Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.

The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi.

YUCCA (YUCCA flavin-dependent monooxygenase) is one of the two enzymes of the main auxin biosynthesis pathway (tryptophan aminotransferase enzyme (TAA)/YUCCA) in land plants. The evolutionary origin of the YUCCA family is currently controversial: YUCCAs are assumed to have emerged via a horizontal gene transfer (HGT) from bacteria to the most recent common ancestor (MRCA) of land plants or to have inherited it from their ancestor, the charophyte algae. To refine YUCCA origin, we performed a phylogenetic analysis of the class B flavoprotein monooxygenases and comparative analysis of the sequences belonging to different families of this protein class. We distinguished a new protein family, named type IIb flavin-containing monooxygenases (FMOs), which comprises homologs of YUCCA from Rhodophyta, Chlorophyta, and Charophyta, land plant proteins, and FMO-E, -F, and -G of the bacterium Rhodococcus jostii RHA1. The type IIb FMOs differ considerably in the sites and domain composition from the other families of class B flavoprotein monooxygenases, YUCCAs included. The phylogenetic analysis also demonstrated that the type IIb FMO clade is not a sibling clade of YUCCAs. We have also identified the bacterial protein group named YUC-like FMOs as the closest to YUCCA homologs. Our results support the hypothesis of the emergence of YUCCA via HGT from bacteria to MRCA of land plants.

Phospholipases A2 (PLA2) are capable of hydrolyzing the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids. The PLA2 superfamily enzymes are widespread and present in most mammalian cells and tissues, regulating metabolism, remodeling the membrane and maintaining its homeostasis, producing lipid mediators and activating inflammatory reactions, so disruption of PLA2-regulated lipid metabolism often leads to various diseases. In this study, 29 PLA2 genes in the human genome were systematically collected and described based on literature and sequence analyses. Localization of the PLA2 genes in human genome showed they are placed on 12 human chromosomes, some of them forming clusters. Their RVI scores estimating gene tolerance to the mutations that accumulate in the human population demonstrated that the G4-type PLA2 genes belonging to one of the two largest clusters (4 genes) were most tolerant. On the contrary, the genes encoding G6-type PLA2s (G6B, G6F, G6C, G6A) localized outside the clusters had a reduced tolerance to mutations. Analysis of the association between PLA2 genes and human diseases found in the literature showed 24 such genes were associated with 119 diseases belonging to 18 groups, so in total 229 disease/PLA2 gene relationships were described to reveal that G4, G2 and G7-type PLA2 proteins were involved in the largest number of diseases if compared to other PLA2 types. Three groups of diseases turned out to be associated with the greatest number of PLA2 types: neoplasms, circulatory and endocrine system diseases. Phylogenetic analysis showed that a common origin can be established only for secretory PLA2s (G1, G2, G3, G5, G10 and G12). The remaining PLA2 types (G4, G6, G7, G8, G15 and G16) could be considered evolutionarily independent. Our study has found that the genes most tolerant to PLA2 mutations in humans (G4, G2, and G7 types) belong to the largest number of disease groups.

The tryptophan biosynthesis pathway is universal for the majority of known organisms, although it is absent in animals and some eubacteria. This pathway is conserved in plants, although various species differ in the number of paralogs of the enzymes involved in it. In this work, the possible role of the changes in the number of tryptophan biosynthesis enzymes paralogs in the course of evolution was analyzed. Towards this, the paralogs of the enzymes in tryptophan biosynthesis pathways were identified in plant species with fully sequenced genomes, and the relationship between the number of paralogs and the organismal complexity was assessed. It was demonstrated that organismal complexity statistically correlates with the number of tryptophan biosynthesis enzymes homologs, both with the total number of homologs and with the number of homologs for three of six enzymes, namely, ASA/ASB, PAI, and IGPS. This relationship may be accounted for by the increase in the organismal complexity and the number of tryptophan biosynthesis enzymes’ homologs being the mechanism of evolutionary adaptation to the varying conditions of the terrestrial environment in plants.

The phospholipase A2 (PLA2) is a superfamily of hydrolases that catalyze the hydrolysis of phospholipids and play a key role in many molecular processes in the cells and the organism as a whole. This family consists of 16 groups divided into six main types. PLA2 were first isolated from venom toxins and porcine pancreatic juice. The study of these enzymes is currently of great interest, since it has been shown that a number of PLA2 are involved in the processes of carcinogenesis. PLA2 enzymes were characterized in detail in model organisms and humans. However, their presence and functional role in non-model organisms is poorly understood. Such poorly studied taxa include flatworms, a number of species of which are human parasites. Several PLA2 genes have previously been characterized in parasitic flatworms and their possible role in parasite-host interaction has been shown. However, no systematic identification of the PLA2 genes in this taxon has been carried out. The paper provides a search for and a comparative analysis of PLA2 sequences encoded in the genomes of flatworms. 44 species represented by two free-living and 42 parasitic organisms were studied. The analysis was based on identification of orthologous groups of protein-coding genes, taking into account the domain structure of proteins. In flatworms, 12 of the 13 known types of animal A2 phospholipases were found, represented by 11 orthologous groups. Some phospholipases of several types fell into one orthologous group, some types split into several orthogroups in accordance with their domain structure. It has been shown that phospholipases A2 of the calcium-independent type, platelet-activating phospho­lipases from group G8 and lysosomal phospholipases from group G15 are represented in all large taxa of flatworms and the vast majority of the species studied by us. In free-living flatworms PLA2 genes have multiple copies. In parasitic flatworms, on the contrary, loss of genes occur specifically in individual taxa specifically for groups or sub­families of PLAs. An orthologous group of secreted phospholipases has been identified, which is represented only in Digenea and this family has undergone duplications in the genomes of opisthorchids. Interestingly, a number of experimental studies have previously shown the effect of Clonorchis sinensis proteins of this orthogroup on the cancer transformation of host cells. Our results made it possible for the first time to systematically identify PLA2 sequences in flatworms, and demonstrated that their evolution is subject to gene loss processes characteristic of parasite genomes in general. In addition, our analysis allowed us to identify taxon-specific processes of duplication and loss of PLA2 genes in parasitic organisms, which may be associated with the processes of their interaction with the host organism.