Project description:Understanding how genomes encode complex cellular and organismal behaviors has become the outstanding challenge of modern genetics. Unlike classical screening methods, analysis of genetic variation that occurs naturally in wild populations can enable rapid, genome-scale mapping of genotype to phenotype with a medium-throughput experimental design. Here we describe the results of the first genome-wide association study (GWAS) used to identify novel loci underlying trait variation in a microbial eukaryote, harnessing wild isolates of the filamentous fungus Neurospora crassa. We genotyped each of a population of wild Louisiana strains at 1 million genetic loci genome-wide, and we used these genotypes to map genetic determinants of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion, and we subjected these trait measurements to GWAS. This analysis identified one gene, NCU04379 (cse-1, encoding a homolog of a neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly impaired germling communication and fusion, and two genes encoding predicted interaction partners of CSE1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more previously unknown molecular players, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. Our results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species.

Project description:Understanding how genomes encode complex cellular and organismal behaviors is an outstanding challenge of modern genetics. Unlike classical screening methods, analysis of the genetic variation that occurs naturally in wild populations can enable rapid, genome-scale trait mapping with a medium-throughput experimental design. Here we describe the results of the first genome-wide association analysis (GWAS) of a microbial eukaryote, using wild isolates of the filamentous fungus Neurospora crassa. We transcriptionally profiled each of 112 individuals collected in Louisiana and used RNA-seq data to genotype each strain at thousands of genetic loci genome-wide. We used these genotypes in a mapping analysis of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion. GWAS identified one gene, NCU04379 (cse-1, encoding a homolog of neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly lowered germling communication and fusion, and two genes encoding predicted binding partners of CSE-1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more novel determinants of germling communication, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. These results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species. 112 mycelial mRNA profiles of 16 hour wild type (WT) Neurospora crassa strains were generated by deep sequencing, using Illumina GAIIx.

Project description:Understanding how genomes encode complex cellular and organismal behaviors is an outstanding challenge of modern genetics. Unlike classical screening methods, analysis of the genetic variation that occurs naturally in wild populations can enable rapid, genome-scale trait mapping with a medium-throughput experimental design. Here we describe the results of the first genome-wide association analysis (GWAS) of a microbial eukaryote, using wild isolates of the filamentous fungus Neurospora crassa. We transcriptionally profiled each of 112 individuals collected in Louisiana and used RNA-seq data to genotype each strain at thousands of genetic loci genome-wide. We used these genotypes in a mapping analysis of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion. GWAS identified one gene, NCU04379 (cse-1, encoding a homolog of neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly lowered germling communication and fusion, and two genes encoding predicted binding partners of CSE-1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more novel determinants of germling communication, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. These results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species.

Dataset Information

Genome-wide association identifies novel ROP risk loci in a multi-ethnic cohort.

Publications

Genome-wide association identifies novel ROP risk loci in a multi-ethnic cohort.

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