Project Grant 2222087

COLLABORATIVE RESEARCH: HOW TO GET SMAL: STUDYING ISLAND DWARFISM TO FIND SHARED MOLECULAR MECHANISMS ACROSS LIFE HISTORY TRAITS -MANY HUMAN AND ANIMAL TRAITS ARE COMPLEX SUCH THAT THEY ARE DEFINED BY BOTH THE ENVIRONMENT AND MANY GENES; SUCH TRAITS INCLUDE BODY SIZE AND AGE OF REPRODUCTIVE MATURITY. THE MOLECULAR MECHANISMS THAT DETERMINE THESE COMPLEX TRAITS IN NATURAL POPULATIONS ARE NOT WELL UNDERSTOOD. THE RESEARCH GOAL OF THIS PROJECT IS TO UNDERSTAND THE MECHANISMS REGULATING COMPLEX TRAITS, HOW THEY ARE ALTERED IN NATURAL POPULATIONS, AND WHAT ASPECTS OF THESE MECHANISMS ARE SHARED ACROSS SPECIES. THIS PROJECT USES THE POWER OF A NATURAL EXPERIMENT WHERE ANIMALS ISOLATED ON ISLANDS HAVE BECOME SMALL WITH ALTERED REPRODUCTION SIMILAR TO ANIMALS UNDER SELECTIVE BREEDING, SUCH AS DOGS, CATTLE, AND CHICKENS. THIS PROJECT WILL CONTRAST MAINLAND CALIFORNIA AND CALIFORNIA CHANNEL ISLAND POPULATIONS OF FIVE REPTILE SPECIES TO UNDERSTAND THE CHANGES IN THEIR GENOMES, CELLS, AND HORMONE PHYSIOLOGY THAT ALTER THEIR BODY SIZE AND REPRODUCTION ON THE ISLANDS. IN THIS PROCESS, NOVEL TOOLS WILL BE DEVELOPED TO STUDY THE GENETIC AND HORMONE PHYSIOLOGY OF REPTILES THAT CAN BE USED TO UNDERSTAND THE HEALTH OF NATURAL AND ZOO POPULATIONS TO AID CONSERVATION EFFORTS AND IN AGRICULTURE. THIS PROJECT WILL ENGAGE OVER 30 UNDERGRADUATE AND GRADUATE STUDENTS (ACROSS THREE UNIVERSITIES) AND HIGH SCHOOL TEACHERS IN THE RESEARCH AND WILL SUPPORT THE DEVELOPMENT OF TEACHING MODULES BASED ON SCIENTIFIC RESEARCH. THE FINDINGS FROM THIS RESEARCH WILL IMPROVE OUR GENERAL UNDERSTANDING OF HOW GENES AND ENVIRONMENT DETERMINE COMPLEX TRAITS, AND MORE SPECIFICALLY WILL IDENTIFY MECHANISMS REGULATING BODY SIZE AND REPRODUCTION IN NATURAL POPULATIONS THAT ARE SHARED ACROSS ANIMAL SPECIES. COMPLEX TRAITS SUCH AS BODY SIZE AND REPRODUCTION ARE INHERENTLY REGULATED BY MOLECULAR NETWORKS THAT ARE INFLUENCED BY GENETICS AND THE ENVIRONMENT, BUT THE MOLECULAR MECHANISMS OF HOW COMPLEX TRAITS ARE REGULATED IN AND SHARED ACROSS NATURAL POPULATIONS ARE NOT WELL UNDERSTOOD. UNRAVELING THESE MOLECULAR MECHANISMS WILL BE A TRANSFORMATIVE STEP IN OUR UNDERSTANDING OF HOW COMPLEX TRAITS ARE REGULATED IN ECOLOGICALLY DIVERGENT POPULATIONS. THE GROWTH HORMONE INSULIN/INSULIN-LIKE SIGNALING (GH-IIS) NETWORK HAS BEEN EXTENSIVELY STUDIED IN BIOMEDICAL LABORATORY MODELS AND ARTIFICIALLY SELECTED SPECIES, FOR ITS ROLE IN GROWTH, BODY SIZE, AND REPRODUCTION, THUS MAKING IT AN IDEAL CANDIDATE NETWORK FOR REGULATING THESE COMPLEX TRAITS IN NATURAL SYSTEMS. TO UNDERSTAND THE MECHANISTIC BASIS FOR HOW COMPLEX TRAITS CAN BE ALTERED IN NATURAL POPULATIONS AND AT WHAT LEVEL THESE MECHANISMS ARE SHARED ACROSS SPECIES, THIS PROJECT WILL CONTRAST MAINLAND AND ISLAND POPULATIONS FOR FIVE REPTILE SPECIES, THREE THAT DEMONSTRATE INSULAR DWARFISM AND TWO THAT DO NOT. DATA WILL BE INTEGRATED ACROSS MULTIPLE LEVELS OF BIOLOGICAL ORGANIZATION OF THE GH-IIS MOLECULAR NETWORK TO PURSUE THE FOLLOWING THREE AIMS: (1) QUANTIFY THE RELATIONSHIP BETWEEN GH-IIS HORMONE PHYSIOLOGY AND LIFE-HISTORY TRAITS IN NATURAL POPULATIONS; (2) EVALUATE GENETIC DIVERGENCE IN THE GH-IIS NETWORK; AND (3) QUANTIFY DIVERGENCE IN CELLULAR PHYSIOLOGY AND INTRACELLULAR SIGNALING. THIS PROJECT WILL FURTHER THE UNDERSTANDING OF WHICH NODES WITHIN THE NETWORK ARE RESPONSIVE TO ECOLOGICAL PRESSURES IN NATURAL POPULATIONS, AND WHICH ARE CONSTRAINED. THIS NEW KNOWLEDGE INTEGRATED ACROSS HIERARCHICAL LEVELS OF BIOLOGY TO IDENTIFY MECHANISTIC PRINCIPALS DEFINING COMPLEX TRAITS IN NATURAL POPULATIONS. 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.