On the origin and evolution of new genes——a genomic and experimental perspective

The inherent interest on the origin of genetic novelties can be traced back to Darwin, But it was not until recently that we were allowed to investigate the fundamental process of origin of new genes by the studies on newly evolved young genes. Two indispensible steps are involved in this process: origin of new gene copies through various mutational mechanisms and evolution of novel functions, which fur-ther more leads to fixation of the new copies within populations. The theoretical framework for the former step formed in 1970s. Ohno proposed gene duplication as the most important mechanism producing new gene copies. He also believed that the most common fate for new gene copies is to become pseudogenes. This classical view was validated and was also challenged by the characterization of the first functional young gene jingwei in Drosophila. Recent genome-wide comparison on young genes of Drosophila has elucidated a compre-hensive picture addressing remarkable roles of various mechanisms besides gene duplication during origin of new genes. Case surveys revealed it is not rare that new genes would evolve novel structures and functions to contribute to the adaptive evolution of organisms.Here, we review recent advances in understanding how new genes originated and evolved on the basis of genome-wide results and ex-perimental efforts on cases, We would finally discuss the future directions of this fast-growing research field in the context of functional genomics era.     

Prediction of novel microRNA genes in cancer-associated genomic regions—a combined computational and experimental approach

The majority of existing computational tools rely on sequence homology and/or structural similarity to identify novel microRNA (miRNA) genes. Recently supervised algorithms are utilized to address this problem, taking into account sequence, structure and comparative genomics information. In most of these studies miRNA gene predictions are rarely supported by experimental evidence and prediction accuracy remains uncertain. In this work we present a new computational tool (SSCprofiler) utilizing a probabilistic method based on Profile Hidden Markov Models to predict novel miRNA precursors. Via the simultaneous integration of biological features such as sequence, structure and conservation, SSCprofiler achieves a performance accuracy of 88.95% sensitivity and 84.16% specificity on a large set of human miRNA genes. The trained classifier is used to identify novel miRNA gene candidates located within cancer-associated genomic regions and rank the resulting predictions using expression information from a full genome tiling array. Finally, four of the top scoring predictions are verified experimentally using northern blot analysis. Our work combines both analytical and experimental techniques to show that SSCprofiler is a highly accurate tool which can be used to identify novel miRNA gene candidates in the human genome. SSCprofiler is freely available as a web service at http://www.imbb.forth.gr/SSCprofiler.html.     

Comparative genomic analysis of the proteasome β5t subunit gene: implications for the origin and evolution of thymoproteasomes

The thymoproteasome is a recently discovered, specialized form of 20S proteasomes expressed exclusively in the thymic cortex. Although the precise molecular mechanism by which the thymoproteasome exerts its function remains to be elucidated, accumulating evidence indicates that it plays a crucial role in positive selection of T cells. In the present study, we analyzed the evolution of the β5t subunit, a β-type catalytic subunit uniquely present in thymoproteasomes. The gene coding for the β5t subunit, designated PSMB11, was identified in the cartilaginous fish, the most divergent group of jawed vertebrates compared to the other jawed vertebrates, but not in jawless vertebrates or invertebrates. Interestingly, teleost fish have two copies of apparently functional PSMB11 genes, designated PSMB11a and PSMB11b, that encode β5t subunits with distinct amino acids in the S1 pocket. BLAST searches of genome databases suggest that birds such as chickens, turkey, and zebra finch lost the PSMB11 gene, and have neither thymoproteasomes nor immunoproteasomes. In mammals, reptiles, amphibians, and teleost fishes, the PSMB11 gene (the PSMB11a gene in teleost fish) is located next to the PSMB5 gene coding for the β5 subunit of the standard 20S proteasome, indicating that the PSMB11 gene arose by tandem duplication from the evolutionarily more ancient PSMB5 gene. The general absence of introns in PSMB11 and an unusual exon–intron structure of jawed vertebrate PSMB5 suggest that PSMB5 lost introns and duplicated in tandem in a common ancestor of jawed vertebrates, with PSMB5 subsequently gaining two introns and PSMB11 remaining intronless.     

On the origin ofVeronica persica (Scrophulariaceae)—a contribution to the history of a neophytic weed

A character analysis reveals a clearly intermediate position of the tetraploidV. persica (2n = 28) between the two diploid speciesV. polita andV. ceratocarpa (both 2n = 14) which are morphologically rather different and have been placed by several authors in different sections of the genus.V. ceratocarpa is native to subhumid deciduous forests of the Caucasus and of the Elburz mountains (N. Iran);V. polita has its centre of variation in the Elburz range where it grows in therophyte habitats. Three other closely related species,V. bungei, V. siaretensis, andV. francispetae, are endemic to the Elburz range which is the main centre of diversity and variability of theV. agrestis group. This comprises all the above mentioned species and also two more European weeds:V. agrestis andV. opaca. Veronica polita, was probably originally native to open places in deciduous mountain forests, before becoming a weed in neolithic times and migrating to Europe; nowadays it has an almost world-wide distribution. The allotetraploidV. persica combines the ecological characters of its parents, the slightly xerophyticV. polita and the more mesophyticV. ceratocarpa, thus being preadapted to become a highly successful weed with a large ecological range. It has spread rapidly almost all over the world since the early 19th century.Dedicated to Hofrat Univ.-Prof. DrKarl Heinz Rechinger on the occasion of the 80th anniversary of his birthday.     

Do we understand the evolution of genomic imprinting?

The conflict theory is the only hypothesis to have attracted any critical attention for the evolution of genomic imprinting. Although the earliest data appeared supportive, recent systematic analyses have not confirmed the model's predictions. The status of theory remains undecided, however, as post-hoc explanation can be provided as to why these predictions are not borne out.     

The stele – a developmental perspective on the diversity and evolution of primary vascular architecture

The stele concept is one of the oldest enduring concepts in plant biology. Here, I review the history of the concept and build an argument for an updated view of steles and their evolution. Studies of stelar organization have generated a widely ranging array of definitions that determine the way we classify steles and construct scenarios about the evolution of stelar architecture. Because at the organismal level biological evolution proceeds by changes in development, concepts of structure need to be grounded in development to be relevant in an evolutionary perspective. For the stele, most traditional definitions that incorporate development have viewed it as the totality of tissues that either originate from procambium – currently the prevailing view – or are bordered by a boundary layer (e.g. endodermis). Consensus between these two perspectives can be reached by recasting the stele as a structural entity of dual nature. Following a brief review of the history of the stele concept, basic terminology related to stelar organization, and traditional classifications of the steles, I revisit boundary layers from the perspective of histogenesis as a dynamic mosaic of developmental domains. I review anatomical and molecular data to explore and reaffirm the importance of boundary layers for stelar organization. Drawing on information from comparative anatomy, developmental regulation, and the fossil record, I propose a stele concept that integrates both the boundary layer and the procambial perspectives, consistent with a dual nature of the stele. This dual stele model posits that stelar architecture is determined at the apical meristem by two major cell fate specification events: a first one that specifies a provascular domain and its boundaries, and a second event that specifies a procambial domain (which will mature into conducting tissues) from cell subpopulations of the provascular domain. If the position and extent of the developmental domains defined by the two events are determined by different concentrations of the same morphogen (most likely auxin), then the distribution of this organizer factor in the shoot apical meristem, as modulated by changes in axis size and the effect of lateral organs, can explain the different stelar configurations documented among tracheophytes. This model provides working hypotheses that incorporate assumptions and generate implications that can be tested empirically. The model also offers criteria for an updated classification of steles in line with current understanding of plant development. In this classification, steles fall into two major categories determined by the configuration of boundary layers: boundary protosteles and boundary siphonosteles, each with subtypes defined by the architecture of the vascular tissues. Validation of the dual stele model and, more generally, in-depth understanding of the regulation of stelar architecture, will necessitate targeted efforts in two areas: (i) the regulation of procambium, vascular tissue, and boundary layer specification in all extant vascular plants, considering that most of the diversity in stelar architecture is hosted by seed-free plants, which are the least explored in terms of developmental regulation; (ii) the configuration of vascular tissues and, especially, boundary layers, in as many extinct lineages as possible.     

AIDS as a zoonosis? Confusion over the origin of the virus and the origin of the epidemics

Based on findings demonstrating the simian ancestry of HIV, AIDS has been reported to be a zoonosis. However, this theory has never been proved and must seriously be questioned. Several arguments show that HIV-AIDS is not a zoonosis. (i) If AIDS were a zoonosis, there must be evidence of AIDS being directly acquired from an animal species, as is rabies, a disease that is directly acquired from animals. (ii) Despite long-term and frequent human exposure to SIV-infected monkeys in Africa, only 11 cross-species transmission events are known, and only four of these have resulted in significant human-to-human transmission, generating HIV-1 groups M and O and HIV-2 groups A and B. The closest relatives of SIVcpz (HIV-1 group N) and of SIVsm (HIV-2 groups C-H) are extremely rare, with only six HIV-1 group N-infected patients and only single individuals known to be infected by HIV-2 groups C-H. SIV, while capable of cross-species transmission, is thus poorly adapted for disease and epidemic spread. If AIDS were a zoonosis that is capable of significant human-to-human spread, there would be a plethora of founder subtypes and groups. (iii) Human exposure to SIV is thousands of years old, but AIDS emerged only in the 20th century. If AIDS were a zoonosis that spread into the human population, it would have spread to the West during slave trade. (iv) Experimental transmission of SIVs to different species of monkeys is often well controlled by the new host, showing that the virus and not the disease is transmitted. Therefore, we conclude that cross-species transmission of SIV does not in itself constitute the basis for a zoonosis. Transmission per se is not the major requirement for the generation of the AIDS epidemic. All HIVs do derive from simian species, but AIDS does not qualify as a zoonosis and this explanation cannot in itself account for the origin of AIDS epidemic. It is important to distinguish AIDS from true zoonoses (e.g. rabies) because research is needed to understand the processes by which animal viruses cause sustained human-to-human transmission, epidemics and even pandemics. Much is known about emerging viruses, but almost nothing is known about emerging viral diseases.     

On the origin of SARS-CoV-2——The blind watchmaker argument

正In the comparison with SARS-CoVof 2003, SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive. By the blind watchmaker argument, such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.     

From proto-mitosis to mitosis — An alternative hypothesis on the origin and evolution of the mitotic spindle

Based on the assumption that the ancestral proto-eukaryote evolved from an ameboid prokarybte I propose the hypothesis that nuclear division of the proto-eukaryote was effected by the same system of contractile filaments it used for ameboid movement and cytosis. When the nuclear membranes evolved from the cell membrane, contractile filaments remained associated with them. The attachment site of the genome in the nuclear envelope was linked to the cell membrane by specialized contractile filaments. During protomitosis, i.e., nuclear and cell division of the proto-eukaryote, these filaments performed segregation of the chromosomes, whereas others constricted and cleaved the nucleus and the mother cell. When microtubules (MTs) had evolved in the cytoplasm, they also became engaged in nuclear division. Initially, an extranuolear bundle of MTs assisted chromosome segregation by establishing a defined axis. The evolutionary tendency then was towards an increasingly important role for MTs. Spindle pole bodies (SPBs) developed from the chromosomal attachment sites in the nuclear envelope and organized an extranuclear central spindle. The chromosomes remained attached to the SPBs during nuclear division. In a subsequent step the spindle became permanently lodged inside the nucleus. Chromosomes detached from the SPBs and acquired kinetochores and kinetochore-MTs. At first, this spindle segregated chromosomes by elongation, the kinetochore-MTs playing the role of static anchors. Later, spindle elongation was supplemented by poleward movement of the chromosomes. When dissolution of the nuclear envelope at the beginning of mitosis became a permanent feature, the open spindle of higher eukaryotes was born.     

Physiological and genomic characterization of a new ‘Candidatus Nitrotoga’ isolate

Oxidation of nitrite to nitrate is an important process in the global nitrogen cycle. Recent molecular biology-based studies have revealed that the widespread nitrite-oxidizing bacteria (NOB) belonging to the genus ‘Candidatus Nitrotoga’ may be highly important for the environment. However, the insufficient availability of pure Nitrotoga cultures has limited our understanding of their physiological and genomic characteristics. Here, we isolated the ‘Ca. Nitrotoga’ sp. strain AM1P, from a previously enriched Nitrotoga culture, using an improved isolation strategy. Although ‘Ca. Nitrotoga’ have been recognized as cold-adapted NOB, the strain AM1P had a slightly higher optimum growth temperature at 23°C. Strain AM1P showed a pH optimum of 8.3 and was not inhibited even at high nitrite concentrations (20 mM). We obtained the complete genome of the strain and compared the genome profile to five previously sequenced ‘Ca. Nitrotoga’ strains. Comparative genomics suggested that lactate dehydrogenase may be only encoded in the strain AM1P and closely related genomes. While the growth yield of AM1P did not change, we observed faster growth in the presence of lactate in comparison to purely chemolithoautotrophic growth. The characterization of the new strain AM1P sheds light on the physiological adaptation of this environmentally important, but understudied genus ‘Ca. Nitrotoga’.     

The β-tubulin gene family of pea: Primary structures,genomic organization and intron-dependent evolution of genes

One gene and two cDNAs encoding three different -tubulins (TUB1, TUB2, TUB3) of pea have been cloned and sequenced. The derived amino acid sequences show between 92% and 96% identity relative to one another and to most other -tubulins of higher plants and green algae. Two notable extremes are the high similarity of 98% between pea TUB3 and maize -tubulin 2 and the relatively low similarity (90%) of the hypocotyl-specific -tubulin 1 of soybean to the pea sequences. These similarities do not reflect the molecular phylogeny but rather differences in evolutionary rate of -tubulins which are differentially regulated during plant development. Genomic Southern blots reveal a -tubulin gene family in pea with at least four separate members including two TUB1 genes, one TUB2 gene and one TUB3 gene. This contradicts an earlier report by Rahaet al. (Plant Mol Biol 9: 565–571, 1987) suggesting a tandem repeat organization of tubulin genes in pea. The pea TUB1 gene has two introns in identical positions compared to the -tubulin genes fromArabidopsis and soybean. In an attempt to reconstruct the universal ancestor of all present-day tubulin genes the intron positions in 38 different - and -tubulin genes from plants, animals, fungi and protozoa were compared. This comparison shows that the primordial gene probably had many introns (more than 20) separating protoexons of 15 to 20 codons in agreement with the exon theory of genes. It also supports the view that, during the course of evolutions introns have shifted and were deleted preferentially in the 3 part of the genes. Similar observations have been made previously for other genes. They can be interpreted in terms of a homologous recombination of genes with their modified (incorrectly spliced) and reverse-transcribed pre-mRNAs.     

Origin and evolution of the panarthropod head – A palaeobiological and developmental perspective

The panarthropod head represents a complex body region that has evolved through the integration and functional specialization of the anterior appendage-bearing segments. Advances in the developmental biology of diverse extant organisms have led to a substantial clarity regarding the relationships of segmental homology between Onychophora (velvet worms), Tardigrada (water bears), and Euarthropoda (e.g. arachnids, myriapods, crustaceans, hexapods). The improved understanding of the segmental organization in panarthropods offers a novel perspective for interpreting the ubiquitous Cambrian fossil record of these successful animals. A combined palaeobiological and developmental approach to the study of the panarthropod head through deep time leads us to propose a consensus hypothesis for the intricate evolutionary history of this important tagma. The contribution of exceptionally preserved brains in Cambrian fossils – together with the recognition of segmentally informative morphological characters – illuminate the polarity for major anatomical features. The euarthropod stem-lineage provides a detailed view of the step-wise acquisition of critical characters, including the origin of a multiappendicular head formed by the fusion of several segments, and the transformation of the ancestral protocerebral limb pair into the labrum, following the postero-ventral migration of the mouth opening. Stem-group onychophorans demonstrate an independent ventral migration of the mouth and development of a multisegmented head, as well as the differentiation of the deutocerebral limbs as expressed in extant representatives. The anterior organization of crown-group Tardigrada retains several ancestral features, such as an anterior-facing mouth and one-segmented head. The proposed model aims to clarify contentious issues on the evolution of the panarthropod head, and lays the foundation from which to further address this complex subject in the future.     

What are the genomic drivers of the rapid evolution of PRDM9?

Mammalian Prdm9 has been proposed to be a key determinant of the positioning of chromosome double-strand breaks during meiosis, a contributor to speciation processes, and the most rapidly evolving gene in human, and other animal, genomes. Prdm9 genes often exhibit substantial variation in their numbers of encoded zinc fingers (ZFs), not only between closely related species but also among individuals of a species. The near-identity of these ZF sequences appears to render them very unstable in copy number. The rare sequence differences, however, cluster within ZF sites that determine the DNA-binding specificity of PRDM9, and these substitutions are frequently positively selected. Here, possible drivers of the rapid evolution of Prdm9 are discussed, including selection for efficient pairing of homologous chromosomes or for recombination of deleterious linked alleles, and selection against depletion of recombination hotspots or against disease-associated genome rearrangement.     

Negative association between parental care and sibling cooperation in earwigs: a new perspective on the early evolution of family life?

The evolution of family life requires net fitness benefits for offspring, which are commonly assumed to mainly derive from parental care. However, an additional source of benefits for offspring is often overlooked: cooperative interactions among juvenile siblings. In this study, we examined how sibling cooperation and parental care could jointly contribute to the early evolution of family life. Specifically, we tested whether the level of food transferred among siblings (sibling cooperation) in the European earwig Forficula auricularia (1) depends on the level of maternal food provisioning (parental care) and (2) is translated into offspring survival, as well as female investment into future reproduction. We show that higher levels of sibling food transfer were associated with lower levels of maternal food provisioning, possibly reflecting a compensatory relationship between sibling cooperation and maternal care. Furthermore, the level of sibling food transfer did not influence offspring survival, but was associated with negative effects on the production of the second and terminal clutch by the tending mothers. These findings indicate that sibling cooperation could mitigate the detrimental effects on offspring survival that result from being tended by low‐quality mothers. More generally, they are in line with the hypothesis that sibling cooperation is an ancestral behaviour that can be retained to compensate for insufficient levels of parental investment.     

Dorso-ventral limb polarity and origin of the ridge: On the fringe of independence?

Molecular and developmental studies of limb pattern formation have recently gained widespread attention. The fact that vertebrate limbs are amenable to both genetic and embryological manipulations has established this model system as a valuable paradigm for studying vertebrate development. Limb buds are polarised along all three major axes and the establishment of the dorso-ventral (DV) polarity is dependent upon cues localised in the trunk, where a DV ectodermal interface is produced by confrontation of dorsal and ventral identities. By analogy to Drosophila imaginal disc development, this interface has been proposed to determine and position an ectodermal organising centre, the Apical Ectodermal Ridge (AER), controlling limb bud outgrowth. Recent fate mapping studies⁽¹⁾ and studies of genes regulating DV limb polarity^(2-6), AER formation^(7,8) and differentiation⁽⁹⁾ suggest, however, that DV patterning and AER induction, though coordinately regulated during limb bud outgrowth, may early on be more dissociated than expected.