<p>Humans are natural politicians. We obsessively collect social information that is both observable (e.g., about third-party relationships) and unobservable (e.g., about others’ psychological states), and we strategically employ that information to manage our cooperative and competitive relationships. To what extent are these abilities unique to our species, and how did they evolve? The present dissertation seeks to contribute to these two questions. To do so, I take a comparative perspective, investigating social decision-making in humans’ closest living relatives, bonobos and chimpanzees. In Chapter 1, I review existing literature on theory of mind—or the ability to understand others’ psychological states—in these species. I also present a theoretical framework to guide further investigation of social cognition in bonobos and chimpanzees based on hypotheses about the proximate and ultimate origins of their species differences. In Chapter 2, I experimentally investigate differences in the prosocial behavior of bonobos and chimpanzees, revealing species-specific prosocial motivations that appear to be less flexible than those exhibited by humans. In Chapter 3, I explore through decision-making experiments bonobos’ ability to evaluate others based on their prosocial or antisocial behavior during third-party interactions. Bonobos do track the interactions of third-parties and evaluate actors based on these interactions. However, they do not exhibit the human preference for those who are prosocial towards others, instead consistently favoring an antisocial individual. The motivation to prefer those who demonstrate a prosocial disposition may be a unique feature of human psychology that contributes to our ultra-cooperative nature. In Chapter 4, I investigate the adaptive value of social cognition in wild primates. I show that the recruitment behavior of wild chimpanzees at Gombe National Park, Tanzania is consistent with the use of third-party knowledge, and that those who appear to use third-party knowledge receive immediate proximate benefits. They escape further aggression from their opponents. These findings directly support the social intelligence hypothesis that social cognition has evolved in response to the demands of competing with one’s own group-mates. Thus, the studies presented here help to better characterize the features of social decision-making that are unique to humans, and how these abilities evolved.</p> / Dissertation

Great ape gesture is an elaborate, flexible system of intentional communication. It has been suggested that human language originated in gesture, thus, the gestural communication of great apes is of great interest for questions on the origin of language. To date, systematic studies of great ape gesture have been limited to restricted captive settings, supplemented by the study of a few specific gestures in wild populations. To address questions about gestural communication from an evolutionary perspective it is necessary to extend the systematic study of gesture into a wild ape population. I therefore undertook a 22-month study of gesture in the wild Sonso chimpanzee community in Budongo, Uganda. Sonso chimpanzees employ a large repertoire of species-typical gestures in intentional communication; a proportion of this repertoire appears to be ape-typical, as would be expected with a biologically given trait. Chimpanzees can acquire new behavioural patterns through imitation; however, this apparently does not represent a significant means of acquiring gestures. Gesturing was employed regularly in an intentional manner from the end of the first year, and was used by chimpanzees of all ages to communicate across a range of contexts, including the evolutionarily urgent context of consortship. Immature chimpanzees used a wide range of gestures, which they combined into rapid sequences. With maturity, use of the repertoire was ‘tuned’ to focus on the most effective gestures, which were then used individually. Despite the evidence for referential pointing in captive chimpanzees, there was little evidence for the regular use of it in wild chimpanzees. Gestures were used to communicate a range of imperative requests that regulated social behaviour. Chimpanzee gestures vary from the ambiguous to the highly specific in meaning; and, while gestures were used flexibly, they tended to be associated with a single dominant meaning.

GB virus C (GBV-C) is a nonpathogenic lymphotropic virus that replicates in B and T lymphocytes. Infection with GBV-C is documented worldwide and is common: between 1% and 5% of healthy blood donors are viremic at the time of donation. Antibodies to GBV-C proteins are not usually detected during viremia, and antibodies to the GBV-C envelope glycoprotein E2 develop following the clearance of viremia. Although GBV-C viremia may persist for decades, viremia usually clears within 2 years following infection in the majority of individuals infected by blood transfusion. A chimpanzee variant of GBV-C, designated GBV-Ccpz, is found in captive and noncaptive chimpanzees and its prevalence and natural history are uncharacterized. GBV-C research was initially performed by viral hepatitis research groups because it was predicted to cause hepatitis. The realization that GBV-C did not cause hepatitis resulted in a marked reduction in research activity. Because Hepatitis C virus co-infection worsens the clinical course of HIV-infected patients, researchers hypothesized that the related virus, GBV-C, may impact HIV disease. In 1998, researchers found that HIV-infected individuals who were co-infected with GBV-C survived longer than those without GBV-C. These findings provide the rationale for examining the relationship of GBV-C and HIV and the development of GBV-C as a novel therapeutic for HIV. GBV-C infection of PBMCs inhibits the replication of HIV isolates and one of the mechanisms for this is the induction of the release of soluble ligands for HIV entry receptors (RANTES, macrophage inflammatory proteins (MIP)-1α and MIP-1β and SDF-1) by GBV-C. The GBV-C envelope glycoprotein E2 contributes directly to the inhibition of HIV infection. Incubation of recombinant E2 with PBMCs at 4°C prior to HIV infection results in a decrease in HIV replication, and only HIV gp160 enveloped pseudoparticle transduction, not VSV-G enveloped pseudoparticle transduction, is inhibited by GBV-C E2. This suggests that GBV-C E2 inhibits HIV infection at an entry step when the HIV gp160 envelope protein interacts with cellular receptors and membranes. How GBV-C E2 interacts with cellular surfaces and which cellular proteins are utilized for GBV-C binding and entry are unknown. Here, we characterize GBV-C E2 binding to human PBMCs, murine cells, and multiple transformed cell lines to identify the PBMC subset which E2 binds and to identify candidate cellular receptors involved in GBV-C binding and entry. Understanding how GBV-C E2 interacts with cellular surfaces is critical to determining how it inhibits HIV entry. Anti-GBV-C E2 antibodies are also associated with improved survival in HIV-infected individuals. Recent studies demonstrated that anti-E2 antibodies neutralize HIV infection in vitro and immunoprecipitate HIV virions. In these studies, we describe how anti-E2 antibodies immunoprecipitate retroviral particles regardless of the specific viral envelope protein on the surface, but only neutralize particles bearing the HIV gp160 envelope protein. We also found that the cellular antigen recognized by anti-E2 antibodies is accessible only in permeabilized cells and not on the cell surface. These studies provide insight into the HIV-inhibitory mechanisms of anti-E2 antibodies, which should aid in the development of GBV-C E2 as an immunogen in an HIV vaccine. Finally, no animal models exist for studying GBV-C infection or GBV-C vaccines as HIV therapeutics in vivo. We examined the natural history GBV-Ccpz in a captive chimpanzee population, and found that the prevalence of GBV-Ccpz viremia and anti-E2 antibodies, as well as the length of persistent infection, were similar to those found in healthy human blood donors. The GBV-Ccpz 5#8217;ntr and RdRp sequences from chimpanzee subspecies troglodytes and verus shared a high level of sequence identity and indicate that the chimpanzee variant should be designated GBV-Ccpz rather than the currently used GBV-Ctrog. These findings demonstrate that GBV-Ccpz viremia and E2 antibody status should be tested in animals involved in clinical research trials because affected animals may have altered responses to GBV-C infection or HIV vaccines, and that the chimpanzee would be a good animal model in which to study GBV-C infection.

<p>What makes our minds human? How did they evolve to be this way? This dissertation presents data from two complementary lines of research driven by these orienting questions. The first of these explores the `what' of human cognitive evolution through comparative studies with chimpanzees and bonobos. The general aim of these studies is to understand which aspects of cognition are unique to humans, and which are shared with our closest living relatives. Chapters 2-3 test the hypothesis that humans have unique cognitive skills for reasoning about the attention of other individuals (theory of mind), and unique motivation to use these skills in cooperative contexts with conspecifics. In Chapter 2 I show that understanding others' attention is unlikely to be the `small difference that makes the big difference', as some researchers have proposed. However, my data support the possibility that species differences in the ontogeny of these skills may have robust consequences for the adult cognitive phenotype. In Chapter 3 I show that (contrary to previous reports) nonhuman apes are also motivated to engage in some simple triadic social activities, which resemble those characteristic of human children. Again however, I identify important differences between humans and other apes in their spontaneous preferences for these types of activities, and their attitudes toward a partner when cooperative behaviors are interrupted. The second half of this dissertation (Chapters 4-5) explores the `why' and `how' of cognitive evolution. Chapter 4 outlines the kind of research questions and methods that comparative psychologists will need to embrace in order to use the comparative method to its full potential in the study of cognitive evolution. Chapter 5 provides a proof of principle for this approach using a dataset including 33 species tested on two cognitive tasks measuring inhibitory control. Here I show that cognitive skills for inhibitory control are closely related to phylogeny across species, and strongly predicted by absolute (but not relative) brain size. Further, I show that two of the other leading hypotheses put forth to explain primate intelligence, namely sociality and diet, do not predict cognitive skills on these tasks. These data illustrate the power of the comparative method for understanding cognitive evolution, and provide a starting point for future studies embracing this approach. Collectively, this research refines our understanding of how human cognition differs from that of other primates, and illustrates the utility of studying cognitive evolution from an explicitly phylogenetic comparative framework.</p> / Dissertation

17q23 amplicon is one of the many chromosomal regions that undergo amplification in breast tumors. Such amplicons harbor proto-oncogenes that may be overexpressed due to gene amplifications. Copy number analysis in breast cancer cell lines and breast tumors identified several independently amplified regions within the 17q23 amplicon, suggesting that a number of genes are selected for amplification as they may independently contribute to tumor formation and progression. To characterize distinct amplicons on 17q23 and localize putative oncogenes, various studies are done on this region. In order to better understand the role of 17q23 amplification in breast cancer, characterizing unidentified genes or ESTs (Expressed Sequence Tags) on the 17q23 amplicon is crucial. In this study, in silico analysis of human (H.sapiens), chimpanzee (P.troglodytes), and mouse (M.musculus) genomes were performed to examine sequence homology between these 3 species for the purpose of identifying novel genes. The objective of this study was to analyze a 50 kb region between TBX2 and TBX4 genes and characterize the EST T02811 located on that region. Analysis and comparisons of these three genomes were established based on genomic sequences and availability of ESTs with gene prediction programs (BLAST, Pipmaker, Vista, GENSCAN etc.). Based on our results, we prepared a homology map between these 3 species, including positions of ESTs that may indicate novel genes. In this 50 kb region, we found in silico and experimantal evidence for the presence of an unidentified gene. We managed to extend the 313 bp EST T02811 size to 1423 bp which we think is as of yet incomplete. Further studies are needed to characterize this novel gene as a potential oncogene candidate. Characterizing the roles of such candidate oncogenes in amplicons will provide a better understanding of genomic amplicon regions and their roles in tumorigenesis.

Key insights into the evolutionary origins of human social behavior can be gained via study of our closest living relatives, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Despite being equally related to humans, these two species differ importantly in aspects of their morphology, physiology, behavior, and cognition. Morphological comparisons reveal numerous traits in bonobos that can be viewed as paedomorphic, or juvenile, relative to chimpanzees. Meanwhile, comparisons of endocrinology in the two species suggest that aspects of steroid physiology have changed significantly in bonobos in line with their reductions in male mating competition. Based on this evidence, I tested the hypothesis that behavioral and cognitive differences between bonobos and chimpanzees derive from changes in their 1) developmental trajectories of behavioral and cognitive traits and 2) neuroendocrine influences on behavior and cognition. I tested this hypothesis by studying semi free-ranging populations of bonobos and chimpanzees. First, I found that bonobos retained juvenile levels of food sharing and social inhibition into adulthood, leading them to differ from chimpanzees in these traits as adults. Second, I found that bonobos showed muted elevations in their levels of testosterone from infancy to adulthood in comparison to chimpanzees, suggesting that numerous aspects of development differ between these two species. Third, I found that male bonobos and chimpanzees differ in their immediate neuroendocrine shifts surrounding competition, implicating changes in proximate mechanisms influencing social behavior between the two species. Fourth, I found that patterns of cognitive development in these two apes differed significantly from those of human children. These results provide substantial support for my hypothesis that phenotypic differences between bonobos and chimpanzees evolved via shifts in bonobo development and neuroendocrine physiology. More broadly, they illustrate how behavioral and cognitive evolution can occur through changes in ontogenetic trajectories and neuroendocrine mechanisms. These findings thus show the merits of integrating ultimate and proximate levels of analysis in studies of the evolution of human behavior and cognition. / Human Evolutionary Biology

Male reproductive success in many mammals depends on their ability to allocate sufficient energetic resources to mating competition. Such costs are particularly pronounced in species with high levels of sexual body dimorphism, intense polygyny and distinct breeding seasons. I tested the hypothesis that male reproductive effort incurs significant energetic costs in wild chimpanzees (Pan troglodytes), a species with moderate sexual dimorphism, promiscuous mating and lack of breeding seasonality. My field studies combined behavioral observations on male chimpanzee behavior with non-invasive sampling of urinary C-peptide (UCP). UCP is a biomarker of insulin production that indexes individual energy balance. This dissertation contributes to the understanding of UCP as an energy assay by (1) validating the application of UCP for assessing dietary quality in bonobos (Pan paniscus) at Kokolopori, DRC and (2) providing a detailed assessment of diurnal variation in UCP levels in relation to short-term changes in food intake in chimpanzees at Kanyawara, Kibale NP, Uganda. I used UCP measurements in conjunction with full-day focal observations of male chimpanzees to assess the energetic costs of male-male competition for status and mating opportunities. Data on feeding time and rates of aggression suggested that males experience a reduction in energy intake and an increase in energy expenditure when highly attractive parous females were in estrus. UCP data supported these conclusions because males had lower UCP levels on mating days, and rates of aggression were negatively associated with UCP levels. Mean daily party size was also associated with low UCP levels, controlling for the presence of estrous females. Habitat-wide availability of preferred fruits was positively associated with male rates of aggression suggesting that energy availability mediates male investment towards energetically costly competitive behaviors. Contrary to expectations males who were most successful in obtaining copulations (high-ranking males) did not suffer higher energetic costs than lower-ranking males during periods of mating competition. Costs or reproductive effort include both direct competition for matings and long-term competition over social status. Maintenance of social rank over long periods appears to be particularly important in this slow-reproducing, long-lived and nonseasonally breeding primate. / Human Evolutionary Biology

This dissertation consists of two studies: the first focuses on reliability of chimpanzee personality and subjective well-being (SWB) scores, the second on validating those scores by comparing them to subjective assessments of behavior in dyads. The first measured reliability of scores of personality and subjective well-being (SWB) across ten years. Dominance rank, and the Dominance and Extraversion Factors significantly correlated between time points. In the second study, I investigated the impact of personality, SWB, and demographic characteristics on individual variation in dyadic-level individual behavior. Age predicted likeability in females, and age and rank predicted likeability in males. Neither personality factors nor SWB were correlated to likeability. An Affable domain scale and an Agonistic domain scale were constructed from the personality items. The Affable domain scale correlated with chimpanzees who were scored high neutral in social interactions, and the agonistic scale correlated with low neutral score in social interactions.

The goal of this study was to examine several aspects of the population genetics and population biology of the Nigeria-Cameroon chimpanzee at seven sampling locations in the south of Taraba State, Nigeria. Three of the sampling locations are within GGNP and two are situated just outside the southern boundary of GGNP. The final two sampling locations are found within Ngel Nyaki forest reserve, at each of the two forest fragments inside the reserve. Ngel Nyaki forest reserve was the focus of the study and the principal goal was to 16 determine if the community of chimpanzees at Ngel Nyaki forest reserve has become isolated from the chimpanzees at GGNP using microsatellite loci extracted from non-invasive sources of DNA. In Chapter two, the methods used to extract and amplify the DNA and the protocols used to confirm the genotypes are outlined. Chapter three examines the population structure of the chimpanzees among the regions sampled in this study, particularly addressing the question as to whether the chimpanzees at Ngel Nyaki forest reserve are isolated from the chimpanzees at GGNP. Chapter four investigates patterns of sex biased dispersal in the Nigeria-Cameroon chimpanzee. In Chapter five, population viability analysis is used to determine the fate of the chimpanzees at Ngel Nyaki forest reserve under a range of management scenarios. Chapter six summarizes the conclusions of the study and presents a conservation strategy to ensure the viability of the population of chimpanzees at Ngel Nyaki forest reserve.

Transposable elements (TEs) are mobile DNA sequences that can move from one location to another in the genome. These elements encode regulatory features including transcriptional promotion and termination signals facilitating the production of new transcripts (or elements). The elements thus produced are inserted back into the genome. Due to their insertional capacity and encoded regulatory features, TEs have, in recent years, been recognized as significant contributors to regulatory variation both within and between species. In comparing the human and chimpanzee genomes it has been hypothesized that the genetic basis of the phenotypic differences that distinguish them may be the result of regulatory differences existing between the two species. Since TEs inserted in proximity to genes can significantly alter gene expression patterns, this research aims at exploring the influence of TE sequences and retrotransposons in particular in the evolution of gene regulation between humans and chimpanzees. A first systematic search of one particular class of retrotransposons - endogenous retroviruses (ERVs) was carried out in the chimpanzee genome. Forty two families of ERVs were identified in the chimpanzee genome including the discovery of 9 previously unknown families in humans. The vast majority of these families were found to have orthologs in the human genome except for two (CERV 1/PTERV1 and CERV 2) families. The two CERV families without orthologs in the human genome display a patchy distribution among primates. Nine families of chimpanzee ERVs have been transpositionally active since the human-chimpanzee divergence, while only two families have been active in the human lineage. The genomic differences [INDEL variation (80-12,000 bp in length)] between humans and chimpanzees are laid out. The INDEL variation located in or near genes is categorized in detail and is correlated with differences in gene expression patterns in a variety of organs and tissues. Results indicate that the majority of the INDEL variation between the two species is associated with retrotransposon sequences and that this variation is significantly correlated with differences in gene expression most notably in brain and testes. These findings are consistent with the hypothesis that retrotransposon mediated regulatory variation may have been a significant factor in human/chimpanzee evolution.