RoL: FELS: EAGER: Collaborative Research: Genomics of exceptions to scaling of longevity to body size

RoL：FELS：EAGER：合作研究：长寿与体型比例的例外基因组学

• 批准号: 1838283
• 负责人: David Ray
• 金额: $ 15.19万
• 依托单位: Texas Tech University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1838283&HistoricalAwards=false
• 关键词: RoL; FELS; EAGER; Collaborative; Research

In mammals, as body size increases so does maximum lifespan, but bats represent an exception to this rule. This project will use a detailed genomic analysis to examine how bats live significantly longer than expected. Bat species studied to date can live up to six times longer than expected based on their body mass. Achieving unusually long life requires enhanced cell and tissue upkeep, maintaining immune function, and avoiding mutations that cause cancer and other age-related diseases. Hence, their exceptionally long lives require that bats evolve mechanisms to enable these features. To discover the genetic basis of healthy old age, this project focuses on pairs of closely related bat species that sharply differ in their longevity. Detailed genome comparisons between closely related species with different life spans will test different theories of aging. Although genome sequences are available for many mammals, including some bats, in most cases these are too incomplete to allow detailed comparisons. For this reason, the project also seeks to combine modern DNA sequencing techniques to produce genome sequences at greater resolution and lower cost than hitherto possible. The resulting methods can be applied across many other mammals, and vertebrates more generally. The project will also support the production of new teaching materials on evolutionary biology for secondary school students and research experiences for teachers, as well as the development of new research and analytical approaches for use by the scientific community.The scaling of longevity by body size relates the biology of populations to the molecular mechanisms of cells and tissues making up individuals, but the nature of the connections is debated. Some theories suggest that aging is the result of genetic trade-offs imposed by the diminishing chances of reproduction of older individuals (Evolutionary Theory), while others propose that aging results from molecular and cellular damage as organisms move through life (Damage Theory). This project will test these broad theories through comparative analyses of high-quality genome sequences. Besides generating at least five high quality mammalian genomes to complement existing or ongoing ones, the project will relate longevity phenotypes to genotypes across the genome sequence including genes, pseudogenes, transcription factors, and variation in the number of copies of certain genes. Coupled with analyses of genomic methylation and RNA transcripts, the project will identify candidate regions underlying divergent longevities, enabling future functional analyses at the scale of tissues, cells, and molecules.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在哺乳动物中，随着身体尺寸的增加，最大寿命也会增加，但蝙蝠是这一规则的例外。该项目将使用详细的基因组分析来研究蝙蝠如何比预期寿命长得多。迄今为止研究的蝙蝠物种的寿命比根据它们的体重预期的要长六倍。要获得异常长的寿命，需要增强细胞和组织的保养，维持免疫功能，避免导致癌症和其他与年龄有关的疾病的突变。因此，它们特别长的寿命要求蝙蝠进化出能够实现这些特征的机制。为了发现健康老年的遗传基础，该项目将重点放在寿命差异很大的密切相关的蝙蝠物种上。在具有不同寿命的密切相关物种之间进行详细的基因组比较将检验不同的衰老理论。尽管许多哺乳动物（包括一些蝙蝠）的基因组序列是可用的，但在大多数情况下，这些序列太不完整，无法进行详细的比较。为此，该项目还寻求将现代DNA测序技术联合收割机结合起来，以比迄今为止更高的分辨率和更低的成本生产基因组序列。由此产生的方法可以应用于许多其他哺乳动物，更普遍的是脊椎动物。该项目还将支持为中学生编写关于进化生物学的新教材，为教师提供研究经验，以及开发供科学界使用的新的研究和分析方法，将人口的生物学与构成个人的细胞和组织的分子机制联系起来，以身体大小衡量寿命，但这种联系的性质仍有争议。一些理论认为，衰老是老年人生殖机会减少所带来的遗传权衡的结果（进化论），而另一些理论则认为衰老是生物体在生命过程中分子和细胞损伤的结果（损伤理论）。该项目将通过对高质量基因组序列的比较分析来检验这些广泛的理论。除了生成至少五个高质量的哺乳动物基因组以补充现有或正在进行的基因组之外，该项目还将把长寿表型与基因组序列中的基因型联系起来，包括基因、假基因、转录因子和某些基因拷贝数的变化。结合基因组甲基化和RNA转录物的分析，该项目将确定潜在的不同寿命的候选区域，使未来的功能分析在组织，细胞和分子的规模。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

项目成果

A High-Quality Reference Genome Assembly of the Saltwater Crocodile, Crocodylus porosus, Reveals Patterns of Selection in Crocodylidae

• DOI: 10.1093/gbe/evz269
• 发表时间: 2020-01-01
• 期刊: GENOME BIOLOGY AND EVOLUTION
• 影响因子: 3.3
• 作者: Ghosh, Arnab;Johnson, Matthew G.;Ray, David A.
• 通讯作者: Ray, David A.

Simultaneous TE Analysis of 19 Heliconiine Butterflies Yields Novel Insights into Rapid TE-Based Genome Diversification and Multiple SINE Births and Deaths

对 19 只 Heliconiine 蝴蝶进行同步 TE 分析，对基于 TE 的基因组快速多样化和多个 SINE 出生和死亡产生新的见解

• DOI: 10.1093/gbe/evz125
• 发表时间: 2019
• 期刊: Genome Biology and Evolution
• 影响因子: 3.3
• 作者: Ray, David A;Grimshaw, Jenna R;Halsey, Michaela K;Korstian, Jennifer M;Osmanski, Austin B;Sullivan, Kevin A;Wolf, Kristen A;Reddy, Harsith;Foley, Nicole;Stevens, Richard D
• 通讯作者: Stevens, Richard D

Identification and characterization of microRNAs (miRNAs) and their transposable element origins in the saltwater crocodile, Crocodylus porosus

• DOI: 10.1016/j.ab.2020.113781
• 发表时间: 2020-08-01
• 期刊: ANALYTICAL BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Ghosh, Arnab;Platt, Roy N., II;Ray, David A.
• 通讯作者: Ray, David A.