GENETIC INFERENCES ON HUMAN EVOLUTIONARY HISTORY IN SOUTHERN ARABIA AND THE LEVANT By DEVEN N. VYAS A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2017 © 2017 Deven N. Vyas To my parents, sisters, and nephews and in memory of my grandmother, Ba. ACKNOWLEDGMENTS First, I would also like to thank my parents and sisters and the rest of my family for all their love and support. I want to thank my advisor and mentor, Dr. Connie J. Mulligan for all her advice, support, and guidance throughout my graduate career. I would also like to thank my other committee members, Dr. Steven A. Brandt, Dr. John Krigbaum, and Dr. David L. Reed for their input and guidance. I would also like to thank the many former and current postdocs, graduate students, and undergraduate students from the Mulligan lab including Dr. David A. Hughes, Dr. Laurel N. Pearson, Dr. Jacklyn Quinlan, Dr. Aida T. Miró-Herrans, Dr. Tamar E. Carter, Dr. Peter H. Rej, Christopher J. Clukay, Kia C. Fuller, Félicien M. Maisha, and Chu Hsiao for all their advice throughout the years as well as prior lab members Dr. Andrew Kitchen and Dr. Ryan L. Raaum who gave me much advice and guidance from afar. Finally, I would like to express thank the Yemeni people without whose participation none of this research would have been possible. 4 TABLE OF CONTENTS page ACKNOWLEDGMENTS .................................................................................................. 4 LIST OF TABLES ............................................................................................................ 7 LIST OF FIGURES .......................................................................................................... 8 LIST OF OBJECTS ....................................................................................................... 10 ABSTRACT ................................................................................................................... 11 CHAPTER 1 INTRODUCTION .................................................................................................... 13 2 BAYESIAN ANALYSES OF YEMENI MITOCHONDRIAL GENOMES SUGGEST MULTIPLE MIGRATION EVENTS WITH AFRICA AND WESTERN EURASIA ................................................................................................................ 29 Materials and Methods............................................................................................ 33 Ethics Statement .............................................................................................. 33 Sample Mitogenome Sequencing ..................................................................... 33 Bayesian Evolutionary Analysis ........................................................................ 35 Results .................................................................................................................... 38 Sequencing Results ......................................................................................... 38 Haplogroup Frequencies .................................................................................. 39 Analysis of Methodology................................................................................... 40 Bayesian Evolutionary Analysis of Yemeni Sequences .................................... 41 Haplogroup L0 ........................................................................................... 41 Haplogroup L3(xM,N) ................................................................................. 42 Haplogroup M1 .......................................................................................... 43 Haplogroup N1 ........................................................................................... 44 Discussion .............................................................................................................. 45 Testing Support for the Southern Dispersal Route ........................................... 49 Eurasian Origin of Haplogroup M1 ................................................................... 50 Conclusion ........................................................................................................ 51 3 TESTING SUPPORT FOR THE NORTHERN AND SOUTHERN DISPERSAL ROUTES OUT OF AFRICA: AN ANALYSIS OF LEVANTINE AND SOUTHERN ARABIAN POPULATIONS ...................................................................................... 53 Materials and Methods............................................................................................ 57 Ethics Statement .............................................................................................. 57 Sample Selection and Genotyping ................................................................... 57 Datasets Analyzed ........................................................................................... 59 5 Calculation of Near Eastern Ancestry Proportions ........................................... 60 Calculation of Outgroup f3 Statistics ................................................................. 61 Results .................................................................................................................... 62 Analysis of Near East Ancestry Proportions ..................................................... 62 Analysis of Outgroup f3 Statistics ..................................................................... 65 Discussion .............................................................................................................. 67 Inferences of Population Genetic Structure from Ancestry Proportions ............ 67 Relatedness of Populations along the NDR and SDR ...................................... 68 Relatedness of Levantine and Southern Arabian Populations to Non- Africans from Around the World .................................................................... 69 Relatedness of Levantine and Southern Arabian populations to Each Other ... 70 Conclusions on the Dispersal Out of Africa Based on Multiple Data Types ..... 71 Summary .......................................................................................................... 78 4 ANALYSES OF NEANDERTHAL INTROGRESSION SUGGEST THAT LEVANTINE AND SOUTHERN ARABIAN POPULATIONS HAVE A SHARED HISTORY OF INTROGRESSION ........................................................................... 90 Materials and Methods............................................................................................ 96 Datasets Analyzed ........................................................................................... 96 Calculation of f4 and D Statistics ...................................................................... 98 Identification of Neanderthal-Introgressed SNPs ............................................ 100 Results .................................................................................................................. 102 Neanderthal Introgression Estimates using f4 and D Statistics ....................... 102 Analysis of Neanderthal Allele Frequencies ................................................... 104 Discussion ............................................................................................................ 107 Comparing Levels of Neanderthal Introgression ............................................ 107 Comparing Frequencies of Neanderthal Alleles ............................................. 109 Inferences about the History of Introgression in the Levant and Southern Arabia .......................................................................................................... 112 Description of introgression models. ........................................................ 112 Assessment of introgression models ....................................................... 114 Summary ........................................................................................................ 118 5 CONCLUSION ...................................................................................................... 132 APPENDIX: FIGURES AND TABLES FOR CHAPTER 2 ........................................... 142 LIST OF REFERENCES ............................................................................................. 151 BIOGRAPHICAL SKETCH .......................................................................................... 166 6 LIST OF TABLES Table page 3-1 Cross Validation (CV) values for all ADMIXTURE replicate analyses ................ 88 3-2 Pairwise FST values for inferred ancestral components from ADMIXTURE (K=9) ................................................................................................................... 89 4-1 Values of f4 ratios estimating proportions of Neanderthal introgression in the Levant and southern Arabia and other regions of the world ............................. 126 4-2 D statistics comparing the level of Neanderthal introgression in the Levant and southern Arabia to other regions ............................................................... 127 4-3 D statistics comparing the level of Neanderthal introgression between individual Levantine and southern Arabian populations .................................... 128 4-4 The numbers of SNPs found in different types of functional regions ................ 130 4-5 The numbers of Neanderthal alleles present in the pooled populations ........... 131 A-1 Comparison of phylogenetic analyses that include additional non-M1/N1 sequences