Collaborative Research: Evolutionary reversals in hormonal modulation of growth-regulatory gene networks

合作研究：生长调节基因网络激素调节的进化逆转

• 批准号: 1755026
• 负责人: Robert Cox
• 金额: $ 65.33万
• 依托单位: University of Virginia Main Campus
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755026&HistoricalAwards=false
• 关键词: Collaborative; Research; Evolutionary; reversals; hormonal

The hormone testosterone is classically viewed as a promoter of growth, but this generalization is based on model species in medicine, agriculture, and aquaculture. In most of these model species, males also happen to be larger than females. However, in several lizard species in which females are larger, testosterone inhibits growth. This raises the intriguing possibility that, far from being hard-wired, the effects of testosterone (and other hormones) on growth and other processes may change considerably during evolution. This project will test for such "evolutionary reversals" in the hormonal regulation of growth across lizard species. These species have been selected to span repeated evolutionary shifts between those in which males are larger and those in which females are larger. By simultaneously characterizing the effects of testosterone on the expression of thousands of genes, this project will also determine how such "evolutionary reversals" in the hormonal regulation of growth are accomplished at the genetic level. The results of this collaborative study will broaden understanding of the endocrine system. It may also challenge generalizations derived from traditional animal models by investigating how closely related species evolve different responses to the same hormone. The project will also contribute to filling national teaching needs and will involve high school teachers in research experiences in an intensive summer program. Research training opportunities are being provided for a post-doctoral fellow, a PhD and an MS graduate student, and two undergraduate students.This Collaborative project addresses an issue of current debate in comparative endocrinology: whether the highly conserved vertebrate endocrine system tends to constrain adaptation, or whether key evolutionary changes in the coupling of hormones to gene networks instead facilitate rapid evolution. This project will combine hormone manipulations and high-throughput RNA sequencing aimed at (1) characterizing how the expression of growth-regulatory gene networks differs with respect to age, tissue, and hormone treatment using detailed experiments on three focal lizard species, (2) testing for evolutionary reversals in the hormonal regulation of growth and gene expression by extending these methods to a broader, phylogenetically informed sampling of related lizard species with variable patterns of sexual dimorphism in body size (male-larger or female-larger), and (3) characterizing rates of sequence evolution for thousands of expressed genes to test whether the specificity of expression that is achieved by hormonal regulation also frees coding sequences themselves to evolve more quickly. This research will support development of the recently sequenced genome of the Eastern Fence Lizard as an emerging resource for the fields of comparative endocrinology and evolutionary genetics. This project enhances the professional development of science educators through Teacher Workshops and Teacher Fellowships administered through an ongoing education program, which fosters teacher-scientist collaboration and authentic scientific discovery in the K-12 classroom. In addition, research training opportunities and funding are provided for a post-doctoral fellow, a PhD student, a MS student, and for two undergraduates each year.This award is co-funded by the Physiological Mechanisms and Biomechanics Program in the Division of Integrative Organismal Systems, the Evolutionary Processes Program in the Division of Environmental Biology, and the Rules of Life Venture Fund of the Emerging Frontiers Program in the Directorate for Biological Sciences.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.

睾酮激素被经典地视为生长的促进剂，但这种概括是基于医学，农业和水产养殖中的模式物种。在大多数这些模式物种中，雄性也恰好比雌性大。然而，在几种雌性体型较大的蜥蜴中，睾丸激素抑制了生长。这提出了一个有趣的可能性，即睾丸激素（和其他激素）对生长和其他过程的影响可能在进化过程中发生很大变化，而不是与生俱来的。该项目将测试这种“进化逆转”在蜥蜴物种生长的激素调节。 这些物种被选择来跨越雄性更大和雌性更大之间的重复进化转变。通过同时表征睾酮对数千个基因表达的影响，该项目还将确定生长激素调节中的这种“进化逆转”如何在遗传水平上完成。这项合作研究的结果将扩大对内分泌系统的了解。 它也可能通过研究密切相关的物种如何对同一激素进化出不同的反应来挑战传统动物模型的概括。该项目还将有助于满足国家的教学需求，并将使高中教师参与密集的暑期课程的研究经验。研究培训机会正在提供给博士后研究员，博士和硕士研究生，和两名本科生。这个合作项目解决了目前比较内分泌学的争论问题：是否高度保守的脊椎动物内分泌系统往往会限制适应，或者是否关键的进化变化，激素的耦合到基因网络，而不是促进快速进化。该项目将结合联合收割机激素操作和高通量RNA测序，旨在（1）通过对三种重点蜥蜴物种的详细实验，表征生长调节基因网络的表达如何随年龄，组织和激素治疗而不同，（2）通过将这些方法扩展到更广泛的领域，具有不同体型两性异形模式的相关蜥蜴物种的遗传学信息取样（雄性-较大或雌性-较大），以及（3）表征数千个表达基因的序列进化速率，以测试通过激素调节实现的表达特异性是否也释放了编码序列本身，使其进化得更多。快这项研究将支持最近测序的东栅栏蜥蜴基因组的发展，作为比较内分泌学和进化遗传学领域的新兴资源。该项目通过教师研讨会和教师奖学金，通过一个正在进行的教育计划，促进教师与科学家的合作和真正的科学发现在K-12教室管理，提高科学教育工作者的专业发展。此外，每年还为一名博士后研究员、一名博士生、一名硕士生和两名本科生提供研究培训机会和资金。该奖项由综合有机系统部的生理机制和生物力学项目、环境生物学部的进化过程项目、该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Effects of testosterone on urogenital tract morphology and androgen receptor expression in immature Eastern Fence lizards (Sceloporus undulatus)

睾酮对未成熟东部栅栏蜥蜴（Sceloporus undulatus）泌尿生殖道形态和雄激素受体表达的影响

• DOI: 10.1016/j.ygcen.2023.114418
• 发表时间: 2024
• 期刊: General and Comparative Endocrinology
• 影响因子: 2.7
• 作者: Milnes, Matthew R.;Robinson, Christopher D.;Foley, Alexis P.;Stepp, Charleigh;Hale, Matthew D.;John-Alder, Henry B.;Cox, Robert M.
• 通讯作者: Cox, Robert M.

Evolution of hormone-phenotype couplings and hormone-genome interactions

• DOI: 10.1016/j.yhbeh.2022.105216
• 发表时间: 2022-06-28
• 期刊: HORMONES AND BEHAVIOR
• 影响因子: 3.5
• 作者: Cox，Robert M.;Hale，Matthew D.;Cox，Christian L.
• 通讯作者: Cox，Christian L.

Species differences in hormonally mediated gene expression underlie the evolutionary loss of sexually dimorphic coloration in Sceloporus lizards

激素介导的基因表达的物种差异是剑孔蜥蜴两性二态性颜色进化丧失的基础

• DOI: 10.1093/jhered/esad046
• 发表时间: 2023
• 期刊: Journal of Heredity
• 影响因子: 3.1
• 作者: Robinson, Christopher D.;Hale, Matthew D.;Wittman, Tyler N.;Cox, Christian L.;John-Alder, Henry B.;Cox, Robert M.;Bronikowski, ed., Anne
• 通讯作者: Bronikowski, ed., Anne