Co-evolution of large inverted repeats and G-quadruplex DNA in fungal mitochondria may facilitate mitogenome stability: the case of Malassezia

Abstract

Mitogenomes are essential due to their contribution to cell respiration. Recently they have also been implicated in fungal pathogenicity mechanisms. Members of the basidiomycetous yeast genus Malassezia are an important fungal component of the human skin microbiome, linked to various skin diseases, bloodstream infections, and they are increasingly implicated in gut diseases and certain cancers. In this study, the comparative analysis of Malassezia mitogenomes contributed to phylogenetic tree construction for all species. The mitogenomes presented significant size and gene order diversity which correlates to their phylogeny. Most importantly, they showed the inclusion of large inverted repeats (LIRs) and G-quadruplex (G4) DNA elements, rendering Malassezia mitogenomes a valuable test case for elucidating the evolutionary mechanisms responsible for this genome diversity. Both LIRs and G4s coexist and convergently evolved to provide genome stability through recombination. This mechanism is common in chloroplasts but, hitherto, rarely found in mitogenomes.

Figure 1

Phylogeny and synteny of the mitogenome of 28 Malassezia strains representing all currently known species. The phylogenetic tree was produced using Bayesian Inference based on the concatenated amino acid matrix of the 15 mitochondrial PCGs. Numbers at the nodes of the tree indicate posterior probability (PP) values. The species Ustilago maydis strain 521 has been used as an outgroup. Shading of phylogenetic clusters is shown as green, yellow, purple, and blue for clades I, II, III and the basal species, respectively. Blue text indicates the taxa whose mt genome is presented for the first time in this study. Additionally, synteny is provided in all cases starting with rnl gene. The genes which are located on the complementary reverse strand are marked with red color. Amino acid symbols represent the corresponding tRNA gene (e.g., P for trnP). Genes referring to subunits of NADH complex, apocytochrome b, cytochrome c oxidase complex and ATP synthase complex are shown in green, orange, blue, light green respectively.

Figure 2

The main syntenic units of Malassezia mitogenomes. The first six units can be found in all Malassezia spp. (i.e., i–vi) while the last three in all except M. cuniculi (i.e., vii–ix). Arrows indicate gene transcription direction.

Figure 3

Schematic representation of Malassezia LIR evolution in relation to phylogeny. LIRs synteny is presented next to the respective phylogenetic clade. The intra-IR region can be seen in between black vertical lines. The genes located on the complementary reverse strand are indicated in red coloring and amino acid symbols represent the corresponding tRNA gene (e.g., H for trnH). The main evolutionary steps are shown as different colored symbols of the nodes and clades of the tree. Latin numbers in circles indicate the three different phylogenetic clades. The ancestral gene block of Ustilago maydis is provided.

Figure 4

The G-quadruplex distribution in Malassezia mitogenomes. Bar graphs of the predicted G4s with threshold 1.2 and window size 25 (left) or window size 30 (right). The G4s located in the trnP, LIRs, trnK, intergenic regions, introns and atp9 gene are shown with blue, orange, grey, yellow, light blue and green color, respectively.