Whole-genome sequencing allows researchers to study evolution through the lens of comparative genomics. Several landmark studies in yeast have showcased the utility of this approach for identifying functional elements, tracing the evolution of gene regulatory sites, and the revelation of an ancestral whole-genome duplication event. Such studies first require an accurate and comprehensive mapping of all orthologous loci across all species. In this chapter, we present a computational framework for systematic reconstruction of all gene orthology relations across multiple yeast species. We then discuss how to use the resulting genome- and species-wide catalogue of gene phylogenies to study the histories of gene duplications and losses from a functional genomics perspective. We show how these methods allowed us to uncover the functional constraints underlying gene duplications and losses within Ascomycota fungi, and to highlight the importance and limitations of these evolutionary processes. The analytical framework we present here is generalizable and scalable, and can be applied to an array of comparative genomics needs.
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