Untangling the Evolution of the Receptor-Binding Motif of SARS-CoV-2.

The spike protein determines the host-range specificity of coronaviruses. In particular, the Receptor-Binding Motif in the spike protein from SARS-CoV-2 contains the amino acids involved in molecular recognition of the host Angiotensin Converting Enzyme 2. Therefore, to understand how SARS-CoV-2 acquired its capacity to infect humans it is necessary to reconstruct the evolution of this important motif. Early during the pandemic, it was proposed that the SARS-CoV-2 Receptor-Binding Domain was acquired via recombination with a pangolin infecting coronavirus. This proposal was challenged by an alternative explanation that suggested that the Receptor-Binding Domain from SARS-CoV-2 did not originated via recombination with a coronavirus from a pangolin. Instead, this alternative hypothesis proposed that the Receptor-Binding Motif from the bat coronavirus RaTG13, was acquired via recombination with an unidentified coronavirus. And as a consequence of this event, the Receptor-Binding Domain from the pangolin coronavirus appeared as phylogenetically closer to SARS-CoV-2. Recently, the genomes from coronaviruses from Cambodia (bat_RShST182/200) and Laos (BANAL-20-52/103/247) which are closely related to SARS-CoV-2 were reported. However, no detailed analysis of the evolution of the Receptor-Binding Motif from these coronaviruses was reported. Here we revisit the evolution of the Receptor-Binding Domain and Motif in the light of the novel coronavirus genome sequences. Specifically, we wanted to test whether the above coronaviruses from Cambodia and Laos were the source of the Receptor-Binding Domain from RaTG13. We found that the Receptor-Binding Motif from these coronaviruses is phylogenetically closer to SARS-CoV-2 than to RaTG13. Therefore, the source of the Receptor-Binding Domain from RaTG13 is still unidentified. In accordance with previous studies, our results are consistent with the hypothesis that the Receptor-Binding Motif from SARS-CoV-2 evolved by vertical inheritance from a bat-infecting population of coronaviruses.

Yeast diversity in open agave fermentations across Mexico.

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX-1.0 culture collection by isolating 4524 strains from 68 sites with diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and validated a subset of the strains by ITS and D1/D2 sequencing, which also revealed two potential novel species of Saccharomycetales. Overall, the composition of yeast communities was weakly associated with local variables and types of climate, yet a core set of six species was consistently isolated from most producing regions. To explore the intraspecific variation of the yeasts from agave fermentations, we sequenced the genomes of four isolates of the nonconventional yeast Kazachstania humilis. The genomes of these four strains were substantially distinct from a European isolate of the same species, suggesting that they may belong to different populations. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.

Translation Comes First: Ancient and Convergent Selection of Codon Usage Bias Across Prokaryotic Genomes.

Codon usage is the outcome of different evolutionary processes and can inform us about the conditions in which organisms live and evolve. Here, we present R_ENC', which is an improvement to the original S index developed by dos Reis et al. (2004). Our index is less sensitive to G+C content, which greatly affects synonymous codon usage in prokaryotes, making it better suited to detect selection acting on codon usage. We used R_ENC' to estimate the extent of selected codon usage bias in 1800 genomes representing 26 prokaryotic phyla. We found that Gammaproteobacteria, Betaproteobacteria, Actinobacteria, and Firmicutes are the phyla/subphyla showing more genomes with selected codon usage bias. In particular, we found that several lineages within Gammaproteobacteria and Firmicutes show a similar set of functional terms enriched in genes under selected codon usage bias, indicating convergent evolution. We also show that selected codon usage bias tends to evolve in genes coding for the translation machinery before other functional GO terms. Finally, we discuss the possibility to use R_ENC' to predict whether lineages evolved in copiotrophic or oligotrophic environments.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Transcriptome analysis of bolting in A. tequilana reveals roles for florigen, MADS, fructans and gibberellins.

BACKGROUND: Reliable indicators for the onset of flowering are not available for most perennial monocarpic species, representing a drawback for crops such as bamboo, agave and banana. The ability to predict and control the transition to the reproductive stage in A. tequilana would represent an advantage for field management of agaves for tequila production and for the development of a laboratory model for agave species. RESULTS: Consistent morphological features could not be determined for the vegetative to reproductive transition in A. tequilana. However, changes in carbohydrate metabolism where sucrose decreased and fructans of higher degree of polymerization increased in leaves before and after the vegetative to reproductive transition were observed. At the molecular level, transcriptome analysis from leaf and shoot apical meristem tissue of A. tequilana plants from different developmental stages identified OASES as the most effective assembly program and revealed evidence for incomplete transcript processing in the highly redundant assembly obtained. Gene ontology analysis uncovered enrichment for terms associated with carbohydrate and hormone metabolism and detailed analysis of expression patterns for individual genes revealed roles for specific Flowering locus T (florigen), MADS box proteins, gibberellins and fructans in the transition to flowering. CONCLUSIONS: Based on the data obtained, a preliminary model was developed to describe the regulatory mechanisms underlying the initiation of flowering in A. tequilana. Identification of specific promoter and repressor Flowering Locus T and MADS box genes facilitates functional analysis and the development of strategies to modulate the vegetative to reproductive transition in A. tequilana.

Increased rates of protein evolution and asymmetric deceleration after the whole-genome duplication in yeasts.

BACKGROUND: Whole-genome duplication (WGD) events have shaped the genomes of eukaryotic organisms. Relaxed selection after duplication along with inherent functional constraints are thought to determine the fate of the paralogs and, ultimately, the evolution of gene function. Here, we investigated the rate of protein evolution (as measured by dN/dS ratios) before and after the WGD in the hemiascomycete yeasts, and the way in which changes in such rates relate to molecular and biological function. RESULTS: For most groups of orthologous genes (81%) we observed a change in the rates of evolution after genome duplication. Genes with atypically-low dN/dS ratio before the WGD were prone to increase their rates of evolution after duplication. Importantly, the paralogs were often different in their rates of evolution after the WGD (50% cases), however, this was more consistent with an asymmetric deceleration in the protein-evolution rates, rather than an asymmetric increase of the initial rates. Functional-category analysis showed that regulatory proteins such as protein kinases and transcription factors were enriched in genes that increase their rates of evolution after the WGD. While changes in the rate of protein-sequence evolution were associated to protein abundance, content of disordered regions, and contribution to fitness, these features were an attribute of specific functional classes. CONCLUSIONS: Our results indicate that strong purifying selection in ancestral pre-duplication sequences is a strong predictor of increased rates after the duplication in yeasts and that asymmetry in evolution rate is established during the deceleration phase. In addition, changes in the rates at which paralogous sequences evolve before and after WGD are different for specific protein functions; increased rates of protein evolution after duplication occur preferentially in specific protein functions.

Natural selection drove metabolic specialization of the chromatophore in Paulinella chromatophora.

BACKGROUND: Genome degradation of host-restricted mutualistic endosymbionts has been attributed to inactivating mutations and genetic drift while genes coding for host-relevant functions are conserved by purifying selection. Unlike their free-living relatives, the metabolism of mutualistic endosymbionts and endosymbiont-originated organelles is specialized in the production of metabolites which are released to the host. This specialization suggests that natural selection crafted these metabolic adaptations. In this work, we analyzed the evolution of the metabolism of the chromatophore of Paulinella chromatophora by in silico modeling. We asked whether genome reduction is driven by metabolic engineering strategies resulted from the interaction with the host. As its widely known, the loss of enzyme coding genes leads to metabolic network restructuring sometimes improving the production rates. In this case, the production rate of reduced-carbon in the metabolism of the chromatophore. RESULTS: We reconstructed the metabolic networks of the chromatophore of P. chromatophora CCAC 0185 and a close free-living relative, the cyanobacterium Synechococcus sp. WH 5701. We found that the evolution of free-living to host-restricted lifestyle rendered a fragile metabolic network where >80% of genes in the chromatophore are essential for metabolic functionality. Despite the lack of experimental information, the metabolic reconstruction of the chromatophore suggests that the host provides several metabolites to the endosymbiont. By using these metabolites as intracellular conditions, in silico simulations of genome evolution by gene lose recover with 77% accuracy the actual metabolic gene content of the chromatophore. Also, the metabolic model of the chromatophore allowed us to predict by flux balance analysis a maximum rate of reduced-carbon released by the endosymbiont to the host. By inspecting the central metabolism of the chromatophore and the free-living cyanobacteria we found that by improvements in the gluconeogenic pathway the metabolism of the endosymbiont uses more efficiently the carbon source for reduced-carbon production. In addition, our in silico simulations of the evolutionary process leading to the reduced metabolic network of the chromatophore showed that the predicted rate of released reduced-carbon is obtained in less than 5% of the times under a process guided by random gene deletion and genetic drift. We interpret previous findings as evidence that natural selection at holobiont level shaped the rate at which reduced-carbon is exported to the host. Finally, our model also predicts that the ABC phosphate transporter (pstSACB) which is conserved in the genome of the chromatophore of P. chromatophora strain CCAC 0185 is a necessary component to release reduced-carbon molecules to the host. CONCLUSION: Our evolutionary analysis suggests that in the case of Paulinella chromatophora natural selection at the holobiont level played a prominent role in shaping the metabolic specialization of the chromatophore. We propose that natural selection acted as a "metabolic engineer" by favoring metabolic restructurings that led to an increased release of reduced-carbon to the host.

Identification of effector-like proteins in Trichoderma spp. and role of a hydrophobin in the plant-fungus interaction and mycoparasitism.

BACKGROUND: Trichoderma spp. can establish beneficial interactions with plants by promoting plant growth and defense systems, as well as, antagonizing fungal phytopathogens in mycoparasitic interactions. Such interactions depend on signal exchange between both participants and can be mediated by effector proteins that alter the host cell structure and function, allowing the establishment of the relationship. The main purpose of this work was to identify, using computational methods, candidates of effector proteins from T. virens, T. atroviride and T. reesei, validate the expression of some of the genes during a beneficial interaction and mycoparasitism and to define the biological function for one of them. RESULTS: We defined a catalogue of putative effector proteins from T. virens, T. atroviride and T. reesei. We further validated the expression of 16 genes encoding putative effector proteins from T. virens and T. atroviride during the interaction with the plant Arabidopsis thaliana, and with two anastomosis groups of the phytopathogenic fungus Rhizoctonia solani. We found genes which transcript levels are modified in response to the presence of both plant fungi, as well as genes that respond only to either a plant or a fungal host. Further, we show that overexpression of the gene tvhydii1, a Class II hydrophobin family member, enhances the antagonistic activity of T. virens against R. solani AG2. Further, deletion of tvhydii1 results in reduced colonization of plant roots, while its overexpression increases it. CONCLUSIONS: Our results show that Trichoderma is able to respond in different ways to the presence of a plant or a fungal host, and it can even distinguish between different strains of fungi of a given species. The putative effector proteins identified here may play roles in preventing perception of the fungus by its hosts, favoring host colonization or protecting it from the host's defense response. Finally, the novel effector protein TVHYDII1 plays a role in plant root colonization by T, virens, and participates in its antagonistic activity against R. solani.

Identification of Xenologs and Their Characteristic Low Expression Levels in the Cyanobacterium Synechococcus elongatus.

Horizontal gene transfer (HGT) is a central process in prokaryotic evolution. Once a gene is introduced into a genome by HGT, its contribution to the fitness of the recipient cell depends in part on its expression level. Here we show that in Synechococcus elongatus PCC 7942, xenologs derived from non-cyanobacterial sources exhibited lower expression levels than native genes in the genome. In accord with our observation, xenolog codon adaptation indexes also displayed relatively low expression values. These results are in agreement with previous reports that suggested the relative neutrality of most xenologs. However, we also demonstrated that some of the xenologs detected participated in cellular functions, including iron starvation acclimation and nitrate reduction, which corroborate the role of HGT in bacterial adaptation. For example, the expression levels of some of the xenologs detected are known to increase under iron-limiting conditions. We interpreted the overall pattern as an indication that there is a selection pressure against high expression levels of xenologs. However, when a xenolog protein product confers a selective advantage, natural selection can further modulate its expression level to meet the requirements of the recipient cell. In addition, we show that ORFans did not exhibit significantly lower expression levels than native genes in the genome, which suggested an origin other than xenology.

Plasmid conjugation from proteobacteria as evidence for the origin of xenologous genes in cyanobacteria.

Comparative genomics have shown that 5% of Synechococcus elongatus PCC 7942 genes are of probable proteobacterial origin. To investigate the role of interphylum conjugation in cyanobacterial gene acquisition, we tested the ability of a set of prototype proteobacterial conjugative plasmids (RP4, pKM101, R388, R64, and F) to transfer DNA from Escherichia coli to S. elongatus. A series of BioBrick-compatible, mobilizable shuttle vectors was developed. These vectors were based on the putative origin of replication of the Synechococcus resident plasmid pANL. Not only broad-host-range plasmids, such as RP4 and R388, but also narrower-host-range plasmids, such as pKM101, all encoding MPFT-type IV secretion systems, were able to transfer plasmid DNA from E. coli to S. elongatus by conjugation. Neither MPFF nor MPFI could be used as interphylum DNA delivery agents. Reciprocally, pANL-derived cointegrates could be introduced in E. coli by electroporation, where they conferred a functional phenotype. These results suggest the existence of potentially ample channels of gene flow between proteobacteria and cyanobacteria and point to MPFT-based interphylum conjugation as a potential mechanism to explain the proteobacterial origin of a majority of S. elongatus xenologous genes.

Low complexity regions (LCRs) contribute to the hypervariability of the HIV-1 gp120 protein.

Low complexity regions (LCRs) are sequences of nucleic acids or proteins defined by a compositional bias. Their occurrence has been confirmed in sequences of the three cellular lineages (Bacteria, Archaea and Eucarya), and has also been reported in viral genomes. We present here the results of a detailed computer analysis of the LCRs present in the HIV-1 glycoprotein 120 (gp120) encoded by the viral gene env. The analysis was performed using a sample of 3637 Env polyprotein sequences derived from 4117 completely sequenced and translated HIV-1 genomes available in public databases as of December 2012. We have identified 1229 LCRs located in four different regions of the gp120 protein that correspond to four of the five regions that have been identified as hypervariable (V1, V2, V4 and V5). The remaining 29 LCRs are found in the signal peptide and in the conserved regions C2, C3, C4 and C5. No LCR has been identified in the hypervariable region V3. The LCRs detected in the V1, V2, V4, and V5 hypervariable regions exhibit a high Asn content in their amino acid composition, which very likely correspond to glycosylation sites, which may contribute to the retroviral ability to avoid the immune system. In sharp contrast with what is observed in gp120 proteins lacking LCRs, the glycosylation sites present in LCRs tend to be clustered towards the center of the region forming well-defined islands. The results presented here suggest that LCRs represent a hitherto undescribed source of genomic variability in lentivirus, and that these repeats may represent an important source of antigenic variation in HIV-1 populations. The results reported here may exemplify the evolutionary processes that may have increased the size of primitive cellular RNA genomes and the role of LCRs as a source of raw material during the processes of evolutionary acquisition of new functions.

CurSa: scripts to curate metadata and sample genomes from GISAID for analysis and display in nextstrain and microreact.

The coronavirus SARS-CoV-2 is the most sequenced pathogen ever, with several million genome copies deposited in the GISAID database. This large amount of genomic information poses non-trivial bioinformatic challenges for those interested in studying the evolution of SARS-CoV-2. One common problem when studying the phylogeny of the coronavirus in its geographical context is to count with accurate information of the location of the samples. However, this information is filled by hand by research groups all over the world and sometimes typos and inconsistencies are introduced in the metadata when submitting the sequences to GISAID. Correcting these errors is laborious and time-consuming. Here, we provide a suite of Perl scripts designated to facilitate the curation of this vital information and perform a random sampling of genome sequences if necessary. The scripts provided here can be used to curate geographic information in the metadata and sample the sequences from any country of interest to ease the preparation of files for Nextstrain and Microreact, thus accelerating evolutionary studies of this important pathogen. CurSa scripts are accessible via: https://github.com/luisdelaye/CurSa/.

Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico.

Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.

Evolution of reduced prokaryotic genomes and the minimal cell concept: variations on a theme.

Prokaryotic genomes of endosymbionts and parasites are examples of naturally evolved minimal cells, the study of which can shed light on life in its minimum form. Their diverse biology, their lack of a large set of orthologous genes and the existence of essential linage (and environmentally) specific genes all illustrate the diversity of genes building up naturally evolved minimal cells. This conclusion is reinforced by the fact that sometimes the same essential function is performed by genes from different evolutionary origins. Nevertheless, all cells perform a set of life-essential functions however different their cell machinery and environment in which they thrive. An upcoming challenge for biologists will be to discern, by studying differences and similarities in current biodiversity, how cells with reduced genomes have adapted while retaining all basic life-supporting functions.

Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America.

Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far. Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (S) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution.

Draft Genome Sequence of a Kazachstania humilis Strain Isolated from Agave Fermentation.

The ascomycetous yeast Kazachstania humilis is an active species in backslopped sourdough and in the spontaneous fermentation of several traditional foods and beverages. Here, we report the draft genome sequence of a K. humilis strain isolated from agave must from a traditional distillery in Mexico.

Twisting development, the birth of a potential new gene.

Evolution has long been considered to be a conservative process in which new genes arise from pre-existing genes through gene duplication, domain shuffling, horizontal transfer, overprinting, retrotransposition, etc. However, this view is changing as new genes originating from non-genic sequences are discovered in different organisms. Still, rather limited functional information is available. Here, we have identified TWISTED1 (TWT1), a possible de novo-originated protein-coding gene that modifies microtubule arrangement and causes helicoidal growth in Arabidopsis thaliana when its expression is increased. Interestingly, even though TWT1 is a likely recent gene, the lack of TWT1 function affects A. thaliana development. TWT1 seems to have originated from a non-genic sequence. If so, it would be one of the few examples to date of how during evolution de novo genes are integrated into developmental cellular and organismal processes.

The Alpha Variant (B.1.1.7) of SARS-CoV-2 Failed to Become Dominant in Mexico.

During the coronavirus disease 2019 (COVID-19) pandemic, the emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the United Kingdom in September 2020, was well documented in different areas of the world and became a global public health concern because of its increased transmissibility. The B.1.1.7 lineage was first detected in Mexico during December 2020, showing a slow progressive increase in its circulation frequency, which reached its maximum in May 2021 but never became predominant. In this work, we analyzed the patterns of diversity and distribution of this lineage in Mexico using phylogenetic and haplotype network analyses. Despite the reported increase in transmissibility of the B.1.1.7 lineage, in most Mexican states, it did not displace cocirculating lineages, such as B.1.1.519, which dominated the country from February to May 2021. Our results show that the states with the highest prevalence of B.1.1.7 were those at the Mexico-U.S. border. An apparent pattern of dispersion of this lineage from the northern states of Mexico toward the center or the southeast was observed in the largest transmission chains, indicating possible independent introduction events from the United States. However, other entry points cannot be excluded, as shown by multiple introduction events. Local transmission led to a few successful haplotypes with a localized distribution and specific mutations indicating sustained community transmission. IMPORTANCE The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021. In this work, we analyzed the distribution of B.1.1.7 in Mexico using phylogenetic and haplotype network analyses. Our results show that the states with the highest prevalence of B.1.1.7 (around 30%) were those at the Mexico-U.S. border, which also exhibited the highest lineage diversity, indicating possible introduction events from the United States. Also, several haplotypes were identified with a localized distribution and specific mutations, indicating that sustained community transmission occurred in the country.

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942.

BACKGROUND: Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. RESULTS: By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. CONCLUSIONS: Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.