The adaptive variation of human skin: A comprehensive anthropological genetics examination of epidermal differentiation complex

人类皮肤的适应性变异：表皮分化复合体的综合人类学遗传学检查

• 批准号: 1714867
• 负责人: Omer Gokcumen
• 金额: $ 37.79万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1714867&HistoricalAwards=false
• 关键词: adaptive; variation; human; skin; comprehensive

Skin is one of the most visible and distinguishing characteristics of humans, and understanding skin variation among humans is of central importance to the field of human biology. Indeed, there have been great advances in the last decade with regards to the genetic and developmental bases of pigmentation of the skin, explaining variation of skin color within and among human populations. However, variation in other important properties of skin, especially its barrier function, has not been well characterized. This proposal uses state-of-the-art genomic approaches to determine the extent and evolutionary relevance of skin barrier variation and address why potentially detrimental variants remain in human populations. The proposed study is at the forefront of applying novel genomic and computational technologies to anthropological questions. Specific courses and workshops are designed within the context of this project to create a major hub for training the next generation of biological anthropologists, both at the undergraduate and graduate levels. In addition, with constant public interaction, the research contributes to a better understanding of how biological evolution of the skin is independent of the cultural constructs of identity.Recently available modern and ancient genomes allow for a comprehensive look at the evolutionary signatures in the human genome. In addition, long-read sequencing technologies now permit accurate investigation of genomic structural variants (e.g., deletions and duplications of DNA segments), which have an outsized impact on human evolution and biological variation. The proposed study uses these newly available resources to investigate the evolution of the epidermal differentiation complex, a 2Mb region on human chromosome 1, which harbors more than 50 genes with known roles in skin development and function. The genes in this complex are involved in several important functions, such as immune response, insulation from UV light, heat, moisture, and wound healing. Preliminary work indicates the presence of multiple geography-specific adaptive forces, including pathogenic pressures, shaping the genetic variation in this region, providing a glimpse of the evolution of skin barrier function in humans. The proposed project expands on this premise, to provide the most comprehensive understanding to date of the evolutionary forces acting on epidermal differentiation complex genes. In addition, the project identifies genetic variants that are of anthropological significance for human skin phenotypic variation, and are thus perfect targets for downstream functional studies. The project will also lay a methodological groundwork for future anthropological genetic studies, especially pertaining to structural variation in the human genome.

皮肤是人类最明显和最显著的特征之一，了解人类皮肤的变化对人类生物学领域至关重要。事实上，在过去十年中，关于皮肤色素沉着的遗传和发育基础有了很大的进展，解释了人类种群内部和人群之间肤色的变化。然而，皮肤其他重要特性的变化，特别是其屏障功能，尚未得到很好的表征。本提案使用最先进的基因组方法来确定皮肤屏障变异的程度和进化相关性，并解决为什么潜在的有害变异仍然存在于人类群体中。提出的研究是在前沿应用新的基因组和计算技术，以人类学的问题。在这个项目的范围内设计了具体的课程和讲习班，以建立一个主要的中心，在本科和研究生两级培训下一代生物人类学家。此外，随着不断的公众互动，这项研究有助于更好地理解皮肤的生物进化如何独立于身份的文化建构。最近可用的现代和古代基因组允许对人类基因组的进化特征进行全面的观察。此外，长读测序技术现在可以精确地调查基因组结构变异（例如，DNA片段的缺失和复制），这对人类进化和生物变异有巨大的影响。该研究利用这些新获得的资源来研究表皮分化复合体的进化，表皮分化复合体是人类1号染色体上一个2Mb的区域，包含50多个已知在皮肤发育和功能中起作用的基因。这个复合体中的基因参与了几个重要的功能，如免疫反应、隔绝紫外线、热、湿和伤口愈合。初步研究表明，多种地理特异性适应力量的存在，包括致病压力，塑造了该地区的遗传变异，为人类皮肤屏障功能的进化提供了一瞥。该项目在此前提下进行扩展，以提供迄今为止最全面的理解作用于表皮分化复杂基因的进化力量。此外，该项目还确定了对人类皮肤表型变异具有人类学意义的遗传变异，因此是下游功能研究的完美目标。该项目还将为未来的人类学遗传研究，特别是与人类基因组结构变异有关的研究奠定方法学基础。

项目成果

Analysis of Haplotypic Variation and Deletion Polymorphisms Point to Multiple Archaic Introgression Events, Including from Altai Neanderthal Lineage

• DOI: 10.1534/genetics.120.303167
• 发表时间: 2020-06-01
• 期刊: GENETICS
• 影响因子: 3.3
• 作者: Taskent, Ozgur;Lin, Yen Lung;Gokcumen, Omer
• 通讯作者: Gokcumen, Omer

Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots

• DOI: 10.1093/gbe/evz058
• 发表时间: 2019-04-01
• 期刊: GENOME BIOLOGY AND EVOLUTION
• 影响因子: 3.3
• 作者: Lin, Yen-Lung;Gokcumen, Omer
• 通讯作者: Gokcumen, Omer

The Impact of Ancient Genome Studies in Archaeology

古代基因组研究对考古学的影响

• DOI: 10.1146/annurev-anthro-010220-074353
• 发表时间: 2020
• 期刊: Annual Review of Anthropology
• 影响因子: 2.8
• 作者: Gokcumen, Omer;Frachetti, Michael
• 通讯作者: Frachetti, Michael

Shades of complexity: New perspectives on the evolution and genetic architecture of human skin

• DOI: 10.1002/ajpa.23737
• 发表时间: 2019-01-01
• 期刊: AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY
• 影响因子: 2.8
• 作者: Quillen, Ellen E.;Norton, Heather L.;Jablonski, Nina G.
• 通讯作者: Jablonski, Nina G.

Archaic hominin introgression into modern human genomes

• DOI: 10.1002/ajpa.23951
• 发表时间: 2019-11-08
• 期刊: AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY
• 影响因子: 2.8
• 作者: Gokcumen, Omer