in our lab, we know that the San have relatively light skin color compared with other African populations," says Yuanqing Feng, a postdoctoral researcher in the Tishkoff lab and a study co-author. "Thus, we hypothesized that SNPs near PDPK1 may affect pigmentation in humans."。

为了为这一假设提供机制证据，研究人员测试了在培养皿中生长的皮肤细胞中，这些SNP中的一个在San人中很常见他们发现，抑制含有该变体的区域改变了PDPK1的表达水平，并降低了实验室培养的皮肤细胞中皮肤色素黑色素的水平。

To generate mechanistic evidence for that hypothesis, the researchers tested the effect of one of these SNPs -- shown to be common in the San -- in skin cells grown in a petri dish. They found that inhibiting the region containing the variant altered expression levels of PDPK1 and reduced the levels of the skin pigment melanin in the lab-grown skin cells.

研究还发现了与健康和功能的其他联系该团队的分析发现，在中非狩猎采集者中，与骨骼生长相关的基因附近存在大量变异这些群体以身材矮小而闻名，据信这对他们居住的茂密雨林环境有利在东非的牧民群体中，该团队发现了在肾脏发育和功能中发挥作用的基因附近的变体的富集，这可能是对干旱条件下生活的适应。

在东非的哈扎狩猎采集者中，他们发现在心脏发育中起作用的基因附近有一种独特的变体富集Other connections with health and function emerged from the study. The teams analysis found a large number of variants near genes associated with bone growth in the Central African hunter-gatherers. These groups are known for their short stature, which is believed to be advantageous for the thick rainforest environment where they live. In pastoralist populations from East Africa, the team discovered enrichment for variants near genes that play a role in kidney development and function, possibly an adaptation to living in arid conditions. And in the Hadza hunter-gatherers in East Africa, they found a unique enrichment of variants near genes that play a role in heart development.

Tishkoff说：“我的实验室现在正在追踪这些基因中的一些，看看我们能否了解心肌发育的遗传学”“如果我们了解这些基因是如何调节的，这可能会给我们一个线索，说明为什么有些人有心血管疾病的倾向要了解异常功能，首先必须了解正常功能，我们推测，这些人的生活方式有一定的道理，比如必须走很远的路，这可能有利于心脏发育和功能的某些变化。

"My lab is now following up with some of these genes to see whether we can learn about the genetics of heart muscle development," says Tishkoff. "If we understand how these genes are regulated, that could give us a clue as to why some people have a tendency toward cardiovascular disease. To understand abnormal function, you first have to understand normal function, and we speculate that theres something about these individuals lifestyles -- having to walk incredibly long distances, for example -- that might make it advantageous to have certain changes in how the heart develops and functions."

"此外，研究人员还发现了尼罗-刚果血统人群中与血压控制相关的基因变体，这些西非群体与大多数非洲裔美国人的血统相同Tishkoff说：“在美国，非洲裔美国人的高血压和糖尿病发病率很高，这主要是由于社会经济因素。

”“但可能有一些遗传风险因素，加上他们生活的环境，会影响他们患病的风险其中一些因素在非洲环境中可能是适应性的，但在美国环境中则是不适应性的”In addition, the researchers found gene variants related to blood pressure control in people with Nilo-Congo ancestry, West African groups that share ancestry with people from whom most African Americans are descended. "Theres a high incidence of hypertension and diabetes in people of African ancestry in the United States, and thats largely due to socioeconomic factors," Tishkoff says. "But there could be some genetic risk factors that, together with the environment in which they live, influence their risk for disease. Some of these could be adaptive in an African environment but maladaptive in a U.S. environment."

有一天，这些新的数据点可能有助于为精确医学方法提供信息，这些方法依赖于了解遗传学和其他个体差异如何影响人们的疾病风险、对药物的反应等These new datapoints may one day help inform precision medicine approaches that rely on understanding how genetics and other individual differences affect peoples disease risk, response to drugs, and more.。

Journal Reference:Shaohua Fan, Jeffrey P. Spence, Yuanqing Feng, Matthew E.B. Hansen, Jonathan Terhorst, Marcia H. Beltrame, Alessia Ranciaro, Jibril Hirbo, William Beggs, Neil Thomas, Thomas Nyambo, Sununguko Wata Mpoloka, Gaonyadiwe George Mokone, Alfred Njamnshi, Charles Folkunang, Dawit Wolde Meskel, Gurja Belay, Yun S. Song, Sarah A. Tishkoff. Whole-genome sequencing reveals a complex African population demographic history a