Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.
Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.
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DOI：
10.1073/pnas.2207544120
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发表时间：
2023-01-03
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
人类已经适应了不同的环境，但很少有研究将基因组的区域与选择的证据与表型联系起来。我们为玻利维亚的Tsimane和Moseten-两个土著美洲印第安人群体-生成了一个基因组、转录组和生物标记物数据的综合数据集。从专注于Tsimane个体的分析中，我们发现了与免疫相关的基因和特征适应的证据，这是有道理的，因为感染对这个种群的生理机能和健康状况有很大影响。使用来自两个群体的表型数据，我们能够将基因类型与潜在优势的免疫和代谢特征联系起来。这项研究扩展了我们对美洲印第安人自然选择的知识，并揭示了以前未描述的进化和生物医学相关的基因座。越来越多的工作利用基因组数据解决了人类对不同环境的适应问题，但很少有研究将假定选定的等位基因与表型联系起来，更不用说在美洲印第安人等代表性较低的群体中了。在代表性不足的人群中对自然选择和基因-表型关系的研究有可能揭示先前未描述的潜在进化和生物医学相关特征的基因座。在这里，我们与居住在玻利维亚低地的两个美洲印第安人齐曼人和莫塞腾人合作。我们最关注的是齐曼人，因为对这一群体的长期人类学研究表明，他们有很高的宏寄生虫和微寄生虫负担，以及轻微的心脏代谢性疾病或痴呆症。因此，我们为Tsimane个体生成了全基因组的基因数据，以研究自然选择，并将其与血液mRNA-Seq以及心脏代谢和免疫生物标记物数据配对，这些数据是从包括两个群体的更大样本中产生的。在Tsimane中，我们确定了21个区域作为选择性扫描的候选区域，以及5个显示多基因选择证据的免疫性状(例如，C-反应蛋白水平和对冠状病毒的反应)。重叠候选区域的基因因已知与免疫相关的特征而高度丰富，如淋巴细胞和嗜酸性粒细胞的丰富。重要的是，我们还能够利用Tsimane和Moseten的广泛表型信息，并将五个区域(包含PSD4、MUC21和MUC22、TOX2、ANXA6和ABCA1)与免疫和代谢功能的生物标记物联系起来。总之，我们的工作强调了将进化分析与人类学和生物医学数据配对以深入了解与健康相关的特征的遗传基础的效用。
Humans have adapted to diverse environments, but few studies have linked regions of the genome with evidence of selection to phenotypes. We generated an integrative dataset of genomic, transcriptomic, and biomarker data for the Tsimane and the Moseten—two indigenous Amerindian populations in Bolivia. From analyses focused on Tsimane individuals, we found evidence for adaptation at genes and traits involved in immunity, which makes sense given that infection has strong effects on physiology and fitness in this population. Using phenotypic data from both populations, we were able to link genotypes to the immune and metabolic traits that are potentially advantageous. This study expands our knowledge of natural selection in Amerindians and uncovers previously undescribed loci of evolutionary and biomedical relevance. A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype–phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.
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影响因子：
3.7
作者：
Cairns R;Fischer AW;Blanco-Munoz P;Alvarez-Guaita A;Meneses-Salas E;Egert A;Buechler C;Hoy AJ;Heeren J;Enrich C;Rentero C;Grewal T
通讯作者：
Grewal T
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
DOI：
10.1146/annurev-anthro-102215-100036
发表时间：
2016-01-01
期刊：
ANNUAL REVIEW OF ANTHROPOLOGY, VOL 45
影响因子：
--
作者：
Bolnick, Deborah A.;Raff, Jennifer A.;Miro-Herrans, Aida T.
通讯作者：
Miro-Herrans, Aida T.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y