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

荷尔蒙睾丸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，雄性也恰好比雌性更大。然而，在雌性体型较大的几种蜥蜴物种中，睾丸激素会抑制生长。这提出了一种有趣的可能性，即在进化过程中，睾丸素(和其他激素)对生长和其他过程的影响可能会发生很大变化，而不是与生俱来。这个项目将在蜥蜴物种的荷尔蒙调节生长过程中测试这种“进化逆转”。这些物种被选中，以跨越雄性体型较大的物种和雌性体型较大的物种之间的反复进化转变。通过同时表征睾酮对数千个基因表达的影响，该项目还将确定这种荷尔蒙调节生长的“进化逆转”是如何在基因水平上完成的。这项合作研究的结果将扩大对内分泌系统的理解。它还可能通过研究密切相关的物种如何对相同的激素进化出不同的反应，来挑战从传统动物模型得出的普遍结论。该项目还将有助于满足国家的教学需求，并将让高中教师参与密集暑期项目的研究经验。正在为一名博士后研究员、一名博士和一名硕士研究生以及两名本科生提供研究培训机会。这个合作项目解决了当前比较内分泌学中存在争议的一个问题：高度保守的脊椎动物内分泌系统是否倾向于限制适应，或者荷尔蒙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。这个项目将结合激素操作和高通量RNA测序，目的是(1)通过对三种局部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着年龄、组织和激素处理的不同而不同，(2)通过将这些方法扩展到更广泛的、系统发育信息丰富的相关蜥蜴物种的样本，测试生长和基因表达的激素调节的进化逆转，这些蜥蜴物种的身体大小具有不同的性别二态模式(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的特异性是否也释放编码序列本身以更快地进化。这项研究将支持东部围栏蜥蜴最近测序的基因组作为比较内分泌学和进化遗传学领域的新兴资源的发展。该项目通过教师研讨会和教师奖学金促进科学教育工作者的专业发展，该教师研讨会和教师奖学金是通过一个持续的教育计划管理的，该计划促进了教师与科学家的合作和在K-12课堂上真正的科学发现。此外，每年为一名博士后、一名博士后、一名硕士研究生和两名本科生提供研究培训机会和资金。该奖项由综合组织系统部门的生理机制和生物力学项目、环境生物学部门的进化过程项目和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NSF的法定使命，并通过使用基金会的智力优势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.