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

睾酮激素通常被认为是生长的促进剂，但这种推广是基于医学、农业和水产养殖中的模式物种。在大多数这些模式物种中，雄性碰巧也比雌性大。然而，在一些雌性体型较大的蜥蜴物种中，睾酮抑制了它们的生长。这就提出了一种有趣的可能性，睾酮（和其他激素）对生长和其他过程的影响远非与生俱来，而是在进化过程中发生了相当大的变化。这个项目将在蜥蜴物种生长的激素调节中测试这种“进化逆转”。这些物种被选择来跨越雄性体型较大和雌性体型较大的物种之间的反复进化转变。通过同时描述睾酮对数千种基因表达的影响，该项目还将确定激素调节生长的这种“进化逆转”是如何在遗传水平上完成的。这项合作研究的结果将扩大对内分泌系统的认识。通过研究亲缘关系密切的物种如何进化出对同一种激素的不同反应，它也可能挑战传统动物模型得出的结论。该项目还将有助于满足国家的教学需求，并将在一个密集的暑期项目中让高中教师参与研究经验。提供博士后1人、博士研究生1人、硕士研究生1人、本科生2人的研究培训机会。这个合作项目解决了比较内分泌学中当前争论的一个问题：高度保守的脊椎动物内分泌系统是否倾向于限制适应，或者激素与基因网络耦合的关键进化变化是否反而促进了快速进化。该项目将结合激素操作和高通量RNA测序，旨在(1)通过对三种焦点蜥蜴物种的详细实验，描述生长调节基因网络在年龄、组织和激素治疗方面的表达差异；(2)通过将这些方法扩展到更广泛的领域，测试生长和基因表达激素调节的进化逆转。从系统发育的角度，对具有不同体型性别二态性（雄性较大或雌性较大）的相关蜥蜴物种进行取样，并(3)对数千种表达基因的序列进化速率进行表征，以测试由激素调节实现的表达特异性是否也使编码序列本身能够更快地进化。这项研究将支持最近测序的东部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来促进科学教育者的专业发展，该项目通过持续的教育计划来促进教师与科学家的合作和K-12课堂上真正的科学发现。此外，每年还为一名博士后、一名博士生、一名硕士和两名本科生提供研究培训机会和资金。该奖项由综合有机体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以及生物科学理事会新兴前沿项目的生命规则风险基金共同资助。该奖项反映了美国国家科学基金会的法定使命，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。

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.