## 3 Gene Discovery and Gene Expression Analysis in the Pre-NGS Era  
In the pre-genomic era, several molecular approaches have been developed to screen endophytic fungi for potential producers of valuable secondary metabolites. Screening for molecular markers was (and still is) a popular method which enables detection of key biosynthetic genes in the endophyte genomes by a polymerase chain reaction (PCR) amplification. This technique is based on the design of degenerate PCR primers from sequences of known biosynthetic genes of plants to detect the presence of a certain gene in fungal genomes or environmental DNA, and to obtain its nucleotide sequence. This method was successfully used for identification of a _ts_ (encoding taxadiene synthase) and phenylpropanoyll transferase gene in _T. andreanae_[49], _ts_ and _bapt_ (encoding C-13 phenylpropanoyll side chain-CoA acyltransferase) in _Guignardia mansiferae_, _Fusarium proliferatum_, and _Colletotrichum gloosoporoides_ isolated from _Taxus x media_[50], _dbat_ (encoding 10-deacetylbaccatin III-10-O-acetyl transferase) in endophytic fungi isolated from _Salacia oblonga_[51], and _bapt_ in endophytic fungi isolated from _Taxus baccata_[52]. The presence of genes encoding for hyoscyamine 66-hydroxylase, putrescine N-methyltransferasearse and tropinone reductase 1 was reported by the PCR-based molecular marker screening approach in endophytic fungi isolated from _Datura metel_ producing tropane alkaloids [53]. In the past decade, a microarray-based technique allowed for transcriptome profiling in the high-throughput manner, thus it became an important step towards global transcriptomic analysis. A microarray-based technique was used to perform comparative transcript profiling in the grass fungal endophytes _Neotyphodium coenophilatum_, _Neotyphodium loli_, and _Epichloe festucae_[54], which allowed to investigate genome-specific gene expression, novel endophyte genes, and general plant-endophyte interactions through revealing factors supporting the establishment and maintenance of the mutualistic association. The microarray studies performed in filamentous fungi, reviewed by [PERSON] and [PERSON] [55], have helped revealing genes which play a role in the biosynthesis of both useful and detrimental secondary metabolites. There are no reports, however, on microarray studies performed in endophytic fungi, which would be employed for the discovery and analysis of structural genes involved in fungal biosynthesis of plant bioactive metabolites. Global Genome and Transcriptome Analysis for the Discovery of Plant-Like Secondary Metabolites Biosynthetic Genes in Endophytic Fungi  
Despite the astonishing number of species of endophytic fungi which are thought to exist [56; 57; 58; 59], we do not know a lot about the genomics and transcriptomics of this diverse kingdom. Databases containing genomes and transcriptomes of fungi are still poor in resources, even those dedicated to fungal research such as ENSEMBL Fungi (1014 complete genomes) [60], Mycocosm, the branch of Joint Genome Institute (JGI) [61], holding the \"1000 fungal genomes\" project and e-Fungi, run by the University of Exeter (UK) [62], with only 34 complete Fungal Genomes. Up to date, JGI offers 6 studies of gene expression profiling and only 228 records of endophytic fungi genomes. Richer resources are found in the GenBank and the initiative named International Nucleotide Sequence Database Collaboration (INSDC)--joint genomic resource database of the National Center of Biotechnological Information (NCBI), the Bioinformatics Institute (EBI), and the DNA Database of Japan (DDBJ). The Sequence Read Archive (SRA) is the NCBI database that stores sequence data obtained from next generation sequence technology. Thorough SRA database search revealed 2279 records for endophytic fungi, without taking into account data from uncultured fungi and metagenomics projects [63]. Out of these, 2230 records reported endophytic fungi genome sequencing and 49 deposited endophytic fungi transcriptomes.