How does cognition evolve? Phylogenetic comparative psychology.

Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

Interpreting Human Genetic Variation through Genomics and In Vivo Models

Improvements in genomic technology, both in the increased speed and reduced cost of sequencing, have expanded the appreciation of the abundance of human genetic variation. However the sheer amount of variation, as well as the varying type and genomic content of variation, poses a challenge in understanding the clinical consequence of a single mutation. This work uses several methodologies to interpret the observed variation in the human genome, and presents novel strategies for the prediction of allele pathogenicity.

Using the zebrafish model system as an in vivo assay of allele function, we identified a novel driver of Bardet-Biedl Syndrome (BBS) in CEP76. A combination of targeted sequencing of 785 cilia-associated genes in a cohort of BBS patients and subsequent in vivo functional assays recapitulating the human phenotype gave strong evidence for the role of CEP76 mutations in the pathology of an affected family. This portion of the work demonstrated the necessity of functional testing in validating disease-associated mutations, and added to the catalogue of known BBS disease genes.

Further study into the role of copy-number variations (CNVs) in a cohort of BBS patients showed the significant contribution of CNVs to disease pathology. Using high-density array comparative genomic hybridization (aCGH) we were able to identify pathogenic CNVs as small as several hundred bp. Dissection of constituent gene and in vivo experiments investigating epistatic interactions between affected genes allowed for an appreciation of several paradigms by which CNVs can contribute to disease. This study revealed that the contribution of CNVs to disease in BBS patients is much higher than previously expected, and demonstrated the necessity of consideration of CNV contribution in future (and retrospective) investigations of human genetic disease.

Finally, we used a combination of comparative genomics and in vivo complementation assays to identify second-site compensatory modification of pathogenic alleles. These pathogenic alleles, which are found compensated in other species (termed compensated pathogenic deviations [CPDs]), represent a significant fraction (from 3 – 10%) of human disease-associated alleles. In silico pathogenicity prediction algorithms, a valuable method of allele prioritization, often misrepresent these alleles as benign, leading to omission of possibly informative variants in studies of human genetic disease. We created a mathematical model that was able to predict CPDs and putative compensatory sites, and functionally showed in vivo that second-site mutation can mitigate the pathogenicity of disease alleles. Additionally, we made publically available an in silico module for the prediction of CPDs and modifier sites.

These studies have advanced the ability to interpret the pathogenicity of multiple types of human variation, as well as made available tools for others to do so as well.

Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables

In my thesis, “Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables,” I ask and answer the ‘Who? What? Where? When? Why?” of Creole Literature using the 19th century production of Aesopian fables as clues to resolve a set of linguistic, historical, literary, and geographical enigmas pertaining the ‘birth-place(s)’ of Creolophone Literatures in the Caribbean Sea, North and South America, as well as the Indian Ocean. Focusing on the fables in Martinique (1846), Reunion Island (1826), and Mauritius (1822), my thesis should read be as an attempt capture the links between these islands through the creation of a particular archive defined as a cartulary-chronicle, a diplomatic codex, or simply a map in which I chart and trace the flight of the founding documents relating to the lives of the individual authors, editors, and printers in order to illustrate the articulation of a formal and informal confederation that enabled the global and local institutional promotion of Creole Literature. While I integrate various genres and multi-polar networks between the authors of this 19th century canon comprised of sacred and secular texts such as proclamations, catechisms, and proverbs, the principle literary genre charted in my thesis are collections of fables inspired by French 17th century French Classical fabulist, Jean de la Fontaine. Often described as the ‘matrix’ of Creolophone Literature, these blues and fables constitute the base of the canon, and are usually described as either ‘translated,’ ‘adapted,’ and even ‘cross-dressed’ into Creole in all of the French Creolophone spaces. My documentation of their transnational sprouting offers proof of an opaque canonical formation of Creole popular literature. By constituting this archive, I emphasize the fact that despite 200 years of critical reception and major developments and discoveries on behalf of Creole language pedagogues, literary scholars, linguists, historians, librarians, archivist, and museum curators, up until now not only have none have curated this literature as a formal canon. I also offer new empirical evidence in order to try and solve the enigma of “How?” the fables materially circulated between the islands, and seek to come to terms with the anonymous nature of the texts, some of which were published under pseudonyms. I argue that part of the confusion on the part of scholars has been the result of being willfully taken by surprise or defrauded by the authors, or ‘bamboozled’ as I put it. The major paradigmatic shift in my thesis is that while I acknowledge La Fontaine as the base of this literary canon, I ultimately bypass him to trace the ancient literary genealogy of fables to the infamous Aesop the Phrygian, whose biography – the first of a slave in the history of the world – and subsequent use of fables reflects a ‘hidden transcript’ of ‘masked political critique’ between ‘master and slave classes’ in the 4th Century B.C.E. Greece.

This archive draws on, connects and critiques the methodologies of several disciplinary fields. I use post-colonial literary studies to map the literary genealogies Aesop; use a comparative historical approach to the abolitions of slavery in both the 19th century Caribbean and the Indian Ocean; and chart the early appearance of folk music in early colonial societies through Musicology and Performance Studies. Through the use of Sociolinguistics and theories of language revival, ecology, and change, I develop an approach of ‘reflexive Creolistics’ that I ultimately hope will offer new educational opportunities to Creole speakers. While it is my desire that this archive serves linguists, book collectors, and historians for further scientific inquiry into the innate international nature of Creole language, I also hope that this innovative material defense and illustration of Creole Literature will transform the consciousness of Creolophones (native and non-native) who too remain ‘bamboozled’ by the archive. My goal is to erase the ‘unthinkability’ of the existence of this ancient maritime creole literary canon from the collective cultural imaginary of readers around the globe.

The short and long of it: neural correlates of temporal-order memory for autobiographical events.

Previous functional neuroimaging studies of temporal-order memory have investigated memory for laboratory stimuli that are causally unrelated and poor in sensory detail. In contrast, the present functional magnetic resonance imaging (fMRI) study investigated temporal-order memory for autobiographical events that were causally interconnected and rich in sensory detail. Participants took photographs at many campus locations over a period of several hours, and the following day they were scanned while making temporal-order judgments to pairs of photographs from different locations. By manipulating the temporal lag between the two locations in each trial, we compared the neural correlates associated with reconstruction processes, which we hypothesized depended on recollection and contribute mainly to short lags, and distance processes, which we hypothesized to depend on familiarity and contribute mainly to longer lags. Consistent with our hypotheses, parametric fMRI analyses linked shorter lags to activations in regions previously associated with recollection (left prefrontal, parahippocampal, precuneus, and visual cortices), and longer lags with regions previously associated with familiarity (right prefrontal cortex). The hemispheric asymmetry in prefrontal cortex activity fits very well with evidence and theories regarding the contributions of the left versus right prefrontal cortex to memory (recollection vs. familiarity processes) and cognition (systematic vs. heuristic processes). In sum, using a novel photo-paradigm, this study provided the first evidence regarding the neural correlates of temporal-order for autobiographical events.

Sea Urchin Body Plan Development and Evolution: An Integrative Transcriptomic Approach

My dissertation work integrates comparative transcriptomics and functional analyses to investigate gene expression changes underlying two significant aspects of sea urchin evolution and development: the dramatic developmental changes associated with an ecologically significant shift in life history strategy and the development of the unusual radial body plan of adult sea urchins.

In Chapter 2, I investigate evolutionary changes in gene expression underlying the switch from feeding (planktotrophic) to nonfeeding (lecithotrophic) development in sea urchins. In order to identify these changes, I used Illumina RNA-seq to measure expression dynamics across 7 developmental stages in three sea urchin species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph Heliocidaris tuberculata, and an outgroup planktotroph Lytechinus variegatus. My analyses draw on a well-characterized developmental gene regulatory network (GRN) in sea urchins to understand how the ancestral planktotrophic developmental program was altered during the evolution of lecithotrophic development. My results suggest that changes in gene expression profiles occurred more frequently across the transcriptome during the evolution of lecithotrophy than during the persistence of planktotrophy. These changes were even more pronounced within the GRN than across the transcriptome as a whole, and occurred in each network territory (skeletogenic, endomesoderm and ectoderm). I found evidence for both conservation and divergence of regulatory interactions in the network, as well as significant changes in the expression of genes with known roles in larval skeletogenesis, which is dramatically altered in lecithotrophs. I further explored network dynamics between species using coexpression analyses, which allowed me to identify novel players likely involved in sea urchin neurogenesis and endoderm patterning.

In Chapter 3, I investigate developmental changes in gene expression underlying radial body plan development and metamorphosis in H. erythrogramma. Using Illumina RNA-seq, I measured gene expression profiles across larval, metamorphic, and post-metamorphic life cycle phases. My results present a high-resolution view of gene expression dynamics during the complex transition from pre- to post-metamorphic development and suggest that distinct sets of regulatory and effector proteins are used during different life history phases.

Collectively, my investigations provide an important foundation for future, empirical studies to investigate the functional role of gene expression change in the evolution of developmental differences between species and also for the generation of the unusual radial body plan of sea urchins.