Lichen-forming fungi are known to produce a large number of secondary metabolites. Some metabolites are deposited in the cortical layer of the lichen thallus where they exert important ecological functions, such as UV filtering. The fact that closely related lineages of lichen-forming fungi can differ in cortical chemistry suggests that natural product biosynthesis in lichens can evolve independent from phylogenetic constraints. Usnic acid is one of the major cortical pigments in lichens. Here we used a comparative genomic approach on 46 lichen-forming fungal species of the Lecanoromycetes to elucidate the biosynthetic gene content and evolution of the gene cluster putatively responsible for the biosynthesis of usnic acid. Whole-genome sequences were gathered from taxa belonging to different orders and families of Lecanoromycetes, where Parmeliaceae is the most well-represented taxon, and analyzed with a variety of genomic tools. The highest number of biosynthetic gene clusters was found in Evernia prunastri, Pannoparmelia angustata, and Parmotrema austrosinense, respectively, and lowest in Canoparmelia nairobiensis, Bulbothrix sensibilis, and Hypotrachyna scytodes. We found that all studied species producing usnic acid contain the putative usnic acid biosynthetic gene cluster, whereas the cluster was absent in all genomes of species lacking usnic acid. The absence of the gene cluster was supported by an additional unsuccessful search for ß-ketoacylsynthase, the most conserved domain of the gene cluster, in the genomes of species lacking usnic acid. The domain architecture of this PKS cluster—homologous to the already known usnic acid PKS cluster (MPAS) and CYT450 (MPAO)—varies within the studied species, whereas the gene arrangement is highly similar in closely related taxa. We hypothesize that the ancestor of these lichen-forming fungi contained the putative usnic acid producing PKS cluster and that the gene cluster was lost repeatedly during the evolution of these groups. Our study provides insight into the genomic adaptations to the evolutionary success of these lichen-forming fungal species and sets a baseline for further exploration of biosynthetic gene content and its evolutionary significance.

Phylogenomic datasets continue to enhance our understanding of evolutionary relationships in many lineages of organisms. However, genome-scale data have not been widely implemented in reconstructing relationships in lichenized fungi. Here we generate a data set comprised of 2556 single-copy protein-coding genes to reconstruct previously unresolved relationships in the most diverse family of lichen-forming fungi, Parmeliaceae. Our sampling included 51 taxa, mainly from the subfamily Parmelioideae, and represented six of the seven previously identified major clades within the family. Our results provided strong support for the monophyly of each of these major clades and most backbone relationships in the topology were recovered with high nodal support based on concatenated dataset and species tree analyses. The alectorioid clade was strongly supported as sister-group to all remaining clades, which were divided into two major sister-groups. In the first major clade the anzioid and usneoid clades formed a strongly supported sister-group relationship with the cetrarioid + hypogymnioid group. The sister-group relationship of Evernia with the cetrarioid clade was also strongly supported, whereas that between the anzioid and usneoid clades needs further investigation. In the second major clade Oropogon and Platismatia were sister to the parmelioid group, while the position of Omphalora was not fully resolved. This study demonstrates the power of genome-scale data sets to resolve long-standing, ambiguous phylogenetic relationships of lichen-forming fungi. Furthermore, the topology inferred in this study will provide a valuable framework for better understanding diversification in the most diverse lineage of lichen-forming fungi, Parmeliaceae.

Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent triple negative (TN) invasive carcinomas with poor prognosis. MBCs have a different clinical behavior from other types of triple negative breast cancer (TNBC), being more resistant to standard chemotherapy. MBCs are an example of tumors with activation of epithelial–mesenchymal transition (EMT). The mechanisms involved in EMT could be responsible for the increase in the infiltrative and metastatic capacity of MBCs and resistance to treatments. In addition, a relationship between EMT and the immune response has been seen in these tumors. In this sense, MBC differ from other TN tumors showing a lower number of tumor-infiltrating lymphocytes (TILS) and a higher percentage of tumor cells expressing programmed death-ligand 1 (PD-L1). A better understanding of the relationship between the immune system and EMT could provide new therapeutic approaches in MBC.

Cutaneous metastases (CMs) account for 2% of all skin malignancies, and nearly 70% of CMs in women originate from breast cancer (BC). CMs are usually associated with poor prognosis, are difficult to treat, and can pose diagnostic problems, such as in histopathological diagnosis when occurring long after development of the primary tumor. In addition, the molecular differences between the primary tumors and their CMs, and between CMs and metastases in other organs, are not well defined. Here, we review the main clinical, pathological, and molecular characteristics of breast cancer CMs. Identifying molecular markers in primary BC that predict CM and can be used to determine the molecular differences between primary tumors and their metastases is of great interest for the design of new therapeutic approaches.

Parmeliaceae is the largest family of lichen-forming fungi with a worldwide distribution. We used a target enrichment data set and a qualitative selection method for 250 out of 350 genes to infer the phylogeny of the major clades in this family including 81 taxa, with both subfamilies and all seven major clades previously recognized in the subfamily Parmelioideae. The reduced genome-scale data set was analyzed using concatenated-based Bayesian inference and two different Maximum Likelihood analyses, and a coalescent-based species tree method. The resulting topology was strongly supported with the majority of nodes being fully supported in all three concatenated-based analyses. The two subfamilies and each of the seven major clades in Parmelioideae were strongly supported as monophyletic. In addition, most backbone relationships in the topology were recovered with high nodal support. The genus Parmotrema was found to be polyphyletic and consequently, it is suggested to accept the genus Crespoa to accommodate the species previously placed in Parmotrema subgen. Crespoa. This study demonstrates the power of reduced genome-scale data sets to resolve phylogenetic relationships with high support. Due to lower costs, target enrichment methods provide a promising avenue for phylogenetic studies including larger taxonomic/specimen sampling than whole genome data would allow.

Fungal reproduction is regulated by the mating-type (MAT1) locus, which typically comprises two idiomorphic genes. The presence of one or both allelic variants at the locus determines the reproductive strategy in fungi-homothallism versus heterothallism. It has been hypothesized that self-fertility via homothallism is widespread in lichen-forming fungi. To test this hypothesis, we characterized the MAT1 locus of 41 genomes of lichen-forming fungi representing a wide range of growth forms and reproductive strategies in the class Lecanoromycetes, the largest group of lichen-forming fungi. Our results show the complete lack of genetic homothallism suggesting that lichens evolved from a heterothallic ancestor. We argue that this may be related to the symbiotic lifestyle of these fungi, and may be a key innovation that has contributed to the accelerated diversification rates in this fungal group.