CALANGO: A phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species.

Living species vary significantly in phenotype and genomic content. Sophisticated statistical methods linking genes with phenotypes within a species have led to breakthroughs in complex genetic diseases and genetic breeding. Despite the abundance of genomic and phenotypic data available for thousands of species, finding genotype-phenotype associations across species is challenging due to the non-independence of species data resulting from common ancestry. To address this, we present CALANGO (comparative analysis with annotation-based genomic components), a phylogeny-aware comparative genomics tool to find homologous regions and biological roles associated with quantitative phenotypes across species. In two case studies, CALANGO identified both known and previously unidentified genotype-phenotype associations. The first study revealed unknown aspects of the ecological interaction between Escherichia coli, its integrated bacteriophages, and the pathogenicity phenotype. The second identified an association between maximum height in angiosperms and the expansion of a reproductive mechanism that prevents inbreeding and increases genetic diversity, with implications for conservation biology and agriculture.

Genome-Wide Survey of Genes Under Positive Selection in Avian Pathogenic Escherichia coli Strains.

The ability to obtain bacterial genomes from the same host has allowed for comparative studies that help in the understanding of the molecular evolution of specific pathotypes. Avian pathogenic Escherichia coli (APEC) is a group of extraintestinal strains responsible for causing colibacillosis in birds. APEC is also suggested to possess a role as a zoonotic agent. Despite its importance, APEC pathogenesis still has several cryptic pathogenic processes that need to be better understood. In this work, a genome-wide survey of eight APEC strains for genes with evidence of recombination revealed that ∼14% of the homologous groups evaluated present signs of recombination. Enrichment analyses revealed that nine Gene Ontology (GO) terms were significantly more represented in recombinant genes. Among these GO terms, several were noted to be ATP-related categories. The search for positive selection in these APEC genomes revealed 32 groups of homologous genes with evidence of positive selection. Among these groups, we found several related to cell metabolism, as well as several uncharacterized genes, beyond the well-known virulence factors ompC, lamB, waaW, waaL, and fliC. A GO term enrichment test showed a prevalence of terms related to bacterial cell contact with the external environment (e.g., viral entry into host cell, detection of virus, pore complex, bacterial-type flagellum filament C, and porin activity). Finally, the genes with evidence of positive selection were retrieved from genomes of non-APEC strains and tested as were done for APEC strains. The result revealed that none of the groups of genes presented evidence of positive selection, confirming that the analysis was effective in inferring positive selection for APEC and not for E. coli in general, which means that the study of the genes with evidence of positive selection identified in this study can contribute for the better understanding of APEC pathogenesis processes.