Christine M. Drea - US grants

Traditionally, androgens have been linked with male development and estrogens with female development; yet, both classes of steroids are functionally significant in both sexes, with dramatic implications for sexual differentiation, reproductive development, and social behavior. In contrast to studies on the role of estrogens in males, the role of androgens in vertebrate females generally has been overlooked. A notable exception involves a series of studies examining androgen function in the female spotted hyena (Crocuta crocuta) - research that has challenged our assumptions of traditional sex roles and revealed a set of previously unknown mechanisms of hormonal regulation in females. Using the hyena as a predictive model, the specific aim here will be to address basic mechanisms of biobehavioral development in the ringtailed lemur (Lemur catta), an endangered prosimian primate endemic to Madagascar. The selection of L. catta as the subject of this proposal is based on the existence of a set of male-like characteristics in the female, including exaggerated or 'masculinized' external genitalia, size monomorphism with the male, and aggressively mediated social dominance over males. The proposed research will compare females against males to (1) fully characterize the suite of male-like traits in the female, (2) examine the hormonal correlates and developmental processes of those traits, and (3) explore the social factors influencing the behavioral expression of sex differences, particularly during aggression, play, and scent marking. As a nontraditional animal model, the ringtailed lemur presents an invaluable opportunity to examine current theories of sexual differentiation, to explore the role of androgens in mediating female aggressive behavior, and to elucidate the biological mechanism associated with the evolution of a female-driven social system in primates. The results of this research are likely to raise provocative questions about the traditional focus on male-driven mechanisms at the expense of considering female social and reproductive control. The findings may also suggest a broader role for androgens in female mammals and may ultimately contribute to reformulating the theory of sexual differentiation to better reflect active processes in feminine development.
The broader impact of this project will be attained primarily through a strong commitment to undergraduate and graduate training. Through hands-on research participation that fosters new collaborations and interdepartmental partnerships, this project will provide a venue for encouraging under-represented groups, particularly women, to pursue careers in science. By sharing information with the Duke University Primate Center's on-site educational program, that targets universities, primary schools, and the general public, this project will contribute to the mission of enhancing education and raising public awareness about lemurs. Moreover, any knowledge gained on lemur reproduction could ultimately benefit species conservation efforts.

Olfactory signals are ubiquitous among mammals and serve to advertise quality, reproductive state, and resource ownership to potential competitors or mates. Olfaction is an area of growing interest, but its role in primates, including humans, remains poorly understood. This project will examine olfactory communication in two key species, the ringtailed lemur and mandrill, selected because their exceptional morphological and behavioral characteristics provide an ideal comparative framework for examining olfactory mechanisms of mate choice: Both species have scent glands, but differ dramatically in their social organization and degree of sexual dimorphism. As a nontraditional model, the mandrill also promises to underscore the importance of chemosignals in Old World primates. This project also will survey odorant production in 20 other prosimian species, selected because the diversity of their scent glands and marking behavior offers an equally invaluable opportunity to examine species differences in signal content, with the goal of better understanding phylogenetic patterns. Combined field and laboratory approaches will include (1) chemical analyses to decipher the volatile information content of signals, (2) behavioral observation and bioassays to evaluate the receiver's response to scent signals, (3) genetic analyses to characterize variation in heterozygosity, relatedness, and immunocompatibility between signal senders and their recipients, and (4) proteomic analyses to unravel the nonvolatile contribution to odor cues. This integrative study will identify important correlates of olfactory cues to elucidate the biological mechanisms underlying the evolution of olfactory communication. While focused on primates, the results promise to be broadly applicable, providing additional insight into the role of olfactory signals in mammalian reproductive advertisement, social stratification, and mate choice, as well as in individual, kin, and species recognition.
The broader impact of this project will be attained through a strong commitment to teaching and an emphasis on collaboration. This project will (1) provide opportunities for training future scientists; (2) encourage under-represented groups to pursue science careers; (3) foster interdepartmental, inter-university, and international partnerships through new research ventures that broaden the perspectives of faculty and students alike; (4) integrate project-derived information into course development; (5) disseminate information to the scientific community; and (6) share information with educational programs that target universities, primary schools, and the general public, thereby enhancing education, raising public awareness about endangered primates, and aiding in species preservation.

Cooperative breeding is of significant interest in evolutionary biology and the relevance of female-female competition to the operation of sexual selection is gaining appreciation; yet, the determinants of reproductive status (breeder vs. helper) in cooperative systems and the mechanisms underlying female aggression remain poorly understood. From evidence of reproductive suppression, eviction, and infanticide, it is clear that social dominance plays a key role in female competition. What remains unclear, however, are the factors that influence which females become dominant. This project examines the proximal endocrine, social, and olfactory mechanisms that contribute to rank acquisition and reproductive skew in the cooperatively breeding meerkat of the South African Kalahari Desert. Using an integrated approach that combines hormonal, morphological, behavioral, and chemical analyses, this project will chart the developmental trajectory of female meerkats from conception to post dispersal, spanning three life stages (the fetal period, juvenility, and adulthood). It will examine the factors that are normally associated with acquisition and expression of female dominance and will test if female 'masculinization' through prenatal androgen exposure influences those factors. Integrating the information obtained across measures, life stages, treatment groups, and long-term ecological data will provide valuable insight into the development, maintenance, and signaling mechanisms of social and reproductive inequity to potentially reveal a novel mechanism in the evolution of cooperation and female reproductive skew.
The project's broader impacts derive from (1) training undergraduates, graduates, and postdoctoral associates, especially from underrepresented groups, (2) fostering interdepartmental and international collaborations, and (3) increasing education and public awareness. The latter will be achieved by involving all team members in the communication and dissemination of scientific findings, partnering with Earthwatch, contributing new information to documentaries and websites (Friends of the Kalahari Meerkat Project) aimed for the general public, schools, and researchers, and contributing to and expanding participation in field courses.

In vertebrates, genetic diversity influences many elements of an individual's fitness, such as health, survival, and reproduction. 'Inbred' individuals with less genetic diversity have greater parasite loads, reduced survivorship, and produce fewer surviving offspring than do more genetically diverse, or 'outbred" individuals - a phenomenon called inbreeding depression. Beyond these individual costs, inbreeding depression also has negative consequences on populations and species; therefore, understanding how genetic diversity impacts fitness has significant implications for conserving endangered species. Primates are especially vulnerable to inbreeding depression because of their long lifespans and low reproduction rates, yet thus far, no study has investigated how the loss of genetic diversity affects the health, survival, and reproduction of a wild primate population.

The challenge remains to identify the specific genes that can serve as estimates of 'genetic quality' because they influence variation in individual health, survival, and reproduction. One protein-coding region likely to contribute to individual differences is the Major Histocompatibility Complex (MHC). This family of genes controls the immune system's ability to recognize bacteria, viruses, and parasites, and thus, plays an essential role in the survival of an individual and their offspring.

To examine how MHC impacts fitness in a threatened primate, the ring-tailed lemur (Lemur catta), doctoral student Kathleen Grogan (Duke University), under the supervision of Dr. Christine Drea, will compare MHC diversity against survival, reproductive success, and health across an environmental stressor in a wild population at Beza Mahafaly Special Reserve, Madagascar. Survival and reproductive success, measured using long-term census data, and health, measured as parasite prevalence, diversity, and burden in fecal samples collected (a) under 'typical' environmental conditions and (b) following a severe drought, will be compared against MHC diversity. By examining the relationship between genetic diversity and fitness in wild ring-tailed lemurs, this research tests how individual differences in MHC diversity influence that individual's health, survival, and reproduction. This award will support the training of a graduate student. Additionally, the genetic information will inform conservation efforts.

Female social dominance (FSD) over males characterizes most Malagasy lemurs, which represent almost 30% of all primates; yet, little is known about the evolution or mechanism of this unusual phenomenon. Associated with FSD is a suite of behavioral, physiological, and morphological traits in females that implicates (as a possible mechanism) 'masculinization' via androgen exposure. In light of this association, this project by doctoral student Joseph Petty (Duke University), under the guidance of Dr. Christine Drea, takes a comparative and integrative approach to investigating the role of the neuroendocrine system, particularly androgens, in regulating FSD in lemurs. Studying mixed-sex pairs of six closely related Eulemur species that express a gradient of behavioral variation, from aggressive FSD to co-dominance between the sexes, this project will characterize the expression of intersexual dominance, affiliation, and aggression for each species. It will further provide novel information about the neuroendocrine correlates of behavior through the analysis of blood samples for the steroid hormones androstenedione (A4), testosterone (T), and estradiol (E2), as well as the neurotransmitter serotonin (5-HT). Lastly, to provide evidence of a direct causal linkage across species between behavior associated with FSD and neuroendocrine networks, the endocrine system will be experimentally manipulated, using a gonadotrophin-releasing hormone antagonist (antide), to assess the behavioral and social effects on masculinized behavior in female lemurs.

This project's unique comparative and experimental perspective will provide an increased understanding of the evolution of female dominance in primate social systems, as well as insight into the direct activational role of naturally circulating hormones in the regulation of female behavior. Its nontraditional focus has the potential to help update current definitions of sexual selection to better reflect the importance of intrasexual competition in females and to transform current understanding of the proximate mechanisms that underlie the physiology and expression of social dominance.

This project will be conducted at the Duke Lemur Center in Durham, NC, where it provides opportunities for collaborations with research, technical, and educational staff. Through these collaborations, this project facilitates mentorship of undergraduate researchers, dissemination of information relevant to lemur biology and conservation, public outreach, and hands-on science experience for children.

Many animals leave their birth places as they become adults to avoid competing or mating with relatives. However, traveling to and settling in a new area can be dangerous as animals are exposed to new diseases, predators, and unfriendly neighbors. This project is to identify the qualities that help these animals along the way, and to test whether those that are better able to withstand disease and to cope with stress are more successful. The research team will use sophisticated GPS technology to monitor the health and survival of young female Meerkats in the Kalahari Desert as they move from one social group to another. The project will also train undergraduate students and engage schoolchildren in the research through popular media and the Friends of Kalahari website. In addition to advancing our knowledge of dispersal, the results of this study will inform the ways in which we manage animals in fragmented and changing habitats.

In previous work on meerkat societies, the PIs found that dominant females, which are hormonally "masculinized", have the weakest constitutive immune responses of all group members, indicating a cost of androgen exposure in females. Moreover, because androgen concentrations vary with female social status, the PIs found evidence for organizational effects of differential prenatal androgen exposure on the health of juvenile offspring derived from dominant control (DC), subordinate control (SC), and dominant treated (DT) dams receiving an androgen-receptor blocker. Here, the PIs will follow the daughters of DC, SC, and DT dams over the next life-history stage "dispersal" to study the transgenerational effects of maternal social status/prenatal T on offspring dispersal. Using an integrated approach that combines behavioral, hormonal, and immunological analyses with novel global positioning system (GPS) telemetry data, the PIs will chart the health and social trajectories of daughters over successive stages of dispersal (during emigration from the natal group, a transience period, and settlement in a new territory). Specifically, the PIs will (1) determine dominance relationships and identify likely dispersers via regular behavioral observation; (2) fit GPS radio collars to 25 pre-dispersal females and chart their movements on an hourly basis; (3) measure immunocompetence (parasite burden and immune response) and hormone concentrations (androgens and glucocorticoids) in (a) fecal samples (collected prior to, over the course of, and following dispersal) and (b) serum samples (collected pre-dispersal and post-settlement); and (4) evaluate the health and survival of these females in their newly formed groups.