Trichosporonaceae incorporates six genera of physiologically and ecologically diverse fungi including both human pathogenic taxa as well as yeasts of biotechnological interest, especially those oleagenic taxa that accumulate large amounts of single cell oils (Scos). Here, we have undertaken comparative genomic analysis of thirty-three members of the family with a view to gain insight into the molecular determinants underlying their lifestyles and niche specializations. phylogenomic analysis revealed potential misidentification of three strains which could impact subsequent analyses. Evaluation of the predicted proteins coding sequences showed that the free-living members of the family harbour greater numbers of carbohydrate active enzymes (cAZYmes), metallo-and serine peptidases compared to their host-associated counterparts. phylogenies of selected lipid biosynthetic enzymes encoded in the genomes of the studied strains revealed disparate evolutionary histories for some proteins inconsistent with the core genome phylogeny. However, the documented oleagenic members distinctly cluster based on the constitution of the upstream regulatory regions of genes encoding acetyl-coA carboxylase (Acc), Atp-citrate synthase (AcS) and isocitrate dehydrogenase [nADp] (icDH), which are among the major proteins in the lipid biosynthetic pathway of these yeasts, suggesting a possible pattern in the regulation of these genes. The basidiomycetous fungal family Trichosporonaceae belongs to the order Trichosporonales, the class Tremellomycetes, and subphylum Agaricomycotina and incorporates morphologically and physiologically diverse, aromatic compound-assimilating yeasts 1. Recently the taxonomy of this family was revised to include six genera, namely Apiotrichum, Cutaneotrichosporon, Effuseotrichosporon, Haglerozyma, Trichosporon (type genus) and Vanrija. This revision was based on phylogenetic analysis of seven markers, namely LSU (D1/D2 domains) and SSU rRNA, the Internal Transcribed Spacer (ITS) and the protein coding genes RPB1, RPB2, TEF1 and CYTB and a combination of morphological, biochemical and physiological characteristics 1,2. Members of the Trichosporonaceae show a global distribution and have been recovered from a wide range of environments. Cutaneotrichosporon spp. are most frequently associated with a human host, and may represent opportunistic human pathogens. Trichosporon spp. form part of the natural microflora on human and animal skin and result in a non-serious mycosis of hair termed white piedra 3. However, they have also been implicated in trichosporonosis, a collection of opportunistic infections caused by a number of species, including Trichosporon asahii, T. asteroides and T. ovoides 4. By contrast Apiotrichum and Vanrija spp. are generally free-living and have been isolated from water bodies, food sources and rotten wood (Table 1). While the Trichosporonaceae include several opportunistic human pathogens, there has also been increased interest in these taxa for a broad range of biotechnological applications...