Metabolic co-dependence drives the evolutionarily ancient Hydra-Chlorella symbiosis
- Okinawa Institute of Science and Technology Graduate University (OIST), Japan
- Kiel University, Germany
Abstract
Many multicellular organisms rely on symbiotic associations for support of metabolic activity, protection, or energy. Understanding the mechanisms involved in controlling such interactions remains a major challenge. In an unbiased approach we identified key players that control the symbiosis between Hydra viridissima and its photosynthetic symbiont Chlorella sp. A99. We discovered significant up-regulation of Hydra genes encoding a phosphate transporter and glutamine synthetase suggesting regulated nutrition supply between host and symbionts. Interestingly, supplementing the medium with glutamine temporarily supports in vitro growth of the otherwise obligate symbiotic Chlorella, indicating loss of autonomy and dependence on the host. Genome sequencing of Chlorella sp. A99 revealed a large number of amino acid transporters and a degenerated nitrate assimilation pathway, presumably as consequence of the adaptation to the host environment. Our observations portray ancient symbiotic interactions as a codependent partnership in which exchange of nutrients appears to be the primary driving force.
Data availability
Microarray information and the data series are accessible at NCBI GEO under accession number GPL23280 and GSE97633 respectively. All the results of microarray analysis are included in Supplementary Table 1.The Whole Genome Shotgun project of Chlorella sp. A99 has been deposited at DDBJ/ENA/GenBank under the accession PCFQ00000000 (BioProject ID: PRJNA412448). Genome sequences and gene models are also accessible at the website of OIST Marine Genomics Unit Genome Project (http://marinegenomics.oist.jp/chlorellaA99/viewer/info?project_id=65).All data generated by qPCR are included in Source Data: Figure2, Figure2 - Figure supplement 1, Source Data: Figure3, Source Data: Figure3 - Figure Supplement 2 and Source Data: Table 2, Table 4
Article and author information
Author details
Konstantin Khalturin
Funding
Japan Society for the Promotion of Science (Young Scientists (B) 25840132)
- Mayuko Hamada
Japan Society for the Promotion of Science (Scientific Research (C) 15K07173)
- Mayuko Hamada
Deutsche Forschungsgemeinschaft (CRC1182)
- Thomas C G Bosch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paul G Falkowski, Rutgers University, United States
Publication history
- Received: January 16, 2018
- Accepted: May 26, 2018
- Accepted Manuscript published: May 31, 2018 (version 1)
- Version of Record published: June 26, 2018 (version 2)
Copyright
© 2018, Hamada et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Metabolic co-dependence drives the evolutionarily ancient Hydra-Chlorella symbiosis
eLife 7:e35122.
https://doi.org/10.7554/eLife.35122
Further reading
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- Evolutionary Biology
- Medicine
Background:
Abiraterone acetate is an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC), but evolution of resistance inevitably leads to progression. We present a pilot study in which abiraterone dosing is guided by evolution-informed mathematical models to delay onset of resistance.
Methods:
In the study cohort, abiraterone was stopped when PSA was <50% of pretreatment value and resumed when PSA returned to baseline. Results are compared to a contemporaneous cohort who had >50% PSA decline after initial abiraterone administration and met trial eligibility requirements but chose standard of care (SOC) dosing.
Results:
17 subjects were enrolled in the adaptive therapy group and 16 in the SOC group. All SOC subjects have progressed, but four patients in the study cohort remain stably cycling (range 53–70 months). The study cohort had significantly improved median time to progression (TTP; 33.5 months; p<0.001) and median overall survival (OS; 58.5 months; hazard ratio, 0.41, 95% confidence interval (CI), 0.20–0.83, p<0.001) compared to 14.3 and 31.3 months in the SOC cohort. On average, study subjects received no abiraterone during 46% of time on trial. Longitudinal trial data demonstrated the competition coefficient ratio (αRS/αSR) of sensitive and resistant populations, a critical factor in intratumoral evolution, was two- to threefold higher than pre-trial estimates. Computer simulations of intratumoral evolutionary dynamics in the four long-term survivors found that, due to the larger value for αRS/αSR, cycled therapy significantly decreased the resistant population. Simulations in subjects who progressed predicted further increases in OS could be achieved with prompt abiraterone withdrawal after achieving 50% PSA reduction.
Conclusions:
Incorporation of evolution-based mathematical models into abiraterone monotherapy for mCRPC significantly increases TTP and OS. Computer simulations with updated parameters from longitudinal trial data can estimate intratumoral evolutionary dynamics in each subject and identify strategies to improve outcomes.
Funding:
Moffitt internal grants and NIH/NCI U54CA143970-05 (Physical Science Oncology Network).
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- Epidemiology and Global Health
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Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here, we fully characterise the evolutionary dynamics of these MGEs using a collection of 1180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline, and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398 have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.
