Joseph Felsenstein is Professor in the Departments of Genome Sciences and Biology and Adjunct Professor in the Departments of Computer Science and Statistics at the University of Washington in Seattle. He is best known for his work on phylogenetic inference, and is the author of Inferring Phylogenies, and principal author and distributor of the package of phylogenetic inference programs called PHYLIP, and is currently serving as the President of the Society for Molecular Biology & Evolution.

You can reach Joe at

James McInerney is the principle investigator of the Bioinformatics and Molecular Evolution Laboratories at NUI Maynooth. He was one of the founding directors of the Irish Centre for High End Computing, an Associate Editor of Molecular Biology and Evolution, Biology Direct, and Journal of Experimental Zoology, and is currently serving as the Secretary for the Society for Molecular Biology and Evolution.

You can reach James at

Juliette de Meaux is interested in the molecular basis of Darwinian adaptation in natural plant systems. Her works combines the approaches of population, quantitative and molecular genetics to dissect the underpinning of adaptive changes. She completed her PhD at AgroParisTech, under the supervision of Prof. Claire Neema and studied the molecular basis of host-pathogen coevolution in natural populations of common bean. She then spent her Postdoc time in the lab of Prof. Tom Mitchell-Olds at the Max Planck Institute of Chemical Ecology in Jena and worked on the evolution of cis-regulatory DNA. Since 2005, she runs her own lab, first at the Max Planck Institute of Plant Breeding in Cologne and then at the University of Münster. In January 2015, she relocated her lab at the University of Cologne. She is currently serving as the Treasurer for the Society for Molecular Biology and Evolution.

You can reach Juliette at


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The Society for Molecular Biology and Evolution is an international organization whose goals are to provide facilities for association and communication among molecular evolutionists and to further the goals of molecular evolution, as well as its practitioners and teachers. In order to accomplish these goals, the Society publishes two peer-reviewed journals, Molecular Biology and Evolution and Genome Biology and Evolution. The Society sponsors an annual meeting, as well as smaller satellite meetings or workshop on important, focused, and timely topics. It also confers honors and awards to students and researchers.

SMBE 2017

On behalf of the organising committee it is our pleasure to invite you to attend SMBE 2017 - the annual meeting of the Society for Molecular Biology and Evolution. SMBE 2017 will be held from the 2nd-6th of July at the JW Marriott in Austin, TX, USA. The meeting - including plenary talks, symposia presentations, the Walter Fitch symposium, and poster sessions - will showcase the latest research in genomics, population genetics, and molecular biology and evolution. Social activities will include an opening reception, mixers with each poster session, and a conference dinner. We’re looking forward to seeing you in Austin this summer!

More information can be found HERE

Featured News and Updates

SMBE 2017 Abstract Submission Deadline Approaching

We are delighted to announce that the abstract system for the Annual Meeting of the Society for Molecular Biology and Evolution 2017 is open! We are accepting abstracts for talks and posters via the official SMBE 2017 website HEREThe submission deadline is Feb. 1, 2017. Please be aware that registration is not required for abstract submission.

SMBE awards numerous awards for students and postdocs who attend the conference. See the SMBE 2017 meeting awards page HERE or the society awards page HERE for details. All award applications are submitted through the abstract submission system. 

  • Friday, January 13, 2017
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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

Genomic and Transcriptomic Analysis Reveals Spliced Leader Trans-Splicing in Cryptomonads


<span class="paragraphSection">Spliced leader trans-splicing (SLTS) is a poorly understood mechanism that is found in a diversity of eukaryotic lineages. In SLTS, a short RNA sequence is added near the 5′ ends of the transcripts of protein-coding genes by a modified spliceosomal reaction. Available data suggest that SLTS has evolved many times, and might be more likely to evolve in animals. That SLTS might be more likely to evolve in the context of the generally complex transcriptomes characteristic of animals suggests the possibility that SLTS functions in gene regulation or transcriptome diversification, however no general novel function for SLTS is known. Here, I report SLTS in a lineage of cellularly complex unicellular eukaryotes. Cryptomonads are a group of eukaryotic algae that acquired photosynthetic capacity by secondary endosymbiosis of a red alga, and that retain a reduced copy of the nucleus of the engulfed alga. I estimate that at least one-fifth of genes in the model cryptomonad <span style="font-style:italic;">Guillardia theta</span> and its relative <span style="font-style:italic;">Hanusia phi</span> undergo SLTS. I show that hundreds of genes in <span style="font-style:italic;">G. theta</span> generate alternative transcripts by SLTS at alternative sites, however I find little evidence for alternative protein production by alternative SLTS splicing. Interestingly, I find no evidence for substantial operon structure in the <span style="font-style:italic;">G. theta</span> genome, in contrast to previous findings in other lineages with SLTS. These results extend SLTS to another major group of eukaryotes, and heighten the mystery of the evolution of SLTS and its association with cellular and transcriptomic complexity.</span>

Evolutionary Thrift: Mycobacteria Repurpose Plasmid Diversity during Adaptation of Type VII Secretion Systems


<span class="paragraphSection">Mycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS. Plasmid-borne ESX were described recently, and we found evidence that the initial duplication and divergence of ESX systems occurred on plasmids and was driven by selection for advantageous mutations. Plasmid conjugation has been linked to T7SS and type IV secretion systems (T4SS) in mycobacteria, and we discovered that T7SS and T4SS genes evolved in concert on the plasmids. We hypothesize that differentiation of plasmid ESX helps to prevent conjugation among cells harboring incompatible plasmids. Plasmid ESX appear to have been repurposed following migration to the chromosome, and there is evidence of positive selection driving further differentiation of chromosomal ESX. We hypothesize that ESX loci were initially stabilized on the chromosome by mediating their own transfer. These results emphasize the diverse adaptive paths underlying evolution of novelty, which in this case involved plasmid duplications, selection for advantageous mutations in the mobile and core genomes, migration of the loci between plasmids and chromosomes, and lateral transfer among chromosomes. We discuss further implications for the choice of model organism to study ESX functions in <span style="font-style:italic;">Mycobacterium tuberculosis</span>.</span>