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MBE | Most Read

Molecular Biology and Evolution

Jawing Away: Bahama Pupfish Study Identifies Candidate Genes Driving Food-Niches


<span class="paragraphSection">Within the salty lakes of the Bahama’s San Salvador Island is an amazing diversity of fishes that may rival Charles Darwin’s finches in the Galapagos.</span>



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Arctic Inuit, Native American Adaptations to Cold and Body Fat Distribution May Originate from Extinct Ancient Hominid Interbreeding


New Study Provides Research Framework for Tracing Human Migration Events After ‘Out of Africa’ Origins


<span class="paragraphSection">As more DNA sequencing data continues to become available, including extinct hominids, a new human origins study has been performed that augments a trio of influential papers published in 2016 in the journal Nature.</span>

Shell Game: Understanding Gene Patterns Behind Mollusk Diversity


<span class="paragraphSection">From kids walking on the beach to major museums, the amazing diversity of conch shells have captivated the eyes of collectors.</span>

Mathematical Modeling Study Shows Why Present Clinical Antibiotic Management Strategies Do Little to Curb Resistance


<span class="paragraphSection">With an alarming growth in antibiotic resistance and doctors increasingly having to resort to last-chance antibiotics to save patients, is there a better way for hospitals to manage antibiotic treatment regimens?</span>

Deciphering the Routes of invasion of Drosophila suzukii by Means of ABC Random Forest


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Deciphering invasion routes from molecular data is crucial to understanding biological invasions, including identifying bottlenecks in population size and admixture among distinct populations. Here, we unravel the invasion routes of the invasive pest <span style="font-style:italic;">Drosophila suzukii</span> using a multi-locus microsatellite dataset (25 loci on 23 worldwide sampling locations). To do this, we use approximate Bayesian computation (ABC), which has improved the reconstruction of invasion routes, but can be computationally expensive. We use our study to illustrate the use of a new, more efficient, ABC method, ABC random forest (ABC-RF) and compare it to a standard ABC method (ABC-LDA). We find that Japan emerges as the most probable source of the earliest recorded invasion into Hawaii. Southeast China and Hawaii together are the most probable sources of populations in western North America, which then in turn served as sources for those in eastern North America. European populations are genetically more homogeneous than North American populations, and their most probable source is northeast China, with evidence of limited gene flow from the eastern US as well. All introduced populations passed through bottlenecks, and analyses reveal five distinct admixture events. These findings can inform hypotheses concerning how this species evolved between different and independent source and invasive populations. Methodological comparisons indicate that ABC-RF and ABC-LDA show concordant results if ABC-LDA is based on a large number of simulated datasets but that ABC-RF out-performs ABC-LDA when using a comparable and more manageable number of simulated datasets, especially when analyzing complex introduction scenarios.</span>

Evolution of Rosaceae Fruit Types Based on Nuclear Phylogeny in the Context of Geological Times and Genome Duplication


<span class="paragraphSection"><span style="font-style:italic;">Yezi Xiang, Chien-Hsun Huang, Yi Hu, Jun Wen, Shisheng Li, Tingshuang Yi, Hongyi Chen, Jun Xiang, and Hong Ma</span></span>

Evolution of DNA Methylation across Insects


<span class="paragraphSection">Adam J. Bewick, Kevin J. Vogel, Allen J. Moore, and Robert J. Schmitz</span>

Corrigendum Correction to “Novel hydrogenosomes in the microaerophilic jakobid Stygiella incarcerata ”


<span class="paragraphSection">Mol. Biol. Evol. 33(9):2318–2336. doi: <strong><a href="article.aspx?volume=&page=">10.1093/molbev/msw103<span></span></a></strong></span>

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as “antibiotic cycling” and “antibiotic mixing.” However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to “cycle” between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic.<strong><span style="font-style:italic;">Key words</span></strong>: antibiotic cycling, antibiotic mixing, optimal control, stochastic models.</span>

A Working Model of the Deep Relationships of Diverse Modern Human Genetic Lineages Outside of Africa


<span class="paragraphSection"><div class="boxTitle">Abstract</div>A major topic of interest in human prehistory is how the large-scale genetic structure of modern populations outside of Africa was established. Demographic models have been developed that capture the relationships among small numbers of populations or within particular geographical regions, but constructing a phylogenetic tree with gene flow events for a wide diversity of non-Africans remains a difficult problem. Here, we report a model that provides a good statistical fit to allele-frequency correlation patterns among East Asians, Australasians, Native Americans, and ancient western and northern Eurasians, together with archaic human groups. The model features a primary eastern/western bifurcation dating to at least 45,000 years ago, with Australasians nested inside the eastern clade, and a parsimonious set of admixture events. While our results still represent a simplified picture, they provide a useful summary of deep Eurasian population history that can serve as a null model for future studies and a baseline for further discoveries.</span>

Oncogenes without a Neighboring Tumor-Suppressor Gene Are More Prone to Amplification


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Focal copy number gains or losses are important genomic hallmarks of cancer. The genomic distribution of oncogenes and tumor-suppressor genes (TSG) in relation to focal copy number aberrations is unclear. Our analysis revealed that the mean distance of TSGs from oncogenes was significantly shorter than that of noncancer genes, suggesting that oncogenes and TSGs tend to be in close physical proximity in the human genome. Such relationship was conserved in mouse and drosophila. Pan-cancer analysis using data from The Cancer Genome Atlas indicated that oncogenes without a nearby TSG are more prone to amplification. In conclusion, our study provides evidence for the nonrandom distribution of oncogenes and TSGs across different species. Our data also support that the existence of a neighboring TSG can suppress amplification of an oncogene, shedding new light on a previously unappreciated protective mechanism of TSGs.</span>

Deleterious Variants in Asian Rice and the Potential Cost of Domestication


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Many SNPs are predicted to encode deleterious amino acid variants. These slightly deleterious mutations can provide unique insights into population history, the dynamics of selection, and the genetic bases of phenotypes. This is especially true for domesticated species, where a history of bottlenecks and selection may affect the frequency of deleterious variants and signal a “cost of domestication”. Here, we investigated the numbers and frequencies of deleterious variants in Asian rice (<span style="font-style:italic;">Oryza sativa</span>), focusing on two varieties (<span style="font-style:italic;">japonica</span> and <span style="font-style:italic;">indica</span>) and their wild relative (<span style="font-style:italic;">O. rufipogon</span>). We investigated three signals of a potential cost of domestication in Asian rice relative to <span style="font-style:italic;">O. rufipogon</span>: an increase in the frequency of deleterious SNPs (dSNPs), an enrichment of dSNPs compared with synonymous SNPs (sSNPs), and an increased number of deleterious variants. We found evidence for all three signals, and domesticated individuals contained ∼3–4% more deleterious alleles than wild individuals. Deleterious variants were enriched within low recombination regions of the genome and experienced frequency increases similar to sSNPs within regions of putative selective sweeps. A characteristic feature of rice domestication was a shift in mating system from outcrossing to predominantly selfing. Forward simulations suggest that this shift in mating system may have been the dominant factor in shaping both deleterious and neutral diversity in rice.</span>

Seed Plant-Specific Gene Lineages Involved in Carpel Development


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Evolutionary innovations are important drivers of speciation and some are the defining characters of entire phyla. One such major innovation is the carpel, the unifying character and most complex plant organ, composed of many clearly distinct tissue types to ensure reproductive success. The origin of the carpel is unknown, but many components of the gene regulatory network (GRN) governing carpel development and their genetic interactions are known from the core eudicot <span style="font-style:italic;">Arabidopsis thaliana</span>. To unravel the evolution of the carpel GRN and to discriminate between “early” and “late” steps in carpel evolution, we calculated thorough phylogeny reconstructions based on sequenced genomes. The <span style="font-style:italic;">A. thaliana</span> carpel GRN members <span style="font-style:italic;">ALCATRAZ</span> (<span style="font-style:italic;">ALC</span>), <span style="font-style:italic;">CRABS CLAW</span> (CRC), <span style="font-style:italic;">HALF FILLED</span> (<span style="font-style:italic;">HAF</span>), <span style="font-style:italic;">HECATE</span> (<span style="font-style:italic;">HEC</span>), <span style="font-style:italic;">INDEHISCENT</span> (<span style="font-style:italic;">IND</span>), <span style="font-style:italic;">NGATHA</span> (<span style="font-style:italic;">NGA</span>), and <span style="font-style:italic;">SPATULA</span> (<span style="font-style:italic;">SPT</span>) were analyzed in their phylogenetic context. We find that the carpel GRN components are of various ages, but interestingly, we identify especially high retention rates for carpel development genes in Brassicaceae. Our data suggest that genes whose <span style="font-style:italic;">A. thaliana</span> homologs are involved in processes already present in the most recent common ancestor of seed plants, such as reproductive meristem termination or adaxial/abaxial polarity specification, are not retained in duplicates after whole genome duplications (WGD). In contrast, genes involved in processes associated with derived carpel characters in <span style="font-style:italic;">Arabidopsis</span>, such as the transmitting tract or style development show a higher gene retention rate after WGD. This work provides a starting point for analyses of carpel genes in early diverging angiosperms which would be very informative for evolutionary studies.</span>

The Origin of Mitochondrial Cristae from Alphaproteobacteria


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Mitochondria are the respiratory organelles of eukaryotes and their evolutionary history is deeply intertwined with that of eukaryotes. The compartmentalization of respiration in mitochondria occurs within cristae, whose evolutionary origin has remained unclear. Recent discoveries, however, have revived the old notion that mitochondrial cristae could have had a pre-endosymbiotic origin. Mitochondrial cristae are likely homologous to the intracytoplasmic membranes (ICMs) used by diverse alphaproteobacteria for harnessing energy. Because the Mitochondrial Contact site and Cristae Organizing System (MICOS) that controls the development of cristae evolved from a simplified version that is phylogenetically restricted to Alphaproteobacteria (alphaMICOS), ICMs most probably transformed into cristae during the endosymbiotic origin of mitochondria. This inference is supported by the sequence and structural similarities between MICOS and alphaMICOS, and the expression pattern and cellular localization of alphaMICOS. Given that cristae and ICMs develop similarly, alphaMICOS likely functions analogously to mitochondrial MICOS by culminating ICM development with the creation of tubular connections and membrane contact sites at the alphaproteobacterial envelope. Mitochondria thus inherited a pre-existing ultrastructure adapted to efficient energy transduction from their alphaproteobacterial ancestors. The widespread nature of purple bacteria among alphaproteobacteria raises the possibility that cristae evolved from photosynthetic ICMs.</span>

Genome Sequencing Reveals the Origin of the Allotetraploid Arabidopsis suecica


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Polyploidy is an example of instantaneous speciation when it involves the formation of a new cytotype that is incompatible with the parental species. Because new polyploid individuals are likely to be rare, establishment of a new species is unlikely unless polyploids are able to reproduce through self-fertilization (selfing), or asexually. Conversely, selfing (or asexuality) makes it possible for polyploid species to originate from a single individual—a <span style="font-style:italic;">bona fide</span> speciation event. The extent to which this happens is not known. Here, we consider the origin of <span style="font-style:italic;">Arabidopsis suecica</span>, a selfing allopolyploid between <span style="font-style:italic;">Arabidopsis thaliana</span> and <span style="font-style:italic;">Arabidopsis arenosa</span>, which has hitherto been considered to be an example of a unique origin. Based on whole-genome re-sequencing of 15 natural <span style="font-style:italic;">A. suecica</span> accessions, we identify ubiquitous shared polymorphism with the parental species, and hence conclusively reject a unique origin in favor of multiple founding individuals. We further estimate that the species originated after the last glacial maximum in Eastern Europe or central Eurasia (rather than Sweden, as the name might suggest). Finally, annotation of the self-incompatibility loci in <span style="font-style:italic;">A. suecica</span> revealed that both loci carry non-functional alleles. The locus inherited from the selfing <span style="font-style:italic;">A. thaliana</span> is fixed for an ancestral non-functional allele, whereas the locus inherited from the outcrossing <span style="font-style:italic;">A. arenosa</span> is fixed for a novel loss-of-function allele. Furthermore, the allele inherited from <span style="font-style:italic;">A. thaliana</span> is predicted to transcriptionally silence the allele inherited from <span style="font-style:italic;">A. arenosa</span>, suggesting that loss of self-incompatibility may have been instantaneous. </span>

The Rice Paradox: Multiple Origins but Single Domestication in Asian Rice


<span class="paragraphSection"><div class="boxTitle">Abstract</div>The origin of domesticated Asian rice (<span style="font-style:italic;">Oryza sativa</span>) has been a contentious topic, with conflicting evidence for either single or multiple domestication of this key crop species. We examined the evolutionary history of domesticated rice by analyzing de novo assembled genomes from domesticated rice and its wild progenitors. Our results indicate multiple origins, where each domesticated rice subpopulation (<span style="font-style:italic;">japonica</span>, <span style="font-style:italic;">indica</span>, and <span style="font-style:italic;">aus</span>) arose separately from progenitor <span style="font-style:italic;">O. rufipogon</span> and/or <span style="font-style:italic;">O. nivara</span>. Coalescence-based modeling of demographic parameters estimate that the first domesticated rice population to split off from <span style="font-style:italic;">O. rufipogon</span> was <span style="font-style:italic;">O. sativa</span> ssp. <span style="font-style:italic;">japonica</span>, occurring at ∼13.1–24.1 ka, which is an order of magnitude older then the earliest archeological date of domestication. This date is consistent, however, with the expansion of <span style="font-style:italic;">O. rufipogon</span> populations after the Last Glacial Maximum ∼18 ka and archeological evidence for early wild rice management in China. We also show that there is significant gene flow from <span style="font-style:italic;">japonica</span> to both <span style="font-style:italic;">indica</span> (∼17%) and <span style="font-style:italic;">aus</span> (∼15%), which led to the transfer of domestication alleles from early-domesticated <span style="font-style:italic;">japonica</span> to proto-<span style="font-style:italic;">indica</span> and proto-<span style="font-style:italic;">aus</span> populations. Our results provide support for a model in which different rice subspecies had separate origins, but that de novo domestication occurred only once, in <span style="font-style:italic;">O. sativa</span> ssp. <span style="font-style:italic;">japonica</span>, and introgressive hybridization from early <span style="font-style:italic;">japonica</span> to proto-<span style="font-style:italic;">indica</span> and proto-<span style="font-style:italic;">aus</span> led to domesticated <span style="font-style:italic;">indica</span> and <span style="font-style:italic;">aus</span> rice.</span>

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity


<span class="paragraphSection"><div class="boxTitle">Abstract</div>Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four <span style="font-style:italic;">Pinctada</span> (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium.</span>

miRNAs in Ancient Tissue Specimens of the Tyrolean Iceman


<span class="paragraphSection"><div class="boxTitle">Abstract</div>The analysis of nucleic acids in ancient samples is largely limited to DNA. Small noncoding RNAs (microRNAs) are known to be evolutionary conserved and stable. To gain knowledge on miRNAs measured from ancient samples, we profiled microRNAs in cryoconserved mummies. First, we established the approach on a World War One warrior, the “Kaiserjäger”, which has been preserved for almost one century. Then, we profiled seven ancient tissue specimens including skeletal muscle, stomach mucosa, stomach content and two corpus organ tissues of the 5,300-year-old copper age mummy Iceman and compared these profiles to the presence of organ-specific miRNAs in modern tissues. Our analyses suggest the presence of specific miRNAs in the different Iceman’s tissues. Of 1,066 analyzed human miRNAs, 31 were discovered across all biopsies and 87 miRNAs were detected only in a single sample. To check for potential microbiological contaminations, all miRNAs detected in Iceman samples and not present in ancient samples were mapped to 14,582 bacterial and viral genomes. We detected few hits (3.9% of miRNAs compared with 3.6% of miRNAs). Interestingly, the miRNAs with higher abundance across all ancient tissues were significantly enriched for Guanine (<span style="font-style:italic;">P</span> value of 10–13) and Cytosine (<span style="font-style:italic;">P</span> value of 10–7). The same pattern was observed for modern tissues. Comparing miRNAs measured from ancient organs to modern tissue patterns highlighted significant similarities, e.g., for miRNAs present in the muscle. Our first comprehensive analysis of microRNAs in ancient human tissues indicates that these stable molecules can be detected in tissue specimens after 5,300 years.</span>

GBE | Most Read

Genome Biology & Evolution

RNA Editing During Sexual Development Occurs in Distantly Related Filamentous Ascomycetes


<span class="paragraphSection">RNA editing is a post-transcriptional process that modifies RNA molecules leading to transcript sequences that differ from their template DNA. A-to-I editing was found to be widely distributed in nuclear transcripts of metazoa, but was detected in fungi only recently in a study of the filamentous ascomycete <span style="font-style:italic;">Fusarium graminearum</span> that revealed extensive A-to-I editing of mRNAs in sexual structures (fruiting bodies). Here, we searched for putative RNA editing events in RNA-seq data from <span style="font-style:italic;">Sordaria macrospora</span> and <span style="font-style:italic;">Pyronema confluens</span>, two distantly related filamentous ascomycetes, and in data from the Taphrinomycete <span style="font-style:italic;">Schizosaccharomyces pombe</span>. Like <span style="font-style:italic;">F. graminearum</span>, <span style="font-style:italic;">S. macrospora</span> is a member of the Sordariomycetes, whereas <span style="font-style:italic;">P. confluens</span> belongs to the early-diverging group of Pezizomycetes. We found extensive A-to-I editing in RNA-seq data from sexual mycelium from both filamentous ascomycetes, but not in vegetative structures. A-to-I editing was not detected in different stages of meiosis of <span style="font-style:italic;">S. pombe</span>. A comparison of A-to-I editing in <span style="font-style:italic;">S. macrospora</span> with <span style="font-style:italic;">F. graminearum</span> and <span style="font-style:italic;">P. confluens</span>, respectively, revealed little conservation of individual editing sites. An analysis of RNA-seq data from two sterile developmental mutants of <span style="font-style:italic;">S. macrospora</span> showed that A-to-I editing is strongly reduced in these strains. Sequencing of cDNA fragments containing more than one editing site from <span style="font-style:italic;">P. confluens</span> showed that at the beginning of sexual development, transcripts were incompletely edited or unedited, whereas in later stages transcripts were more extensively edited. Taken together, these data suggest that A-to-I RNA editing is an evolutionary conserved feature during fruiting body development in filamentous ascomycetes.</span>

Recombination-Mediated Host Adaptation by Avian Staphylococcus aureus


<span class="paragraphSection"><span style="font-style:italic;">Staphylococcus aureus</span> are globally disseminated among farmed chickens causing skeletal muscle infections, dermatitis, and septicaemia. The emergence of poultry-associated lineages has involved zoonotic transmission from humans to chickens but questions remain about the specific adaptations that promote proliferation of chicken pathogens. We characterized genetic variation in a population of genome-sequenced <span style="font-style:italic;">S. aureus</span> isolates of poultry and human origin. Genealogical analysis identified a dominant poultry-associated sequence cluster within the CC5 clonal complex. Poultry and human CC5 isolates were significantly distinct from each other and more recombination events were detected in the poultry isolates. We identified 44 recombination events in 33 genes along the branch extending to the poultry-specific CC5 cluster, and 47 genes were found more often in CC5 poultry isolates compared with those from humans. Many of these gene sequences were common in chicken isolates from other clonal complexes suggesting horizontal gene transfer among poultry associated lineages. Consistent with functional predictions for putative poultry-associated genes, poultry isolates showed enhanced growth at 42 °C and greater erythrocyte lysis on chicken blood agar in comparison with human isolates. By combining phenotype information with evolutionary analyses of staphylococcal genomes, we provide evidence of adaptation, following a human-to-poultry host transition. This has important implications for the emergence and dissemination of new pathogenic clones associated with modern agriculture.</span>

A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages


<span class="paragraphSection"><span style="font-style:italic;">Mycobacterium tuberculosis</span> is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an <span style="font-style:italic;">M. tuberculosis</span> classification approach based on functional polymorphisms in virulence genes. An <span style="font-style:italic;">M. tuberculosis</span> virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin–antitoxin systems. Another catalog of 1,573 <span style="font-style:italic;">M. tuberculosis</span> isolates of different lineages has been developed. The developed SNP-calling program has identified 3,563 nonsynonymous SNPs. The constructed SNP-based phylogeny reflected the evolutionary relationship between lineages and detected new sublineages. SNP analysis of sublineage F15/LAM4/KZN revealed four lineage-specific mutations in <span style="font-style:italic;">cyp125, mce3B, vapC25</span>, and <span style="font-style:italic;">vapB34</span>. The Ural lineage has been divided into two geographical clusters based on different SNPs in virulence genes. A new sublineage, B0/N-90, was detected inside the Beijing-B0/W-148 by SNPs in <span style="font-style:italic;">irtB, mce3F</span> and <span style="font-style:italic;">vapC46</span>. We have found 27 members of B0/N-90 among the 227 available genomes of the Beijing-B0/W-148 sublineage. Whole-genome sequencing of strain B9741, isolated from an HIV-positive patient, was demonstrated to belong to the new B0/N-90 group. A primer set for PCR detection of B0/N-90 lineage-specific mutations has been developed. The prospective use of <span style="font-style:italic;">mce3</span> mutant genes as genetically engineered vaccine is discussed.</span>

Evolutionary Dynamics of Regulatory Changes Underlying Gene Expression Divergence among Saccharomyces Species


<span class="paragraphSection">Heritable changes in gene expression are important contributors to phenotypic differences within and between species and are caused by mutations in <span style="font-style:italic;">cis-</span>regulatory elements and <span style="font-style:italic;">trans</span>-regulatory factors. Although previous work has suggested that <span style="font-style:italic;">cis</span>-regulatory differences preferentially accumulate with time, technical restrictions to closely related species and limited comparisons have made this observation difficult to test. To address this problem, we used allele-specific RNA-seq data from <span style="font-style:italic;">Saccharomyces</span> species and hybrids to expand both the evolutionary timescale and number of species in which the evolution of regulatory divergence has been investigated. We find that as sequence divergence increases, <span style="font-style:italic;">cis</span>-regulatory differences do indeed become the dominant type of regulatory difference between species, ultimately becoming a better predictor of expression divergence than <span style="font-style:italic;">trans</span>-regulatory divergence. When both <span style="font-style:italic;">cis</span>- and <span style="font-style:italic;">trans</span>-regulatory differences accumulate for the same gene, they more often have effects in opposite directions than in the same direction, indicating widespread compensatory changes underlying the evolution of gene expression. The frequency of compensatory changes within and between species and the magnitude of effect for the underlying <span style="font-style:italic;">cis-</span> and <span style="font-style:italic;">trans</span>-regulatory differences suggests that compensatory changes accumulate primarily due to selection against divergence in gene expression as a result of weak stabilizing selection on gene expression levels. These results show that <span style="font-style:italic;">cis</span>-regulatory differences and compensatory changes in regulation play increasingly important roles in the evolution of gene expression as time increases.</span>

Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins


<span class="paragraphSection">RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family <span style="font-style:italic;">Flaviviridae</span>) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5′ terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins.</span>

Phylogenetics of Lophotrochozoan bHLH Genes and the Evolution of Lineage-Specific Gene Duplicates


<span class="paragraphSection">The gain and loss of genes encoding transcription factors is of importance to understanding the evolution of gene regulatory complexity. The basic helix–loop–helix (bHLH) genes encode a large superfamily of transcription factors. We systematically classify the bHLH genes from five mollusc, two annelid and one brachiopod genomes, tracing the pattern of bHLH gene evolution across these poorly studied Phyla. In total, 56–88 bHLH genes were identified in each genome, with most identifiable as members of previously described bilaterian families, or of new families we define. Of such families only one, <span style="font-style:italic;">Mesp</span>, appears lost by all these species. Additional duplications have also played a role in the evolution of the bHLH gene repertoire, with many new lophotrochozoan-, mollusc-, bivalve-, or gastropod-specific genes defined. Using a combination of transcriptome mining, RT-PCR, and in situ hybridization we compared the expression of several of these novel genes in tissues and embryos of the molluscs <span style="font-style:italic;">Crassostrea gigas</span> and <span style="font-style:italic;">Patella vulgata</span>, finding both conserved expression and evidence for neofunctionalization. We also map the positions of the genes across these genomes, identifying numerous gene linkages. Some reflect recent paralog divergence by tandem duplication, others are remnants of ancient tandem duplications dating to the lophotrochozoan or bilaterian common ancestors. These data are built into a model of the evolution of bHLH genes in molluscs, showing formidable evolutionary stasis at the family level but considerable within-family diversification by tandem gene duplication.</span>