Search

ᅟ Some tumor cells can evolve into transmissible parasites. Notable examples include the Tasmanian devil facial tumor disease, the canine transmissible venereal tumor and transmissible cancers of mollusks. We present a hypothesis that such transmissible tumors existed in the past and that some modern animal taxa are descendants of these tumors. We expect potential candidates for SCANDALs (speciated by cancer development animals) to be simplified relatives of more complex metazoans and have genomic alterations typical for cancer progression (such as deletions of universal apoptosis genes). We considered several taxa of simplified animals for our hypothesis: dicyemida, orthonectida, myxosporea and trichoplax. Based on genomic analysis we conclude that Myxosporea appear to be the most suitable candidates for a tumor ancestry. They are simplified parasitic cnidarians that universally lack major genes implicated in cancer progression including all genes with Caspase and BCL2 domains as well as any p53 and apoptotic protease activating factor – 1 (Apaf-1) homologs, suggesting the disruption of main apoptotic pathways in their early evolutionary history. Further comparative genomics and single-cell transcriptomic studies may be helpful to test our hypothesis of speciation via a cancerous stage. Reviewers This article was reviewed by Eugene Koonin, Mikhail Gelfand and Gregory M Woods. Electronic supplementary material The online version of this article (10.1186/s13062-019-0233-1) contains supplementary material, which is available to authorized users.

Background SARS-CoV-2 is a novel coronavirus that causes COVID-19 infection, with a closest known relative found in bats. For this virus, hundreds of genomes have been sequenced. This data provides insights into SARS-CoV-2 adaptations, determinants of pathogenicity and mutation patterns. A comparison between patterns of mutations that occurred before and after SARS-CoV-2 jumped to human hosts may reveal important evolutionary consequences of zoonotic transmission. Methods We used publically available complete genomes of SARS-CoV-2 to calculate relative frequencies of single nucleotide variations. These frequencies were compared with relative substitutions frequencies between SARS-CoV-2 and related animal coronaviruses. A similar analysis was performed for human coronaviruses SARS-CoV and HKU1. Results We found a 9-fold excess of G–U transversions among SARS-CoV-2 mutations over relative substitution frequencies between SARS-CoV-2 and a close relative coronavirus from bats (RaTG13). This suggests that mutation patterns of SARS-CoV-2 have changed after transmission to humans. The excess of G–U transversions was much smaller in a similar analysis for SARS-CoV and non-existent for HKU1. Remarkably, we did not find a similar excess of complementary C–A mutations in SARS-CoV-2. We discuss possible explanations for these observations.

Inverted repeats are common DNA elements, but they rarely overlap with protein-coding sequences due to the ensuing conflict with the structure and function of the encoded protein. We discovered numerous perfect inverted repeats of considerable length (up to 284 bp) embedded within the protein-coding genes in mitochondrial genomes of four Nematomorpha species. Strikingly, both arms of the inverted repeats encode conserved regions of the amino acid sequence. We confirmed enzymatic activity of the respiratory complex I encoded by inverted repeat-containing genes. The nucleotide composition of inverted repeats suggests strong selection at the amino acid level in these regions. We conclude that the inverted repeat-containing genes are transcribed and translated into functional proteins. The survey of available mitochondrial genomes reveals that several other organisms possess similar albeit shorter embedded repeats. Mitochondrial genomes of Nematomorpha demonstrate an extraordinary evolutionary compromise where protein function and stringent secondary structure elements within the coding regions are preserved simultaneously.

Two enigmatic groups of morphologically simple parasites of invertebrates, the Dicyemida (syn. Rhombozoa) and the Orthonectida, since the 19th century have been usually considered as two classes of the phylum Mesozoa. Early molecular evidence suggested their relationship within the Spiralia (=Lophotrochozoa), however, high rates of dicyemid and orthonectid sequence evolution led to contradicting phylogeny reconstructions. Genomic data for orthonectids revealed that they are highly simplified spiralians and possess a reduced set of genes involved in metazoan development and body patterning. Acquiring genomic data for dicyemids, however, remains a challenge due to complex genome rearrangements including chromatin diminution and generation of extrachromosomal circular DNAs, which are reported to occur during the development of somatic cells. We performed genomic sequencing of one species of Dicyema, and obtained transcriptomic data for two Dicyema spp. Homeodomain (homeobox) transcription factors, G-protein-coupled receptors, and many other protein families have undergone a massive reduction in dicyemids compared to other animals. There is also apparent reduction of the bilaterian gene complements encoding components of the neuromuscular systems. We constructed and analyzed a large dataset of predicted orthologous proteins from three species of Dicyema and a set of spiralian animals including the newly sequenced genome of the orthonectid Intoshia linei. Bayesian analyses recovered the orthonectid lineage within the Annelida. In contrast, dicyemids form a separate clade with weak affinity to the Rouphozoa (Platyhelminthes plus Gastrotricha) or (Entoprocta plus Cycliophora) suggesting that the historically proposed Mesozoa is a polyphyletic taxon. Thus, dramatic simplification of body plans in dicyemids and orthonectids, as well as their intricate life cycles that combine metagenesis and heterogony, evolved independently in these two lineages.

Summary Orthonectids are rare parasites of marine invertebrates [1] that are commonly treated in textbooks as a taxon of uncertain affinity [2]. Trophic forms of orthonectids reside in the tissues of their hosts as multinucleated plasmodia, generating short-lived, worm-like ciliated female and male organisms that exit into the environment for copulation [3]. These ephemeral males and females are composed of just several hundred somatic cells and are deprived of digestive, circulatory, or excretory systems. Since their discovery in the 19 th century, the orthonectids were described as organisms with no differentiated cell types and considered as part of Mesozoa, a putative link between multicellular animals and their unicellular relatives. More recently, this view was challenged as the new data suggested that orthonectids are animals that became simplified due to their parasitic way of life [3, 4]. Here, we report the genomic sequence of Intoshia linei , one of about 20 known species of orthonectids. The genomic data confirm recent morphological analysis asserting that orthonectids are members of Spiralia and possess muscular and nervous systems [5]. The 43-Mbp genome of I. linei encodes about 9,000 genes and retains those essential for the development and activity of muscular and nervous systems. The simplification of orthonectid body plan is associated with considerable reduction of metazoan developmental genes, leaving what might be viewed as the minimal gene set necessary to retain critical bilaterian features.

Many features of mitochondrial genomes of animals, such as patterns of gene arrangement, nucleotide content and substitution rate variation are extensively used in evolutionary and phylogenetic studies. Nearly 6,000 mitochondrial genomes of animals have already been sequenced, covering the majority of animal phyla. One of the groups that escaped mitogenome sequencing is phylum Kinorhyncha-an isolated taxon of microscopic worm-like ecdysozoans. The kinorhynchs are thought to be one of the early-branching lineages of Ecdysozoa, and their mitochondrial genomes may be important for resolving evolutionary relations between major animal taxa. Here we present the results of sequencing and analysis of mitochondrial genomes from two members of Kinorhyncha, Echinoderes svetlanae (Cyclorhagida) and Pycnophyes kielensis (Allomalorhagida). Their mitochondrial genomes are circular molecules approximately 15 Kbp in size. The kinorhynch mitochondrial gene sequences are highly divergent, which precludes accurate phylogenetic inference. The mitogenomes of both species encode a typical metazoan complement of 37 genes, which are all positioned on the major strand, but the gene order is distinct and unique among Ecdysozoa or animals as a whole. We predict four types of start codons for protein-coding genes in E. svetlanae and five in P. kielensis with a consensus DTD in single letter code. The mitochondrial genomes of E. svetlanae and P. kielensis encode duplicated methionine tRNA genes that display compensatory nucleotide substitutions. Two distant species of Kinorhyncha demonstrate similar patterns of gene arrangements in their mitogenomes. Both genomes have duplicated methionine tRNA genes; the duplication predates the divergence of two species. The kinorhynchs share a few features pertaining to gene order that align them with Priapulida. Gene order analysis reveals that gene arrangement specific of Priapulida may be ancestral for Scalidophora, Ecdysozoa, and even Protostomia.

Expression of the Panx1 and Panx2 members of the pannexin family of gap junction proteins was studied in the retina by in situ hybridization and qRT-PCR. Both pannexins showed robust expression across the retina with predominant accumulation in the retinal ganglion cells (RGCs). In concordance, immunohistochemical analysis showed accumulation of the Panx1 protein in RGCs, amacrine, horizontal cells and their processes. Two Panx1 isoforms were detected: a ubiquitously expressed 58kDa protein, and a 43kDa isoform that specifically accumulated in the retina and brain. Our results indicated that Panx1 and Panx2 are abundantly expressed in the retina, and may therefore contribute to the electrical and metabolic coupling, or to signaling between retinal neurons via the secondary messengers.

Early cleavages of the marine nematode Enoplus brevis are symmetrical and occur in synchrony. At the 2- to 16-cell stages, blastomeres are indistinguishable. The progeny of blastomeres was investigated by intracellular injections of fluorescent dyes and horse radish peroxidase. One blastomere of the 2-cell embryo gives rise to a compact group of cells occupying about half of an embryo. The border between labeled and unlabeled cells differs in each embryo dividing it to anterior-posterior, left-right or intermediate parts. At the 8-cell stage, one blastomere gives rise to only endoderm, whereas the other blastomeres produce progeny that form multiple cell types, including nerve, muscle and hypoderm cells, in various proportions. Thus the fates of the blastomeres of early E. brevis embryos, with the exception of the endoderm precursor, are not determined. The process of gastrulation in E. brevis is very similar to that in Caenorhabditis elegans and other nematodes. At the beginning of gastrulation, the 2-celled endoderm precursor lies on the surface of embryo and then sinks inwards. After labeling of cells on the ventral side (near endoderm precursor) at the beginning of gastrulation, their progeny differentiate predominantly into body muscles or pharyngeal cells of the first stage larva. Cells that are located more laterally give rise mainly to neurons. The dorsal blastomeres differentiated principally into hypoderm cells. Our study suggests that a precise cell lineage is not a necessary attribute of nematode development.

According to much quoted Russian/American geneticist Theodosius Dobzhansky, “Nothing in biology makes sense except in the light of evolution” [1]. Coined in 1973, this famous phrase remains up to date. Fascinating variety of the phenotypes seen as either visible or subtle differences in species, populations, and individual organisms inhabiting our planet attracts an unwavering inquiry. The results of these inquiries are shedding some light both at intricate molecular programs continuously executed within living bodies and at checks and balances within homeostatic ecosystems. In fact, every transformative technology so far invented to improve human medicine or other areas of applied science was immediately embraced by traditional biologists and contributed to the extraction of evolutionary insights. Some years ago, that happened with PCR. Recently, we entered systems biology driven turn of an inquiry spiral. This turn is enabled by an advent of NextGen sequencing. Importantly, a few final steps on this spiral became computationally heavy. Hence, the aid of bioinformatics was summoned, and computationally derived conclusions came in droves. While the mining of completed genomes remains an obvious source is information on evolutionary processes, we also see the emergence of a novel kind of the full-genome studies, ones that aim at the tinkering with the evolutionary theory itself. By their scale and potential, these studies may be compared to the two previous technological developments that changed the history of evolutionary studies. The first of these methodological revolutions is a comparative analysis of traits that was started by Lamarck [2] and Darwin [3] and still is a source of novel evolutionary inferences. The second one was the introduction of the molecular analysis (see [4]) that approximately coincided with the establishment of the synthetic theory of evolution. Since that, the methods of the analysis of molecular traits kept progressing. By now, it is clear that molecular-based inquiry opened whole new field of questions which may be asked and answered, for example, one that relates to the evolution of the intracellular parasites, microbial communities, or populations of the cells within human body burdened with a tumor. The introduction of NextGen sequencing dramatically increased the amount of information that may be extracted from the sample of biological material and added the whole new level of integration of organismal data, thus enabling the systems biology in its true sense. Nowadays, one may be certain that widespread adoption of NextGen sequencing will uplift the evolutionary theory to new heights, however, where will it bring us even in next few years is substantially harder to predict. We should not forget that evolutionary genomics is still an emerging field in biology. For now, it does not have a road map, a master plan, or even a template—one who starts the analysis of data collected from the study of living system never knows where this analysis might end. This volume is yet another attempt to provide a bird's view at bioinformatics-driven forays into the field of evolutionary biology. However, it is an opinion of the Editors that presented eclectic collection of papers is not without its merits. In case of existing data, even a mere push to extract an evolutionary insight enables the scientist to see the pattern that would be very difficult to discern otherwise. So much better it is for the studies specifically designed to solve one or another biological enigma. In this issue, we are glad to present an eclectic collection of papers that cover a range of topics from analysis of intron evolution across kingdoms to the study of the divergence in salmonid species and to comparative genomics of cancer-specific genes. These manuscripts are a sampler of future insights yet to come from the troves of genome sequences thoroughly dissected with bioinformatics tools. Enjoy! Dmitry Sherbakov Yuri Panchin Ancha Baranova

Substitution rates strongly depend on their nucleotide context. One of the most studied examples is the excess of C > T mutations in the CG context in various groups of organisms, including vertebrates. Studies on the molecular mechanisms underlying this mutation regularity have provided insights into evolution, mutagenesis, and cancer development. Recently several other hypermutable motifs were identified in the human genome. There is an increased frequency of T > C mutations in the second position of the words ATTG and ATAG and an increased frequency of A > C mutations in the first position of the word ACAA. For a better understanding of evolution, it is of interest whether these mutation regularities are human specific or present in other vertebrates, as their presence might affect the validity of currently used substitution models and molecular clocks. A comprehensive analysis of mutagenesis in 4 bp mutation contexts requires a vast amount of mutation data. Such data may be derived from the comparisons of individual genomes or from single nucleotide polymorphism (SNP) databases. Using this approach, we performed a systematical comparison of mutation regularities within 2–4 bp contexts inMus musculusandHomo sapiensand uncovered that even closely related organisms may have notable differences in context-dependent mutation regularities.

In general, mutation frequencies are context-dependent: specific adjacent nucleotides may influence the probability to observe a specific type of mutation in a genome. Recently, several hypermutable motifs were identified in the human genome. Namely, there is an increased frequency of T>C mutations in the second position of the words ATTG and ATAG and an increased frequency of A>C mutations in the first position of the word ACAA. Previous studies have also shown that there is a remarkable difference between the mutagenesis of humans and drosophila. While C>T mutations are overrepresented in the CG context in humans (and other vertebrates), this mutation regularity is not observed inDrosophila melanogaster. Such differences in the observed regularities of mutagenesis between representatives of different taxa might reflect differences in the mechanisms involved in mutagenesis. We performed a systematical comparison of mutation regularities within 2–4 bp contexts inHomo sapiensandDrosophila melanogasterand found that the aforementioned contexts are not hypermutable in fruit flies. It seems that most mutation contexts affect mutation rates in a similar manner inH. sapiensandD. melanogaster; however, several important exceptions are noted and discussed.

Animal genomes contain approximately 20,000 genes. Additionally millions of genes for antigen receptors are generated in cells of the immune system from the sets of separate gene segments by a mechanism known as the V(D)J somatic recombination. The components of the V(D)J recombination system, Recombination-Activating Gene proteins (RAG1 and RAG2) and recombination signal sequence (RSS), are thought to have "entered" the vertebrate genome as a hypothetical "RAG transposon". Recently discovered mobile elements have terminal inverted repeats (TIRs) similar to RSS and may encode proteins with a different degree of similarity to RAG1. We describe a novel N-RAG-TP transposon identified from the sea slug Aplysia californica that encodes a protein similar to the N-terminal part of RAG1 in vertebrates. This refines the "RAG transposon" hypothesis and allows us to propose a scenario for V(D)J recombination machinery evolution from a relic transposon related to the existing mobile elements N-RAG-TP, Chapaev, and Transib.

Expressed sequence tags (ESTs) represent 500–1000-bp-long sequences corresponding to mRNAs derived from different sources (cell lines, tissues, etc.). The human EST database contains over 8,000,000 sequences, with over 4,000,000,000 total nucleotides. RNA molecules are transcribed from a genomic DNA template; therefore, all ESTs should match corresponding genomes. Nevertheless, we have found in the human EST database approximately 11,000 ESTs not matching sequences in the human genome database. The presence of "trash" ESTs (TESTs) in the EST database could result from DNA or RNA contamination of the laboratory equipment, tissues, or cell lines. TESTs could also represent sequences from unidentified human genes or from species inhabiting the human body. Here, we attempt to identify the sources of human EST database contaminations. In particular, we discuss systematic contamination of the mammalian EST databases with sequences of plants.

Background The substitution rates within different nucleotide contexts are subject to varying levels of bias. The most well known example of such bias is the excess of C to T (C > T) mutations in CpG (CG) dinucleotides. The molecular mechanisms underlying this bias are important factors in human genome evolution and cancer development. The discovery of other nucleotide contexts that have profound effects on substitution rates can improve our understanding of how mutations are acquired, and why mutation hotspots exist. Results We compared rates of inherited mutations in 1-4 bp nucleotide contexts using reconstructed ancestral states of human single nucleotide polymorphisms (SNPs) from intergenic regions. Chimp and orangutan genomic sequences were used as outgroups. We uncovered 3.5 and 3.3-fold excesses of T > C mutations in the second position of ATTG and ATAG words, respectively, and a 3.4-fold excess of A > C mutations in the first position of the ACAA word. Conclusions Although all the observed biases are less pronounced than the 5.1-fold excess of C > T mutations in CG dinucleotides, the three 4 bp mutation contexts mentioned above (and their complementary contexts) are well distinguished from all other mutation contexts. This provides a challenge to discover the underlying mechanisms responsible for the observed excesses of mutations.