Insight Into Human Brain Evolution Through Phylogenetic Analysis And Comparative Genomics

178 Pages·2015·4.57 MB·English

Wayne State University
Wayne State University Dissertations
1-1-2013
Insight Into Human Brain Evolution Through
Phylogenetic Analysis And Comparative Genomics
Amy Marie Boddy
Wayne State University,
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Boddy, Amy Marie, "Insight Into Human Brain Evolution Through Phylogenetic Analysis And Comparative Genomics" (2013).Wayne
State University Dissertations.Paper 641.
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INSIGHT INTO HUMAN BRAIN EVOLUTION THROUGH PHYLOGENETIC
ANALYSIS AND COMPARATIVE GENOMICS

by
AMY M BODDY
DISSERTATION
Submitted to the Graduate School
of Wayne State University,
Detroit, Michigan
in partial fulfillment of the requirements
for the degree of
DOCTOR OF PHILOSOPHY
2013
MAJOR: MOLECULAR BIOLOGY & GENETICS
Approved By:

_______________________________________
Advisor Date
© COPYRIGHT BY
AMY M BODDY
2013
All Rights Reserved
DEDICATION

This work is dedicated to my family. To my husband, Mike, without his love and support
this would not be possible. And to my daughter Reagan, your smile can carry me over
any obstacle.

ii
ACKNOWLEDGMENTS

First and foremost, I would like to thank my advisor, Derek Wildman, I am very
grateful for all his guidance throughout the years. His training has shown me how to
become an independent researcher and I have no doubt I would not be here today
without his support. I value his enthusiasm for science and his unique ability to think
outside of the box. He has taught me how to ask the right questions and has shown me
how to think creatively.
I would also like to thank my committee members, Dr. Kapatos, Dr. Krawetz, and
Dr. Sherwood. Their valuable suggestions, constructive criticism, and encouraging
discussions have helped me greatly. I would like to acknowledge the late Dr. Morris
Goodman. I am forever honored to have been a student of his. His dedication to
science, humble attitude, and words of inspiration will never be forgotten. I would like to
thank the CMMG office staff, especially Suzanne Shaw for her continuous assistance
throughout the years. A very special thank you to the late Mary Anne Housey, her
constant encouragement and belief in me will be remembered forever. I am greatly
indebted to Wildman lab members past and present. Their contribution, guidance and
friendship have made this experience unforgettable.
Last but not least, I would like to thank my family and friends. Their endless
support and encouragement have been a major motivating factor throughout my
graduate career.

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TABLE OF CONTENTS

Dedication ……………………………………………………………………………………… iii
Acknowledgments …………………………………………………………………………..... iv
List of Tables ………………………………………………………………………….............. v
List of Figures …………………………………………………………………………………. vi
Chapter 1: Introduction ……………………………………………………………………….. 1
Chapter 2: Comparative analysis of encephalization in mammals reveals relaxed
constraints on anthropoid primate and cetacean brain scaling (Published
JEB 2013) ……………………………………………………………………….. 25
Chapter 3: Evidence for positive selection and parallel brain evolution in the neocortical
transcriptome of a capuchin monkey ………………………………...……….. 58
Chapter 4: Conclusion ……………………………………………………………………… 93
Appendix A: Chapter 2 Supplemental Material …………………………………………..100
Appendix B: Chapter 3 Supplemental Material …………………………………………. 121
References …………………………………………………………………………............. 128
Abstract ………………………………………………………………………….................. 168
Autobiographical Statement ………………………………………………………………. 170

iv
LIST OF TABLES

TABLE 1: Summary of species and mean EQ ………………….....…………….….…… 39
TABLE 2: Summary of sequencing reads …………….…………....……………..……… 69
TABLE 3: Sequencing assembly statistics …………………..……..……………..……... 70
TABLE 4: Genes with adaptively evolving on capuchin and human lineages ……...... 77
TABLE 5: Enriched biological processes on the human lineage …………….…..……. 78
TABLE 6: Enriched biological processes on the capuchin monkey lineage …….….… 79
TABLE 7: Enriched biological processes on encephalized lineages ………….…….… 81
TABLE S1: Brain /body mass and EQ Dataset of 630 mammals ………….………… 100
TABLE S2: PGLS phylogenetic signal ……………………………………………….….. 115
TABLE S3: Parsimony REML summary ……………………………………………..….. 115
TABLE S4: Genes with accelerated rate of evolution on the human lineage ……….. 121
TABLE S5: Genes with accelerated rate of evolution on the capuchin lineage …….. 123
TABLE S6: Biological processes enriched in the human and capuchin accelerated
gene set …………………...………………………………………………..…. 125

v
LIST OF FIGURES

FIGURE 1: Brain expansion on the human lineage ….………………………………........ 6
FIGURE 2: Body and brain mass linear regression .....………………………………..... 38
FIGURE 3: Ancestral reconstruction of encephalization quotients in mammals ..……. 41
FIGURE 4: Boxplot of EQ in mammals ……………………………………………...……. 42
FIGURE 5: Boxplot of EQ in Primates and Cetartiodactyla …...…………………..……. 45
FIGURE 6: Homologous genes …………….……………..………………………...……. 66
FIGURE 7: Histogram of assembled contigs ……………..………………………...……. 70
FIGURE 8: Sequence and assembly pipeline …………………………………….……… 71
FIGURE 9: Summary of gene alignments ………………………….…………….....……. 72
FIGURE 10: Human and capuchins have a large relative brain size ………….....……. 73
FIGURE 11: Homo and Cebus demonstrate the largest increase in encephalization .. 74
FIGURE 12: Patterns of adaptive evolution among encephalized lineages …………... 74
FIGURE 13: Adaptive evolution summary results ……………………………………….. 76
FIGURE 14: Relationship between dN/dS and length of sequence ………….......……. 76
FIGURE S1: Colored representation of body/brain relationship in mammals ……….. 116
FIGURE S2: Body/brain regression for female mammals …………………….……..…116
FIGURE S3: Brain/body regressions taking phylogeny into consideration ………….. 117
FIGURE S4: Boxplot of PGLS derived EQ in mammals …………………………..…... 118
FIGURE S5: Boxplot of PGLS derived EQ in Primates ……………………….……….. 119
FIGURE S6: Boxplot of PGLS derived EQ in Cetartiodactyla ………………..……….. 120
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1

CHAPTER 1
Introduction

Encephalization, defined as an increase in brain size relative to body size, is a
major hallmark in primate evolution (Jerison 1973). As a species, humans are unique
among primates, especially in respect to their large brain size. Humans are the most
encephalized mammal, with the human brain six-fold larger than expected relative to
body mass (Jerison 1973, Martin 1981). Relevantly, there are distinct differences in
cognitive abilities in humans compared to other species. It is not unreasonable to
presume cognition and brain size may have coevolved (Lefebvre 2012). Although
evolving a large brain may seem advantageous in regards to intelligence, it comes at a
high cost, consuming approximately 20% of total energy in the body (Aiello and Wheeler
1995), and introduces susceptibility to human specific neurodegenerative diseases
(Sherwood, Subiaul et al. 2008). Insight into human brain evolution can help uncover
molecular mechanisms involved in such diseases and can shed light on how humans
evolved these enhanced cognitive abilities.
The aim of my research is to incorporate phylogenetic and comparative
techniques to identify some of the key components involved in the evolution of the
2
primate brain. I am interested in what makes the human brain unique, and the tradeoffs
our ancestors may have had to endure to acquire such a trait. In this regard, I have
implemented two approaches to study primate brain evolution, and these two
approaches are broken down into two chapters (Chapter 2 and 3). The first aim
explores brain size patterns in mammals using phylogenetic analyses. I collected
absolute brain and body mass from published literature from over 20 orders of
Mammalia, represented by 630 species, calculated relative brain size and reconstructed
the ancestral states. The goal of this study was to infer at which points during
mammalian evolution significant changes in brain size occurred. We determined there
was a significant change along the anthropoid primate and cetacean lineages, where
we discovered greater variance and relaxed constraints in these groups. These results
provide evidence for convergent/parallel evolution of brain expansion among specific
clades within Mammalia. We also confirmed the second most encephalized primate was
the capuchin monkey (Cebus sp.). These results set the foundation for the second aim.
As discussed in Chapter 3, I am interested in genetic contributions to primate brain
expansion. I implemented a comparative genomics approach and sequenced the
neocortical brain transcriptome of a capuchin monkey using next-generation sequencing
technologies. I tested for patterns of convergent brain evolution by identifying brain
expressed genes that are adaptively evolving on the human and capuchin monkey
lineages. As humans and capuchin monkeys are the two most encephalized primates,
we would expect genes involved in brain expansion would show similar patterns of
evolution on the two lineages. Because the brain is metabolically expensive, we
hypothesized genes involved in energy metabolism will have evidence for adaptive