The Phylogeny of Class B Flavoprotein Monooxygenases and the Origin of the YUCCA Protein Family.

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.

Evolution of Brain Active Gene Promoters in Human Lineage Towards the Increased Plasticity of Gene Regulation.

Adaptability to a variety of environmental conditions is a prominent feature of Homo sapiens. We hypothesize that this feature can be explained by evolutionary changes in gene promoters active in the brain prefrontal cortex leading to a more flexible gene regulation network. The genotype-dependent range of gene expression can be broader in humans than in other higher primates. Thus, we searched for specific signatures of evolutionary changes in promoter architectures of multiple hominid genes, including the genes active in human cortical neurons that may indicate an increase of variability of gene expression rather than just changes in the level of expression, such as downregulation or upregulation of the genes. We performed a whole-genome search for genetic-based alterations that may impact gene regulation "flexibility" in a process of hominids evolution, such as (i) CpG dinucleotide content, (ii) predicted nucleosome-DNA dissociation constant, and (iii) predicted affinities for TATA-binding protein (TBP) in gene promoters. We tested all putative promoter regions across the human genome and especially gene promoters in active chromatin state in neurons of prefrontal cortex, the brain region critical for abstract thinking and social and behavioral adaptation. Our data imply that the origin of modern man has been associated with an increase of flexibility of promoter-driven gene regulation in brain. In contrast, after splitting from the ancestral lineages of H. sapiens, the evolution of ape species is characterized by reduced flexibility of gene promoter functioning, underlying reduced variability of the gene expression.

Abundances of microRNAs in human cells can be estimated as a function of the abundances of YRHB and RHHK tetranucleotides in these microRNAs as an ill-posed inverse problem solution.

Mature microRNAs (miRNAs) are small endogenous non-coding RNAs 18-25 nt in length. They program the RNA Induced Silencing Complex (RISC) to make it inhibit either messenger RNAs or promoter DNAs. We have found that the mean abundance of miRNAs in Arabidopsis is correlated with the abundance of DRYD tetranucleotides near the 3'-end and the abundance of WRHB tetranucleotides in the center of the miRNA sequence. Based on this correlation, we have estimated miRNA abundances in seven organs of this plant, namely: inflorescences, stems, siliques, seedlings, roots, cauline, and rosette leaves. We have also found that the mean affinity of miRNAs for two proteins in the Argonaute family (Ago2 and Ago3) in man is correlated with the abundance of YRHB tetranucleotides near the 3'-end and that the preference of miRNAs for Ago2 is correlated with the abundance of RHHK tetranucleotides in the center of the miRNA sequence. This allowed us to obtain statistically significant estimates of miRNA abundances in human embryonic kidney cells, HEK293T. These findings in relation to two taxonomically distant entities (man and Arabidopsis) fit one another like pieces of a jigsaw puzzle, which allowed us to heuristically generalize them and state that the miRNA abundance in the human brain may be determined by the abundance of YRHB and RHHK tetranucleotides in these miRNAs.

Molecular evolution of cyclin proteins in animals and fungi.

BACKGROUND: 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. RESULTS: We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution. CONCLUSIONS: The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.

Computer System for Analysis of Molecular Evolution Modes (SAMEM): analysis of molecular evolution modes at deep inner branches of the phylogenetic tree.

SAMEM (System for Analysis of Molecular Evolution Modes), a web-based pipeline system for inferring modes of molecular evolution in genes and proteins (http://pixie.bionet.nsc.ru/samem/), is presented. Pipeline 1 performs analyses of protein-coding gene evolution; pipeline 2 performs analyses of protein evolution; pipeline 3 prepares datasets of genes and/or proteins, performs their primary analysis, and builds BLOSUM matrices; pipeline 4 checks if these genes really are protein-coding. Pipeline 1 has an all-new feature, which allows the user to obtain K(R)/K(C) estimates using several different methods. An important feature of pipeline 2 is an original method for analyzing the rates of amino acid substitutions at the branches of a phylogenetic tree. The method is based on Markov modeling and a non-parametric permutation test, which compares expected and observed frequencies of amino acid substitutions, and infers the modes of molecular evolution at deep inner branches.

SNPs in the HIV-1 TATA box and the AIDS pandemic.

Evolutionary trends have been examined in 146 HIV-1 forms (2662 copies, 2311 isolates) polymorphic for the TATA box using the "DNA sequence-->affinity for TBP" regression (TBP is the TATA binding protein). As a result, a statistically significant excess of low-affinity TATA box HIV-1 variants corresponding to a low level of both basal and TAT-dependent expression and, consequently, slow replication of HIV-1 have been detected. A detailed analysis revealed that the excess of slowly replicating HIV-1 is associated with the subtype E-associated TATA box core sequence "CATAAAA". Principal Component Analysis performed on 2662 HIV-1 TATA box copies in 70 countries revealed the presence of two principal components, PC1 (75.7% of the variance) and PC2 (23.3% of the variance). They indicate that each of these countries is specifically associated with one of the following trends in HIV-1 evolution: neutral drift around the normal TATA box; neutral drift around the slowly replicating TATA box core sequence (phylogenetic inertia); an adaptive increase in the frequency of the slowly replicating form.

Comparative modeling of coevolution in communities of unicellular organisms: adaptability and biodiversity.

We propose an original program "Evolutionary constructor" that is capable of computationally efficient modeling of both population-genetic and ecological problems, combining these directions in one model of required detail level. We also present results of comparative modeling of stability, adaptability and biodiversity dynamics in populations of unicellular haploid organisms which form symbiotic ecosystems. The advantages and disadvantages of two evolutionary strategies of biota formation--a few generalists' taxa-based biota formation and biodiversity-based biota formation--are discussed.

Simulation of coevolution in community by using the "Evolutionary Constructor" program.

An original modeling tool called Evolutionary Constructor has been proposed and described. Evolutionary Constructor combines the advantages of both generalized and portrait modeling and, additionally, provides an option to modify a current model's structure. The evolution of communities comprising atrophic ring-like network with the horizontal transfer of metabolism genes occurring among the communities has been modeled and presented. It has been demonstrated that a prolonged increase in the fitness of any single population that forms part of that trophic ring-like network of antagonistic communities will eventually lead that system to becoming absolutely dependent on environmental fluctuations. This result challenges the intuitive attitudes that the higher population fitness, the more stability is given to that population. Modeling of a system comprised by symbiotic communities has revealed that horizontal transfer confers a selective advantage not only on the acceptor population (which is up to expectations) but also on the donor population. It has therefore been demonstrated that horizontal transfer can be preserved by selection along evolution even without "selfish genes". Evolutionary Constructor can handle any phenotypic trait that is controlled genetically, epigenetically, etc., which extends the applicability of this tool to various processes of information transduction among populations, provided that these processes resemble horizontal gene transfer.