Genome architecture, rearrangement and evolution in the ciliate Oxytricha trifallax

Abstract

Genome rearrangements contribute to genome instability that is commonly associated with human diseases, especially cancer. Ciliates are best known for their programmed DNA rearrangements in a single cell that completely rewire a germline into a somatic nucleus during development. This elaborate, RNA-mediated pathway eliminates noncoding DNA sequences that interrupt gene loci and reorganizes the remaining fragments by inversions and permutations to produce functional genes. Comparative analysis of ciliate genomes, including the somatic, germline and mitochondrial genomes, will thus provide significant insights into the complexity of the genome architecture, the mechanisms of the genome rearrangement process, as well as the unique features of ciliate genome evolution. My PhD thesis is themed upon genome architecture, rearrangement and evolution in ciliates, with Oxytricha trifallax as a model.

Chapter 1 provides a general introduction to genome evolution, genome rearrangement and ciliate biology.

Chapter 2 describes the highly complex Oxytricha germline genome. We sequenced and assembled the Oxytricha germline genome and compare it to the somatic genome to present a global view of its massive scale of genome rearrangements. The remarkably encrypted genome architecture contains >225,000 gene segments, many of which are scrambled and interwoven with each other. This genome assembly provides the first draft of a scrambled genome and a powerful model for studies of genome rearrangement.

Chapter 3 reports alternative processing of gene segments as a novel mechanism to create new genes in ciliates. Comparative genome data from multiple ciliate species are used to investigate the origin of alternative DNA processing and the de novo genes created by this process.

Chapter 4 is a synthesis of phylogenomic analysis of the TBE transposons in the Oxytricha germline genome. I analyze the genomic distribution and sequence features of TBEs and report the genome-wide purifying selection on all three TBE-encoded genes. I also study TBE evolution by examining the presence of TBE homologs in other ciliate genomes.

Chapter 5 describes my work on comparative analysis of six ciliate mitochondrial genomes, shedding light on the unique genomic features as well as mitochondrial genome evolution.