THE EFFECTS OF ANEUPLOIDY ON GENE EXPRESSION IN A DOSAGE SERIES OF MAIZE CHROMOSOME ARM 1L A Dissertation Presented to The Faculty of the Graduate School At the University of Missouri In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy By Adam Johnson Dr. James Birchler, Dissertation Supervisor May, 2017 The undersigned, appointed by the dean of the Graduate School, have examined the Dissertation entitled THE EFFECTS OF ANEUPLOIDY ON GENE EXPRESSION IN A DOSAGE SERIES OF MAIZE CHROMOSOME ARM 1L Presented by Adam Johnson A candidate for the degree of Doctorate of Philosophy And hereby certify that, in their opinion, it is worthy of acceptance. ________________________________________________________ Dr. James Birchler ________________________________________________________ Dr. Jianlin Cheng ________________________________________________________ Dr. Kathleen Newton ________________________________________________________ Dr. J. Chris Pires ACKNOWLEDGMENTS To complete the work described in this dissertation, I relied on the help, guidance, and collaboration of many people. Here is a partial list of the colleagues, friends, and family who contributed to making this possible: Dr. James Birchler, for providing patience and sound reasoning to a guy who really needed it. All past and present members of the Birchler lab in every capacity, including Patrice Albert, Weihong Chen, Jon Cody, Ryan Donohue, Dr. Ryan Douglas, Dr. Robert Gaeta, Dr. Zhi Gao, Nat Graham, Spencer Lambdin, Morgan McCaw, Dr. Abhijit Sanyal, Dr. Xiaowen Shi, Dr. Lin Sun, Nathan Swyers, Dr. Weiwu Xie, Dr. Hua Yang, and Dr. Changzeng Zhao. Dr. Jianlin Cheng and his lab, including Jie Hou, Md Soliman Islam, and Dr. Jilong Li. Dr. Birchler, Dr. Cheng, Dr. Kathleen Newton, and Dr. Chris Pires for serving as my committee. Debbie Allen and the Life Sciences Fellowship, Vicki Bryan and the Interdisciplinary Plant Group, and Nila Emerich and the Division of Biological Sciences, for the support – financial, administrative, community, you name it. Dr. Birchler, Dr. David Braun, and Dr. Amanda Durbak for providing me the opportunity to teach under their guidance. My parents, John and Sally, and my brother and sister, Ryan and Rebecca. My wife and best friend, Linh Ngo, who knows why I saved this part for last. ii Table of Contents Acknowledgments............................................................................................................... ii List of Illustrations ............................................................................................................. iv Chapter 1 – Introduction ..................................................................................................... 1 Aneuploidy and gene dosage – history of the concept, occurrence in nature, and application to medicine ................................................................................................... 1 Gene expression studies – with methods including cytogenetics and discussion of results .............................................................................................................................. 6 The gene balance hypothesis – proposed mechanisms of aneuploid effects and interpretation of gene expression studies ...................................................................... 13 Chapter 2 – Modulation of gene expression in aneuploids involving the long arm of chromosome 1 of maize .................................................................................................... 17 Introduction ................................................................................................................... 17 Methods......................................................................................................................... 17 Results ........................................................................................................................... 21 Discussion ..................................................................................................................... 23 Chapter 3 – Functional analysis of gene dosage effects in a series of aneuploids for maize chromosome arm 1L ......................................................................................................... 55 Introduction and methods ............................................................................................. 55 Results and discussion .................................................................................................. 56 Chapter 4 – The Effects of Genomic Imbalance on Organisms of Different Kingdoms .. 65 Introduction ................................................................................................................... 65 Methods......................................................................................................................... 66 Results and discussion .................................................................................................. 67 Conclusion ........................................................................................................................ 87 Bibliography ..................................................................................................................... 88 Supplemental Figures........................................................................................................ 91 Vita .................................................................................................................................. 103 iii List of Illustrations Figures Figure 1 – Kinetics of a multi-subunit complex ............................................................... 16 Figure 2 – FISH image of trisomic chromosome spread .................................................. 20 Figure 3a – Ratio distribution plot for cis genes, haploid/diploid ................................... 27 Figure 3b – Ratio distribution plot for cis genes, trisomic/diploid ................................... 29 Figure 3c – Ratio distribution plot for cis genes, tetrasomic/diploid ................................ 30 Figure 3d – Ratio distribution plot for cis genes, disomic/haploid ................................... 31 Figure 3e – Ratio distribution plot for cis genes, monosomic/diploid, second dosage series ................................................................................................................................. 32 Figure 3f – Ratio distribution plot for cis genes, trisomic/diploid, second dosage series 33 Figure 4a – Ratio distribution plot for trans genes, haploid/diploid ................................. 34 Figure 4b – Ratio distribution plot for trans genes, trisomic/diploid ................................ 36 Figure 4c – Ratio distribution plot for trans genes, tetrasomic/diploid ............................ 37 Figure 4d – Ratio distribution plot for trans genes, disomic/haploid ............................... 38 Figure 4e – Ratio distribution plot for trans genes, monosomic/diploid, second dosage series ................................................................................................................................. 39 Figure 4f – Ratio distribution plot for trans genes, trisomic/diploid, second dosage series ........................................................................................................................................... 40 Figure 5a – Volcano plot for cis genes, haploid/diploid ................................................... 41 Figure 5b – Volcano plot for cis genes, trisomic/diploid.................................................. 42 Figure 5c – Volcano plot for cis genes, tetrasomic/diploid .............................................. 43 Figure 5d – Volcano plot for cis genes, disomic/haploid ................................................. 44 Figure 5e – Volcano plot for cis genes, monosomic/diploid, second dosage series ......... 45 Figure 5f – Volcano plot for cis genes, trisomic/diploid, second dosage series ............... 46 Figure 6a – Volcano plot for trans genes, haploid/diploid ................................................ 47 Figure 6b – Volcano plot for trans genes, trisomic/diploid .............................................. 48 Figure 6c – Volcano plot for trans genes, tetrasomic/diploid ........................................... 49 Figure 6d – Volcano plot for trans genes, disomic/haploid .............................................. 50 Figure 6e – Volcano plot for trans genes, monosomic/diploid, second dosage series ...... 51 Figure 6f – Volcano plot for trans genes, trisomic/diploid, second dosage series ............ 52 Figure 7a – Ratio distribution plots for transcription factor genes ................................... 59 Figure 7b – Ratio distribution plots for photosynthesis genes .......................................... 60 Figure 7c – Ratio distribution plots for G protein-related genes ...................................... 61 Figure 7d – Ratio distribution plots for ribosome component genes ................................ 62 Figure 7e – Ratio distribution plots for proteasome complex genes ................................ 63 Figure 8a – Ratio distribution plots for trisomy 1/diploid ................................................ 69 Figure 8b – Ratio distribution plots for trisomy 13/diploid .............................................. 70 Figure 8c – Ratio distribution plots for trisomy 16/diploid .............................................. 71 Figure 8d – Ratio distribution plots for