臺灣博碩士論文加值系統

木黴菌(Trichoderma spp.)為一群環境中常見的絲狀真菌，它們廣泛存在於土壤與其他多樣化環境中，且是容易培養的土壤真菌之一。多數木黴菌因能大量分泌酵素(如植物細胞壁水解酵素)與二級代謝化合物(如抗生素、植物荷爾蒙)，可以機會性共生、腐生或寄生等方式與植物、動物(如線蟲)或其他真菌發生交互作用，不僅對自然環境影響重大，也被廣泛應用於生產酵素、抗生素生產，或直接應用生物肥料、生物防治劑與殺蟲劑。木黴菌屬包括三個主要分支：Longibrachiatum、Trichoderma 與 Harzianum，本論文利用第三代核酸定序技術完整解序且註解此三個主要分支中的五個具高經濟價值的木黴菌物種的全基因體，包括QM6a、CBS999.97(MAT1-1)、CBS999.97(MAT1-2) 瑞氏木黴菌(T. reesei)、FT101棘孢木黴菌 (T. asperellum)和FT333綠木黴菌(T. virens)。CBS999.97能以無性與有性生殖方式繁衍，QM6a、FT101和FT33只以菌絲營養生長或產生無性孢子方式繼代。我們利用比較基因體學方法，發現生物防治用的FT101與FT333基因體經歷了大規模的基因流失與變異，尤以轉錄因子和減數分裂專一性基因最顯著。另一方面，這三種不同木黴菌均各自演化出獨特的分泌性效應性蛋白與酵素，用以適應不同宿主和環境。本論文第二個重點是研究芮氏木黴菌減數分裂與基因組防禦的分子機制，我們不僅建立了雜交減數分裂系統，也開發了全面性檢測減數分裂DNA重組與變異的基因體學實驗方法和新穎生物資訊學程式，這些研究成果足以讓瑞氏木黴菌成為研究絲狀真菌有性生殖、減數分裂、基因體演化與經濟應用的新興模式生物。

Trichoderma spp. are among the most useful microbes for humankind. They are present in nearly all soils and other diverse habitats. In soil, they frequently are the most prevalent culturable fungi. Trichoderma can interact with plants as opportunistic symbionts and with other fungi or animals via mycoparasitic interactions. The genus of Trichoderma contains three major sections or clades: Longibrachiatum (e.g., T. reesei), Trichoderma (e.g., T. asperellum) and Harzianum (e.g., T. virens). We have determined near-complete and highest-quality genome sequences of five Trichoderma strains, including T. reesei QM6a, CBS999.97(MAT1-1), CBS999.97(MAT1-2), T. asperellum FT101 and T. virens FT333. QM6a is the ancestor of almost all workhorse mutants used for the production of industrial enzymes and secondary metabolites, whereas asperellum FT101 and T. virens FT333 are two biocontrol or biofertilizer strains indigenous to Taiwan. CBS999.97(MAT1-1) and CBS999.97(MAT1-2) are both female and male fertile. In contrast, QM6a, FT101 and FT333 are female sterile or sexually incompetent. Our comparative genomic analyses reveal that FT101 and FT333, like QM6a, have undergone significant gene mutation and loss, most profoundly in genes encoding transcriptional factor and meiosis-specific proteins, explaining why they can only propagate asexually. Interestingly, these three species each has evolved a special set of secreted enzymes or effector proteins for host and environmental niche adaptation. In this study, we have established genetic and genomic protocols to study T. reesei sexual development and also invented innovative software tools for genome-wide mapping of all genetic variations before and after sexual crossing. Trichoderma spp. have long been used for studying the molecular mechanisms of industrial enzyme production, mycoparasitism and plant-fungal interactions. In conclusion, we have demonstrated explicitly that T. reesei can be used a new model organism for studying filamentous fungal sexual development, meiosis and genome evolution.

中文摘要............................................................................................................ IV
ABSTRACT........................................................................................................X
CHAPTER 0.............................................................................................................................1
GENERAL INTRODUCTION...............................................................................................1
What is Trichoderma?..................................................................................................................................1
Sexual reproduction in Trichoderma ..........................................................................................................2
Pan-genomics in the Trichoderma genome era ..........................................................................................3
OUTLINE............................................................................................................................................................5
CHAPTER 1.............................................................................................................................8
LONG-READ SEQUENCING, GENOME-WIDE ANNOTATION AND COMPARATIVE GENOMIC ANALYSES OF FIVE ECONOMICALLY IMPORTANT TRICHODERMA SPP. STRAINS .................................................................8
INTRODUCTION ...........................................................................................................................................8
MATERIALS AND METHODS ....................................................................................................................9
RESULTS .......................................................................................................................................................11
Long-read sequencing and using the third-generation sequencing (TGS) technology ...........................11
All five Trichoderma genomes have high number of interspersed AT-rich blocks .................................13
Repetitive features ......................................................................................................................................14
The mitochondrial genomes (mitogenomes) .............................................................................................15
Genome-wide gene prediction....................................................................................................................16
Chromosome synteny and rearrangements ...............................................................................................19
Asexual cell-to-cell communication and hyphae fusion...........................................................................20
Sexual mating and fruit body formation ...................................................................................................20
RIP, meiotic recombination and chromosome synapsis ...........................................................................21
Trichoderma-plant interactions .................................................................................................................24
Biosynthesis of natural products ...............................................................................................................24
Comparative analyses of carbohydrate-active enzymes (CAZymes), secreted proteins and transcriptional factors................................................................................................................................26
Chromosomal location of small secreted protein genes............................................................................26
DISCUSSION.................................................................................................................................................27
CHAPTER 2...........................................................................................................................30
DISCOVERY OF REPEAT-INDUCED POINT (RIP) MUTATIONS IN THE INDUSTRIAL WORKHORSE FUNGUS TRICHODERMA REESEI.............................30
INTRODUCTION .........................................................................................................................................30
MATERIALS AND METHODS ..................................................................................................................32
RESULTS .......................................................................................................................................................32
The bioinformatic evidence for the operation of RIP in T. reesei ............................................................33
The molecular genetic evidence for the operation of RIP in T. reesei .....................................................33
RIP operates differently in Trichoderma reesei and Neurospora crassa .................................................34
DISCUSSION.................................................................................................................................................35
CHAPTER 3...........................................................................................................................37
TRICHODERMA REESEI RAD51 TOLERATES MISMATCHES IN HYBRID MEIOSIS WITH DIVERSE GENOME SEQUENCES.....................................................37
INTRODUCTION .........................................................................................................................................37
MATERIALS AND METHODS ..................................................................................................................39
RESULTS .......................................................................................................................................................42
II
QM6a and CBS999.97 exhibit high levels of sequence heterogeneity .....................................................42
Genome-wide detection of meiotic recombination products with single-nucleotide precision................43
SNPs in the GC tracts of interhomolog recombination products .............................................................46
T. reesei rad51 is indispensable for DNA damage repair during normal vegetative growth and meiosis ....................................................................................................................................................................47
Production of TrRad51 for biochemical and single molecular biophysical analyses..............................48
Identification of amino acid residues in TrRad51 responsible for mismatch tolerance during meiotic recombination.............................................................................................................................................49
DISCUSSION.................................................................................................................................................51
CHAPTER 4...........................................................................................................................55
THIRD-GENERATION SEQUENCING-BASED MAPPING AND VISUALIZATION OF SINGLE NUCLEOTIDE POLYMORPHISMS, MEIOTIC RECOMBINATION PRODUCTS AND REPEAT-INDUCED POINT MUTATIONS .....................................55
INTRODUCTION .........................................................................................................................................55
MATERIALS AND METHODS ..................................................................................................................59
RESULTS .......................................................................................................................................................61
TSETA is a BLASTN-guided and sectional MAFFT program ................................................................61
TSETA enables comprehensive sequence alignment and comparative analyses.....................................63
Alignment of centromeres and large rDNA loci is problematic ...............................................................64
Accuracy assessment of TSETA ................................................................................................................67
TSETA is a versatile tool for genome-wide variant calling ......................................................................68
Genome-wide identification of interhomolog recombination products and RIP mutations....................68
TSETA is a powerful tool for global and local visualization of sequence variants .................................70
DISCUSSION.................................................................................................................................................72
CHAPTER 5...........................................................................................................................76
TWO DIFFERENT PATHWAYS FOR INITIATION OF TRICHODERMA REESEI RAD51-ONLY MEIOTIC RECOMBINATION................................................................76
INTRODUCTION .........................................................................................................................................76
MATERIALS AND METHODS ..................................................................................................................77
RESULTS .......................................................................................................................................................79
T. reesei spo11, unlike rad51 or sae2, is dispensable for normal meiosis................................................79
T. reesei exhibits spo11-independent interhomolog recombination.........................................................80
T. reesei spo11 is dispensable for chromosome synapsis during meiosis.................................................82
Comparative analysis of COs and NCOs in the presence or absence of spo11........................................83
Interhomolog recombination products tend to be located at 3′-regions of protein-encoding genes in the spo11Δ mutant line.....................................................................................................................................84
Top2 might be responsible for Spo11-independent DSBs during T. reesei meiosis.................................85
DISCUSSION.................................................................................................................................................86
REFERENCES..................................................................................................89
TABLES...........................................................................................................102
FIGURES.........................................................................................................230

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