Abstract

Budding yeasts inhabit a range of environments by exploiting various metabolic traits. The genetic bases for these traits are mostly unknown, preventing their addition or removal in a chassis organism for metabolic engineering. Insight into the evolution of orthologs, paralogs and xenologs in the yeast pan-genome can help bridge these genotypes; however, existing phylogenomic databases do not span diverse yeasts, and sometimes cannot distinguish between these homologs. To help understand the molecular evolution of these traits in yeasts, we created Analyzing Yeasts by Reconstructing Ancestry of Homologs (AYbRAH), an open-source database of predicted and manually curated ortholog groups for 33 diverse fungi and yeasts in Dikarya, spanning 600 million years of evolution. OrthoMCL and OrthoDB were used to cluster protein sequence into ortholog and homolog groups, respectively; MAFFT and PhyML reconstructed the phylogeny of all homolog groups. Ortholog assignments for enzymes and small metabolite transporters were compared to their phylogenetic reconstruction, and curated to resolve any discrepancies. Information on homolog and ortholog groups can be viewed in the AYbRAH web portal (https://lmse.github.io/aybrah/), including functional annotations, predictions for mitochondrial localization and transmembrane domains, literature references and phylogenetic reconstructions. Ortholog assignments in AYbRAH were compared to HOGENOM, KEGG Orthology, OMA, eggNOG and PANTHER. PANTHER and OMA had the most congruent ortholog groups with AYbRAH, while the other phylogenomic databases had greater amounts of under-clustering, over-clustering or no ortholog annotations for proteins. Future plans are discussed for AYbRAH, and recommendations are made for other research communities seeking to create curated ortholog databases.

Highlights

  • Yeasts are unicellular fungi that exploit diverse habitats on every continent, including the gut of wood boring beetles, insect frass, tree exudate, rotting wood, rotting cactus tissue, soil, brine solutions and fermenting juice [1]

  • Existing ortholog databases do not span diverse yeasts (Figure 1), and sometimes cannot distinguish between orthologs and paralogs (Tables S1 and S2). In addition to these databases, orthologs are identified on an ad hoc basis with OrthoMCL for comparative genomics studies [30, 31], or with the reciprocal best hit (RBH) method for genome-scale network reconstructions (GENREs) [32]; these ortholog assignments often lack transparency or traceability, and cannot be scrutinized or continuously improved by research communities. To solve these outlined problems, and improve our understanding of budding yeast physiology, we present Analyzing Yeasts by Reconstructing Ancestry of Homologs (AYbRAH; Figure 2)

  • We discuss the information available in the AYbRAH web portal, issues that arose from reviewing the accuracy of ortholog predictions, compare AYbRAH to established phylogenomic databases, discuss the benefits of opensource ortholog databases, future directions for AYbRAH, and offer recommendations to research communities looking to develop ortholog databases for other taxa

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Summary

Introduction

Yeasts are unicellular fungi that exploit diverse habitats on every continent, including the gut of wood boring beetles, insect frass, tree exudate, rotting wood, rotting cactus tissue, soil, brine solutions and fermenting juice [1]. Existing ortholog databases do not span diverse yeasts (Figure 1), and sometimes cannot distinguish between orthologs and paralogs (Tables S1 and S2) In addition to these databases, orthologs are identified on an ad hoc basis with OrthoMCL for comparative genomics studies [30, 31], or with the reciprocal best hit (RBH) method for genome-scale network reconstructions (GENREs) [32]; these ortholog assignments often lack transparency or traceability, and cannot be scrutinized or continuously improved by research communities. To solve these outlined problems, and improve our understanding of budding yeast physiology, we present Analyzing Yeasts by Reconstructing Ancestry of Homologs (AYbRAH; Figure 2). We discuss the information available in the AYbRAH web portal (https://lmse.github. io/aybrah/), issues that arose from reviewing the accuracy of ortholog predictions, compare AYbRAH to established phylogenomic databases, discuss the benefits of opensource ortholog databases, future directions for AYbRAH, and offer recommendations to research communities looking to develop ortholog databases for other taxa

Methods
Literature references
Findings
Conclusion

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