Participant Support:Telomere Roles in Fungal Genome Evolution and Adaptation

Grants and Contracts Details

Description

Telomeres are the DNA sequences that form the ends of eukaryotic chromosomes. They counter the loss of terminal DNA during replication, prevent chromosome end fusions and guard against exonucleolytic attack. The adjacent subtelomere regions are usually highly polymorphic and, in microbes, they tend to harbor families of genes involved in niche adaptation. Good examples are the variable surface protein genes of Plasmodium (malaria) and Trypanosoma (sleeping sickness). It is believed that the dynamic subtelomere environment promotes variation in these genes, which in turn allows the pathogens to escape host recognition. An analogous situation exists in the filamentous fungus Magnaporthe oryzae - a model fungus and devastating pathogen of rice, wheat, forage crops and turf. Of the more than 20 known genes that control host interactions, at least 50% map extremely close to the telomeres - often less than 10 kb away. It has long been a puzzle as to how (and why) these genes find their ways to the chromosome ends. In some M. oryzae strains, the chromosome ends undergo rearrangements at spectacularly high frequencies. By characterizing many such alterations, we discovered that telomere integrity is frequently compromised and leads to the capture and duplication of internal sequences at the chromosome ends. Subsequent rounds of telomere crisis can then cause the newly captured sequences to be recruited back to the genome interior. Importantly, we have been able to identify large numbers of formerly-telomeric sequences ("telomere relics") at internal genomic locations in all strains of M. oryzae and in many other fungi, indicating that this middle-to-end-to-middle dynamic is widespread - and likely ubiquitous. Based on these observations, we hypothesize that the subtelomere regions are the main factories of fungal genome evolution, with recurrent bouts of telomere crisis providing the fuel for raw materials recruitment and telomere rescue pathways acting to generate novel sequences. Furthermore, we suspect that enhanced rates of nucleotide substitution/indel polymorphism in the subtelomeric regions (a generally accepted, but formally untested, idea) may further accelerate the neo-functionalization of captured sequences. This proposal focuses on testing a number of predictions related to this hypothesis, while seeking to gain an improved understanding of subtelomere'internal genome sequence exchange, as it relates to fungal genome structure and speciation. Specific objectives include: i) test if segmental duplications are more frequently associated with chromosome ends and telomere relics; ii) test if genes evolve more rapidly when in subtelomeric locations; iii) identify new genes generated though telomere rescue pathways; iv) examine the "genomic migration" patterns for products of the subtelomeric "factories," v) develop a web-accessible fungal telomeres database to house data generated in the project. Intellectual merit: Despite intense interest in telomere biology and the importance of these chromosome regions in organismal adaptation and evolution, chromosome end organization and dynamics is poorly understood due to poor (non-existent - in many cases) telomere representation in genome assemblies. Using tools developed in the Farman lab, this project will mine telomeric reads from raw sequence archives and link them to existing genomic scaffolds. In providing frames of reference for the chromosome ends, this will unlock a wealth of untapped genomic sequence information and allow exploration of how the chromosome ends have contributed to fungal genome evolution. Broader impacts: This project largely involves bioinformatics. Experience tells us that individuals with appropriate cross-training in biology and computer science (CS) are rare commodities and that collaborations between individuals from the two domains are challenged by "language" differences. Recognizing a national need for individuals with dual domain expertise, we plan to complete the proposed objectives entirely through research experiences for teams of biology and CS undergraduates. To accomplish this, we will leverage an ongoing bioinformatics training program, a state-wide bioinformatics network, and a national undergraduate research program, to provide next generation sequencing and bioinformatics training/research experiences to undergraduates from the partner institutions of the University of Kentucky, Northern Kentucky University, Eastern Kentucky University and Western Kentucky University, with specific efforts being made to enhance participation for student populations traditionally underserved in STEM research.
StatusActive
Effective start/end date7/15/176/30/23

Funding

  • National Science Foundation

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