Telomere Roles in Fungal Genome Evolution

University Of Kentucky Research Foundation, Lexington KY

Investigators

Abstract

This project will examine the roles that telomeres, the DNA sequences that form the ends of chromosomes, play in chromosome evolution and in making new genes. The project will study chromosome ends in the filamentous fungus Magnaporthe oryzae - a devastating pathogen of rice and wheat plants. Of the more than 20 known genes that control fungus interactions with the host plants, at least 50% are found close to the telomeres. It has long been a puzzle as to how (and why) these genes find their ways to the chromosome ends. Recent work has shown that the M. oryzae chromosome ends undergo rearrangements at spectacularly high frequencies and this can lead to the capture and duplication of internal sequences at the chromosome ends. This, in turn, causes the formerly subtelomeric sequences to be relegated to the chromosome interior. This project will use DNA sequencing and related data analysis methods to test the hypothesis that telomere dynamics is a major driver of chromosome evolution. This project largely involves DNA sequencing and associated data analysis techniques (bioinformatics). Individuals with the relevant cross-training in biology and computer science are rare and collaborations between individuals from the two domains are challenged by differences in their training and skills. Recognizing a national need for individuals with dual domain expertise, most of the objectives for this project will be completed through research experiences for teams of biology and computer science undergraduates from the partner institutions of the Univ. of Kentucky, Northern Kentucky Univ., Eastern Kentucky Univ. and Western Kentucky Univ., with specific efforts being made to enhance participation for student populations traditionally underrepresented in STEM research. Despite intense interest in telomere biology and the importance of the associated chromosome regions (subtelomeres) in cellular biology, organismal adaptation and evolution, the organization of chromosome ends and their dynamics is poorly understood due to poor representation in genome assemblies. The central hypothesis driving this project is that the telomere regions are the main factories of fungal genome evolution, whereby recurrent bouts of telomere crisis provide the fuel for raw materials recruitment and telomere rescue pathways act to generate novel sequences. It has long been proposed that fungal genomes might evolve through such "Adaptive Telomere Failure" (ATF) but, until now, no examples had been identified. This project will greatly expand knowledge on fungal genome structure and reveal the full impact of ATF on genome organization and evolution. Additionally, it is suspected that enhanced rates of nucleotide substitution/indel polymorphism in the subtelomeric regions may further accelerate the neo-functionalization of terminally captured sequences. This project will test a number of predictions related to these hypotheses, while seeking to gain an improved understanding of subtelomere-internal genome sequence exchange, as it relates to fungal genome structure and host adaptation. Specific objectives include: 1. Generate end-to-end genome assemblies for the main host-specialized forms of M. oryzae and characterize the structural and genic diversity of the subterminal chromosome regions. 2. Assess the impact of telomere dynamics on M. oryzae genome evolution by identifying and characterizing internalized relics of former telomeres; 3. Examine genome reorganization following spontaneous or experimentally-induced telomere crisis events; and 4. Accomplish project objectives through "bite-sized" undergraduate research projects that foster collaboration between biologists and computer scientists.