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Genetic innovations in animal–microbe symbioses

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Abstract

Animal hosts have initiated myriad symbiotic associations with microorganisms and often have maintained these symbioses for millions of years, spanning drastic changes in ecological conditions and lifestyles. The establishment and persistence of these relationships require genetic innovations on the parts of both symbionts and hosts. The nature of symbiont innovations depends on their genetic population structure, categorized here as open, closed or mixed. These categories reflect modes of inter-host transmission that result in distinct genomic features, or genomic syndromes, in symbionts. Although less studied, hosts also innovate in order to preserve and control symbiotic partnerships. New capabilities to sequence host-associated microbial communities and to experimentally manipulate both hosts and symbionts are providing unprecedented insights into how genetic innovations arise under different symbiont population structures and how these innovations function to support symbiotic relationships.

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Fig. 1: Symbiont genetic population structure.
Fig. 2: Genomic features of bacterial species that have evolved under open, closed and mixed symbioses.
Fig. 3: Symbiont phylogenetic patterns depend on the frequency of horizontal transmission.
Fig. 4: Common features and mechanisms of innovation in open symbiotic communities.
Fig. 5: Common features and mechanisms of innovation in closed symbiotic communities.
Fig. 6: Common features and mechanisms of innovation in mixed symbiotic communities.
Fig. 7: Commonly used tools for the study of symbiont genetics.

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References

  1. McFall-Ngai, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl Acad. Sci. USA 110, 3229–3236 (2013).

    PubMed  PubMed Central  CAS  Google Scholar 

  2. Moran, N. A., McCutcheon, J. P. & Nakabachi, A. Genomics and evolution of heritable bacterial symbionts. Annu. Rev. Genet. 42, 165–190 (2008).

    PubMed  CAS  Google Scholar 

  3. Wernegreen, J. J. Ancient bacterial endosymbionts of insects: genomes as sources of insight and springboards for inquiry. Exp. Cell Res. 358, 427–432 (2017).

    PubMed  CAS  Google Scholar 

  4. Shigenobu, S. & Wilson, A. C. C. Genomic revelations of a mutualism: the pea aphid and its obligate bacterial symbiont. Cell. Mol. Life Sci. 68, 1297–1309 (2011).

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Bongrand, C. et al. Using colonization assays and comparative genomics to discover symbiosis behaviors and factors in Vibrio fischeri. mBio 11, e03407-19 (2020).

    PubMed  PubMed Central  Google Scholar 

  6. McCutcheon, J. P., Boyd, B. M. & Dale, C. The life of an insect endosymbiont from the cradle to the grave. Curr. Biol. 29, R485–R495 (2019).

    PubMed  CAS  Google Scholar 

  7. Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S. & Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 568, 505–510 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  8. Jäckle, O. et al. Chemosynthetic symbiont with a drastically reduced genome serves as primary energy storage in the marine flatworm Paracatenula. Proc. Natl Acad. Sci. USA 116, 8505–8514 (2019). The intracellular symbiont of Paracatenula flatworms possesses a highly reduced genome (1.34 Mb) and represents the oldest documented animal symbiosis (500 My); this article shows that it provisions its host through outer membrane vesicle secretion.

    PubMed  PubMed Central  Google Scholar 

  9. Masson, F. & Lemaitre, B. Growing ungrowable bacteria: overview and perspectives on insect symbiont culturability. Microbiol. Mol. Biol. Rev. 84, e00089-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  10. Elston, K. M., Leonard, S. P., Geng, P., Bialik, S. B. & Barrick, J. E. Engineering insects from the endosymbiont out. Trends Microbiol. https://doi.org/10.1016/j.tim.2021.05.004 (2021).

    Article  PubMed  Google Scholar 

  11. Kirchberger, P. C., Schmidt, M. & Ochman, H. The ingenuity of bacterial genomes. Annu. Rev. Microbiol. 74, 815–834 (2020).

    PubMed  CAS  Google Scholar 

  12. Bennett, G. M. & Moran, N. A. Heritable symbiosis: The advantages and perils of an evolutionary rabbit hole. Proc. Natl Acad. Sci. USA 112, 10169–10176 (2015).

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Husnik, F. & Keeling, P. J. The fate of obligate endosymbionts: reduction, integration, or extinction. Curr. Opin. Genet. Dev. 58-59, 1–8 (2019).

    PubMed  CAS  Google Scholar 

  14. Sudakaran, S., Kost, C. & Kaltenpoth, M. Symbiont acquisition and replacement as a source of ecological innovation. Trends Microbiol. 25, 375–390 (2017).

    PubMed  CAS  Google Scholar 

  15. Husnik, F. & McCutcheon, J. P. Functional horizontal gene transfer from bacteria to eukaryotes. Nat. Rev. Microbiol. 16, 67–79 (2018).

    PubMed  CAS  Google Scholar 

  16. Salem, H., Florez, L., Gerardo, N. & Kaltenpoth, M. An out-of-body experience: the extracellular dimension for the transmission of mutualistic bacteria in insects. Proc. Biol. Sci. 282, 20142957 (2015).

    PubMed  PubMed Central  Google Scholar 

  17. Bright, M. & Bulgheresi, S. A complex journey: transmission of microbial symbionts. Nat. Rev. Microbiol. 8, 218–230 (2010).

    PubMed  PubMed Central  CAS  Google Scholar 

  18. McCutcheon, J. P. & Moran, N. A. Extreme genome reduction in symbiotic bacteria. Nat. Rev. Microbiol. 10, 13–26 (2011).

    PubMed  Google Scholar 

  19. Foster, K. R., Schluter, J., Coyte, K. Z. & Rakoff-Nahoum, S. The evolution of the host microbiome as an ecosystem on a leash. Nature 548, 43–51 (2017).

    PubMed  PubMed Central  CAS  Google Scholar 

  20. Garud, N. R., Good, B. H., Hallatschek, O. & Pollard, K. S. Evolutionary dynamics of bacteria in the gut microbiome within and across hosts. PLoS Biol. 17, e3000102 (2019). This study used a novel metagenomics-based approach to study the evolution of 40 bacterial species in the human gut and found signatures of within-host adaptation occurring over short timescales (6–12 months).

    PubMed  PubMed Central  Google Scholar 

  21. Bobay, L.-M. & Raymann, K. Population genetics of host-associated microbiomes. Curr. Mol. Biol. Rep. 5, 128–139 (2019).

    Google Scholar 

  22. Van Rossum, T., Ferretti, P., Maistrenko, O. M. & Bork, P. Diversity within species: interpreting strains in microbiomes. Nat. Rev. Microbiol. 18, 491–506 (2020).

    PubMed  PubMed Central  Google Scholar 

  23. Kikuchi, Y., Ohbayashi, T., Jang, S. & Mergaert, P. Burkholderia insecticola triggers midgut closure in the bean bug Riptortus pedestris to prevent secondary bacterial infections of midgut crypts. ISME J. 14, 1627–1638 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  24. de Oliveira, B. F. R., Freitas-Silva, J., Sánchez-Robinet, C. & Laport, M. S. Transmission of the sponge microbiome: moving towards a unified model. Environ. Microbiol. Rep. 12, 619–638 (2020).

    PubMed  Google Scholar 

  25. Ansorge, R. et al. Functional diversity enables multiple symbiont strains to coexist in deep-sea mussels. Nat. Microbiol. 4, 2487–2497 (2019).

    PubMed  Google Scholar 

  26. Picazo, D. R. et al. Horizontally transmitted symbiont populations in deep-sea mussels are genetically isolated. ISME J. 13, 2954–2968 (2019).

    Google Scholar 

  27. Moran, N. A. & Bennett, G. M. The tiniest tiny genomes. Annu. Rev. Microbiol. 68, 195–215 (2014).

    PubMed  CAS  Google Scholar 

  28. Gruber-Vodicka, H. R. et al. Paracatenula, an ancient symbiosis between thiotrophic Alphaproteobacteria and catenulid flatworms. Proc. Natl Acad. Sci. USA 108, 12078–12083 (2011).

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Baker, L. J. et al. Diverse deep-sea anglerfishes share a genetically reduced luminous symbiont that is acquired from the environment. eLife 8, e47606 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Koga, R., Meng, X.-Y., Tsuchida, T. & Fukatsu, T. Cellular mechanism for selective vertical transmission of an obligate insect symbiont at the bacteriocyte–embryo interface. Proc. Natl Acad. Sci. USA 109, E1230–E1237 (2012).

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Salem, H., Bauer, E., Kirsch, R., Berasategui, A. & Cripps, M. Drastic genome reduction in an herbivore’s pectinolytic symbiont. Cell 171, 1520–1531 (2017).

    PubMed  CAS  Google Scholar 

  32. Mondal, S. I. et al. Reduced genome of the gut symbiotic bacterium “Candidatus Benitsuchiphilus tojoi” provides insight into its possible roles in ecology and adaptation of the host insect’. Front. Microbiol. 11, 840 (2020).

    PubMed  PubMed Central  Google Scholar 

  33. Kaiwa, N. et al. Symbiont-supplemented maternal investment underpinning host’s ecological adaptation. Curr. Biol. 24, 2465–2470 (2014).

    PubMed  CAS  Google Scholar 

  34. Koga, R. et al. Host’s guardian protein counters degenerative symbiont evolution. Proc. Natl Acad. Sci. USA 118, e2103957118 (2021).

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Kehr, J.-C. & Dittmann, E. Protective tunicate endosymbiont with extreme genome reduction. Environ. Microbiol. 17, 3430–3432 (2015).

    PubMed  Google Scholar 

  36. Russell, S. L. et al. Horizontal transmission and recombination maintain forever young bacterial symbiont genomes. PLoS Genet. 16, e1008935 (2020). This study sequenced chemosynthetic symbionts from a variety of bivalve hosts in which transmission modes ranged from strictly horizontal to almost entirely vertical. Results revealed corresponding variation in the extent of genome erosion and rates of homologous recombination.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. George, E. E. et al. Highly reduced genomes of protist endosymbionts show evolutionary convergence. Curr. Biol. 30, 925–933 (2020).

    PubMed  CAS  Google Scholar 

  38. Vavre, F., Fleury, F., Lepetit, D., Fouillet, P. & Boulétreau, M. Phylogenetic evidence for horizontal transmission of Wolbachia in host-parasitoid associations. Mol. Biol. Evol. 16, 1711–1723 (1999).

    PubMed  CAS  Google Scholar 

  39. Russell, J. A., Latorre, A., Sabater-Muñoz, B., Moya, A. & Moran, N. A. Side-stepping secondary symbionts: widespread horizontal transfer across and beyond the Aphidoidea. Mol. Ecol. 12, 1061–1075 (2003).

    PubMed  CAS  Google Scholar 

  40. Gerth, M. et al. Rapid molecular evolution of Spiroplasma symbionts of Drosophila. Microb. Genom. 7, 000503 (2021).

    PubMed Central  CAS  Google Scholar 

  41. Frost, C. L. et al. The hypercomplex genome of an insect reproductive parasite highlights the importance of lateral gene transfer in symbiont biology. mBio 11, e02590-19 (2020).

    PubMed  PubMed Central  Google Scholar 

  42. Chong, R. A., Park, H. & Moran, N. A. Genome evolution of the obligate endosymbiont Buchnera aphidicola. Mol. Biol. Evol. 36, 1481–1489 (2019).

    PubMed  CAS  Google Scholar 

  43. Chevignon, G., Boyd, B. M., Brandt, J. W., Oliver, K. M. & Strand, M. R. Culture-facilitated comparative genomics of the facultative symbiont Hamiltonella defensa. Genome Biol. Evol. 10, 786–802 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  44. Russell, S. L., Corbett-Detig, R. B. & Cavanaugh, C. M. Mixed transmission modes and dynamic genome evolution in an obligate animal–bacterial symbiosis. ISME J. 11, 1359–1371 (2017).

    PubMed  PubMed Central  Google Scholar 

  45. Asselin, A. K., Villegas-Ospina, S., Hoffmann, A. A., Brownlie, J. C. & Johnson, K. N. Contrasting patterns of virus protection and functional incompatibility genes in two conspecific Wolbachia strains from Drosophila pandora. Appl. Environ. Microbiol. 85, e02290-18 (2019).

    PubMed  PubMed Central  Google Scholar 

  46. Martinez, J. et al. Symbiont strain is the main determinant of variation in Wolbachia-mediated protection against viruses across Drosophila species. Mol. Ecol. 26, 4072–4084 (2017).

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Newton, I. L. G. & Rice, D. W. The Jekyll and Hyde symbiont: could Wolbachia be a nutritional mutualist? J. Bacteriol. 202, e00589-19 (2020).

    PubMed  PubMed Central  Google Scholar 

  48. Tokuda, G. et al. Fiber-associated spirochetes are major agents of hemicellulose degradation in the hindgut of wood-feeding higher termites. Proc. Natl Acad. Sci. USA 115, E11996–E12004 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  49. Kwong, W. K. & Moran, N. A. Gut microbial communities of social bees. Nat. Rev. Microbiol. 14, 374–384 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Bongrand, C. & Ruby, E. G. Achieving a multi-strain symbiosis: strain behavior and infection dynamics. ISME J. 13, 698–706 (2019). The squid light organ symbiosis involves only a single bacterial species, but this study, based on experimental colonization of hosts with combinations of isolates, reveals distinct bacterial strategies for competing and persisting within hosts.

    PubMed  Google Scholar 

  51. Pietschke, C. et al. Host modification of a bacterial quorum-sensing signal induces a phenotypic switch in bacterial symbionts. Proc. Natl Acad. Sci. USA 114, E8488–E8497 (2017).

    PubMed  PubMed Central  CAS  Google Scholar 

  52. Lo, W.-S., Huang, Y.-Y. & Kuo, C.-H. Winding paths to simplicity: genome evolution in facultative insect symbionts. FEMS Microbiol. Rev. 40, 855–874 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Waterworth, S. C. et al. Horizontal gene transfer to a defensive symbiont with a reduced genome in a multipartite beetle microbiome. mBio 11, e02430-19 (2020). While most highly reduced symbiont genomes show no evidence of gene acquisition, this study revealed an exception: the extracellular symbiont of the beetle Lagria villosa acquired beneficial genes through HGT, even while undergoing massive genome reduction.

    PubMed  PubMed Central  Google Scholar 

  54. Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212–215 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  55. Blaser, M. J. Missing Microbes: How the Overuse of Antibiotics is Fueling our Modern Plagues, Vol. 20 (Macmillan, 2014).

  56. Daisley, B. A., Chmiel, J. A., Pitek, A. P., Thompson, G. J. & Reid, G. Missing microbes in bees: How systematic depletion of key symbionts erodes immunity. Trends Microbiol. 28, 1010–1021 (2020).

    PubMed  CAS  Google Scholar 

  57. Moeller, A. H. et al. Cospeciation of gut microbiota with hominids. Science 353, 380–382 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Moeller, A. H., Suzuki, T. A., Phifer-Rixey, M. & Nachman, M. W. Transmission modes of the mammalian gut microbiota. Science 362, 453–457 (2018).

    PubMed  CAS  Google Scholar 

  59. Bourguignon, T. et al. Rampant host switching shaped the termite gut microbiome. Curr. Biol. 28, 649–654.e2 (2018).

    PubMed  CAS  Google Scholar 

  60. Powell, J. E., Martinson, V. G., Urban-Mead, K. & Moran, N. A. Routes of acquisition of the gut microbiota of the honey bee Apis mellifera. Appl. Environ. Microbiol. 80, 7378–7387 (2014).

    PubMed  PubMed Central  Google Scholar 

  61. Yassour, M. et al. Strain-level analysis of mother-to-child bacterial transmission during the first few months of life. Cell Host Microbe 24, 146–154.e4 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  62. Kwong, W. K. et al. Dynamic microbiome evolution in social bees. Sci. Adv. 3, e1600513 (2017).

    PubMed  PubMed Central  Google Scholar 

  63. Ohbayashi, T. et al. Insect’s intestinal organ for symbiont sorting. Proc. Natl Acad. Sci. USA 112, E5179–E5188 (2015).

    PubMed  PubMed Central  CAS  Google Scholar 

  64. Itoh, H. et al. Host–symbiont specificity determined by microbe–microbe competition in an insect gut. Proc. Natl Acad. Sci. USA 116, 22673–22682 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Visick, K. L., Foster, J., Doino, J., McFall-Ngai, M. & Ruby, E. G. Vibrio fischeri lux genes play an important role in colonization and development of the host light organ. J. Bacteriol. 182, 4578–4586 (2000).

    PubMed  PubMed Central  CAS  Google Scholar 

  66. Moriano-Gutierrez, S. et al. Critical symbiont signals drive both local and systemic changes in diel and developmental host gene expression. Proc. Natl Acad. Sci. USA 116, 7990–7999 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Thompson, C. M., Tischler, A. H., Tarnowski, D. A., Mandel, M. J. & Visick, K. L. Nitric oxide inhibits biofilm formation by Vibrio fischeri via the nitric oxide sensor HnoX. Mol. Microbiol. 111, 187–203 (2019).

    PubMed  CAS  Google Scholar 

  68. Essock-Burns, T., Bongrand, C., Goldman, W. E., Ruby, E. G. & McFall-Ngai, M. J. Interactions of symbiotic partners drive the development of a complex biogeography in the squid-Vibrio symbiosis. mBio 11, e00853–20 (2020).

    PubMed  PubMed Central  Google Scholar 

  69. Raina, J.-B., Fernandez, V., Lambert, B., Stocker, R. & Seymour, J. R. The role of microbial motility and chemotaxis in symbiosis. Nat. Rev. Microbiol. 17, 284–294 (2019).

    PubMed  CAS  Google Scholar 

  70. Robinson, C. D. et al. Experimental bacterial adaptation to the zebrafish gut reveals a primary role for immigration. PLoS Biol. 16, e2006893 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  71. Lebov, J. F., Schlomann, B. H., Robinson, C. D. & Bohannan, B. J. M. Phenotypic parallelism during experimental adaptation of a free-living bacterium to the zebrafish gut. mBio 11, e01519-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  72. Erturk-Hasdemir, D. et al. Symbionts exploit complex signaling to educate the immune system. Proc. Natl Acad. Sci. USA 116, 26157–26166 (2019).

    PubMed Central  CAS  Google Scholar 

  73. Wexler, A. G. et al. Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins. eLife 7, e37138 (2018).

    PubMed  PubMed Central  Google Scholar 

  74. Putnam, E. E. & Goodman, A. L. B vitamin acquisition by gut commensal bacteria. PLoS Pathog. 16, e1008208 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  75. Coyne, M. J. & Comstock, L. E. Type VI secretion systems and the gut microbiota. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.PSIB-0009-2018 (2019).

    Article  PubMed  Google Scholar 

  76. Steele, M. I., Kwong, W. K., Whiteley, M. & Moran, N. A. Diversification of type VI secretion system toxins reveals ancient antagonism among bee gut microbes. mBio 8, e01630-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  77. Speare, L. et al. Bacterial symbionts use a type VI secretion system to eliminate competitors in their natural host. Proc. Natl Acad. Sci. USA 115, E8528–E8537 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  78. Baquero, F., Lanza, V. F., Baquero, M.-R., Del Campo, R. & Bravo-Vázquez, D. A. Microcins in Enterobacteriaceae: peptide antimicrobials in the eco-active intestinal chemosphere. Front. Microbiol. 10, 2261 (2019).

    PubMed  PubMed Central  Google Scholar 

  79. Frazão, N., Sousa, A., Lässig, M. & Gordo, I. Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut. Proc. Natl Acad. Sci. USA 116, 17906–17915 (2019). Using experimental evolution of a target E. coli strain introduced to hosts with resident microbiomes, this study found that bacteriophage-mediated HGT is a strong force mediating the evolution of E. coli in the mouse gut.

    PubMed  PubMed Central  Google Scholar 

  80. Ramiro, R. S., Durão, P., Bank, C. & Gordo, I. Low mutational load and high mutation rate variation in gut commensal bacteria. PLoS Biol. 18, e3000617 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  81. Brockhurst, M. A. et al. The ecology and evolution of pangenomes. Curr. Biol. 29, R1094–R1103 (2019).

    PubMed  CAS  Google Scholar 

  82. Pasolli, E. et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell 176, 649–662.e20 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  83. Vatanen, T. et al. Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life. Nat. Microbiol. 4, 470–479 (2019).

    PubMed  CAS  Google Scholar 

  84. Ludvigsen, J., Porcellato, D. & L’Abée-Lund, T. M. Geographically widespread honeybee-gut symbiont subgroups show locally distinct antibiotic-resistant patterns. Mol. Ecol. 26, 6590–6607 (2017).

    PubMed  CAS  Google Scholar 

  85. Zheng, H. et al. Metabolism of toxic sugars by strains of the bee gut symbiont Gilliamella apicola. mBio 7, e01326–16 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  86. Jahn, M. T. et al. A phage protein aids bacterial symbionts in eukaryote immune evasion. Cell Host Microbe 26, 542–550.e5 (2019).

    PubMed  CAS  Google Scholar 

  87. Wexler, A. G. et al. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proc. Natl Acad. Sci. USA 113, 3639–3644 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  88. Ross, B. D. et al. Human gut bacteria contain acquired interbacterial defence systems. Nature 575, 224–228 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  89. Sonnenburg, E. D. et al. Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell 141, 1241–1252 (2010).

    PubMed  PubMed Central  CAS  Google Scholar 

  90. Fehlner-Peach, H. et al. Distinct polysaccharide utilization profiles of human intestinal Prevotella copri isolates. Cell Host Microbe 26, 680–690.e5 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  91. Zheng, H. et al. Division of labor in honey bee gut microbiota for plant polysaccharide digestion. Proc. Natl Acad. Sci. USA 116, 25909–25916 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  92. Hehemann, J.-H., Kelly, A. G., Pudlo, N. A., Martens, E. C. & Boraston, A. B. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proc. Natl Acad. Sci. USA 109, 19786–19791 (2012).

    PubMed  PubMed Central  CAS  Google Scholar 

  93. Kent, A. G., Vill, A. C., Shi, Q., Satlin, M. J. & Brito, I. L. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat. Commun. 11, 4379 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  94. Foster, K. R. & Bell, T. Competition, not cooperation, dominates interactions among culturable microbial species. Curr. Biol. 22, 1845–1850 (2012).

    PubMed  CAS  Google Scholar 

  95. Machado, D. et al. Polarization of microbial communities between competitive and cooperative metabolism. Nat. Ecol. Evol. 5, 195–203 (2021).

    PubMed  PubMed Central  Google Scholar 

  96. Morris, J. J., Lenski, R. E. & Zinser, E. R. The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss. mBio 3, 300036–300012 (2012).

    Google Scholar 

  97. Preussger, D., Giri, S., Muhsal, L. K., Oña, L. & Kost, C. Reciprocal fitness feedbacks promote the evolution of mutualistic cooperation. Curr. Biol. 30, 3580–3590.e7 (2020).

    PubMed  CAS  Google Scholar 

  98. Salem, H. et al. Symbiont digestive range reflects host plant breadth in herbivorous beetles. Curr. Biol. 30, 2875–2886.e4 (2020). Genome sequences for 13 strains of Stammera, the extracellular symbiont of leaf beetles, revealed that strains differ in metabolic capabilities, potentially shaping the host ecological range.

    PubMed  CAS  Google Scholar 

  99. Hansen, A. K. & Moran, N. A. Altered tRNA characteristics and 3′ maturation in bacterial symbionts with reduced genomes. Nucleic Acids Res. 40, 7870–7884 (2012).

    PubMed  PubMed Central  CAS  Google Scholar 

  100. Van Leuven, J. T., Mao, M., Xing, D. D., Bennett, G. M. & McCutcheon, J. P. Cicada endosymbionts have tRNAs that are correctly processed despite having genomes that do not encode all of the tRNA processing machinery. mBio 10, e01950-18 (2019).

    PubMed  PubMed Central  Google Scholar 

  101. Melnikov, S. V., van den Elzen, A., Stevens, D. L., Thoreen, C. C. & Söll, D. Loss of protein synthesis quality control in host-restricted organisms. Proc. Natl Acad. Sci. USA 115, E11505–E11512 (2018). This study shows that most host-restricted, small genome symbionts possess aminoacyl-tRNA synthetases with degraded editing sites, suggesting error-prone translation and demonstrating that even retained genes in eroded genomes have compromised functionality.

    PubMed  PubMed Central  CAS  Google Scholar 

  102. Bourguignon, T. et al. Increased mutation rate is linked to genome reduction in prokaryotes. Curr. Biol. 30, 3848–3855.e4 (2020).

    PubMed  CAS  Google Scholar 

  103. Bennett, G. M. & Mao, M. Comparative genomics of a quadripartite symbiosis in a planthopper host reveals the origins and rearranged nutritional responsibilities of anciently diverged bacterial lineages. Environ. Microbiol. 20, 4461–4472 (2018).

    PubMed  CAS  Google Scholar 

  104. Nakabachi, A. & Okamura, K. Diaphorin, a polyketide produced by a bacterial symbiont of the Asian citrus psyllid, kills various human cancer cells. PLoS One 14, e0218190 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  105. Nakabachi, A., Piel, J., Malenovský, I. & Hirose, Y. Comparative genomics underlines multiple roles of Profftella, an obligate symbiont of psyllids: providing toxins, vitamins, and carotenoids. Genome Biol. Evol. 12, 1975–1987 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  106. Reis, F. et al. Bacterial symbionts support larval sap feeding and adult folivory in (semi-) aquatic reed beetles. Nat. Commun. 11, 2964 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  107. Luan, J., Sun, X., Fei, Z. & Douglas, A. E. Maternal inheritance of a single somatic animal cell displayed by the bacteriocyte in the whitefly Bemisia tabaci. Curr. Biol. 28, 459–465.e3 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  108. Rio, R. V. M. et al. Insight into the transmission biology and species-specific functional capabilities of tsetse (Diptera: Glossinidae) obligate symbiont Wigglesworthia. mBio 3, e00240–11 (2012).

    PubMed  PubMed Central  CAS  Google Scholar 

  109. Maire, J. et al. Spatial and morphological reorganization of endosymbiosis during metamorphosis accommodates adult metabolic requirements in a weevil. Proc. Natl Acad. Sci. USA 117, 19347–19358 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  110. Campbell, M. A. et al. Genome expansion via lineage splitting and genome reduction in the cicada endosymbiont Hodgkinia. Proc. Natl Acad. Sci. USA 112, 10192–10199 (2015).

    PubMed  PubMed Central  CAS  Google Scholar 

  111. Campbell, M. A., Łukasik, P., Simon, C. & McCutcheon, J. P. Idiosyncratic genome degradation in a bacterial endosymbiont of periodical cicadas. Curr. Biol. 27, 3568–3575.e3 (2017).

    PubMed  CAS  Google Scholar 

  112. Price, D. R. G. & Wilson, A. C. C. A substrate ambiguous enzyme facilitates genome reduction in an intracellular symbiont. BMC Biol. 12, 110 (2014).

    PubMed  PubMed Central  Google Scholar 

  113. Zhang, B., Leonard, S. P., Li, Y. & Moran, N. A. Obligate bacterial endosymbionts limit thermal tolerance of insect host species. Proc. Natl Acad. Sci. USA 116, 24712–24718 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  114. Fan, Y. & Wernegreen, J. J. Can’t take the heat: high temperature depletes bacterial endosymbionts of ants. Microb. Ecol. 66, 727–733 (2013).

    PubMed  PubMed Central  Google Scholar 

  115. Kupper, M., Gupta, S. K., Feldhaar, H. & Gross, R. Versatile roles of the chaperonin GroEL in microorganism-insect interactions. FEMS Microbiol. Lett. 353, 1–10 (2014).

    PubMed  CAS  Google Scholar 

  116. Fares, M. A., Ruiz-González, M. X., Moya, A., Elena, S. F. & Barrio, E. GroEL buffers against deleterious mutations. Nature 417, 398 (2002).

    PubMed  CAS  Google Scholar 

  117. Poliakov, A. et al. Large-scale label-free quantitative proteomics of the pea aphid-Buchnera symbiosis. Mol. Cell. Proteom. 10, M110.007039 (2011).

    Google Scholar 

  118. Husnik, F. et al. Horizontal gene transfer from diverse bacteria to an insect genome enables a tripartite nested mealybug symbiosis. Cell 153, 1567–1578 (2013).

    PubMed  CAS  Google Scholar 

  119. Bublitz, D. C. et al. Peptidoglycan production by an insect-bacterial mosaic. Cell 179, 703–712 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  120. Nikoh, N. & Nakabachi, A. Aphids acquired symbiotic genes via lateral gene transfer. BMC Biol. 7, 12 (2009).

    PubMed  PubMed Central  Google Scholar 

  121. Mao, M., Yang, X. & Bennett, G. M. Evolution of host support for two ancient bacterial symbionts with differentially degraded genomes in a leafhopper host. Proc. Natl Acad. Sci. USA 115, E11691–E11700 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  122. Matsuura, Y. et al. Recurrent symbiont recruitment from fungal parasites in cicadas. Proc. Natl Acad. Sci. USA 115, E5970–E5979 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  123. Manzano-Marín, A., Szabó, G., Simon, J., Horn, M. & Latorre, A. Happens in the best of subfamilies: establishment and repeated replacements of co-obligate secondary endosymbionts within Lachninae aphids. Environ. Microbiol. 19, 393–408 (2017).

    PubMed  Google Scholar 

  124. Duron, O. et al. Tick-bacteria mutualism depends on B vitamin synthesis pathways. Curr. Biol. 28, 1896–1902.e5 (2018).

    PubMed  CAS  Google Scholar 

  125. Mao, M. & Bennett, G. M. Symbiont replacements reset the co-evolutionary relationship between insects and their heritable bacteria. ISME J. 14, 1384–1395 (2020).

    PubMed  PubMed Central  Google Scholar 

  126. Feng, H., Edwards, N. & Anderson, C. M. H. Trading amino acids at the aphid–Buchnera symbiotic interface. Proc. Natl Acad. Sci. USA 116, 16003–16011 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  127. Lu, H.-L., Chang, C.-C. & Wilson, A. C. C. Amino acid transporters implicated in endocytosis of Buchnera during symbiont transmission in the pea aphid. Evodevo 7, 24 (2016).

    PubMed  PubMed Central  Google Scholar 

  128. Gerardo, N. M. et al. Immunity and other defenses in pea aphids, Acyrthosiphon pisum. Genome Biol. 11, R21 (2010).

    PubMed  PubMed Central  Google Scholar 

  129. Gerardo, N. M., Hoang, K. L. & Stoy, K. S. Evolution of animal immunity in the light of beneficial symbioses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 375, 20190601 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  130. Chung, S. H., Jing, X., Luo, Y. & Douglas, A. E. Targeting symbiosis-related insect genes by RNAi in the pea aphid-Buchnera symbiosis. Insect Biochem. Mol. Biol. 95, 55–63 (2018).

    PubMed  CAS  Google Scholar 

  131. Maire, J. et al. Weevil pgrp-lb prevents endosymbiont TCT dissemination and chronic host systemic immune activation. Proc. Natl Acad. Sci. USA 116, 5623–5632 (2019). This study shows that hosts can evolve to limit their own immune response to beneficial symbionts: cereal weevils use a bacteriocyte-specific isoform of peptidoglycan recognition protein to cleave peptidoglycan monomers of Sodalis symbionts, preventing the costly activation of their immune system by their symbiont’s peptidoglycan.

    PubMed  PubMed Central  CAS  Google Scholar 

  132. Kobiałka, M., Michalik, A., Walczak, M., Junkiert, L. & Szklarzewicz, T. Sulcia symbiont of the leafhopper Macrosteles laevis (Ribaut, 1927) (Insecta, Hemiptera, Cicadellidae: Deltocephalinae) harbors Arsenophonus bacteria. Protoplasma 253, 903–912 (2016).

    PubMed  Google Scholar 

  133. Husnik, F. & McCutcheon, J. P. Repeated replacement of an intrabacterial symbiont in the tripartite nested mealybug symbiosis. Proc. Natl Acad. Sci. USA 113, E5416–E5424 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  134. Michalik, A., Jankowska, W., Kot, M., Gołas, A. & Szklarzewicz, T. Symbiosis in the green leafhopper, Cicadella viridis (Hemiptera, Cicadellidae). Association in statu nascendi? Arthropod Struct. Dev. 43, 579–587 (2014).

    PubMed  Google Scholar 

  135. Scholz, M. et al. Large scale genome reconstructions illuminate Wolbachia evolution. Nat. Commun. 11, 5235 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  136. Sanaei, E., Charlat, S. & Engelstädter, J. Wolbachia host shifts: routes, mechanisms, constraints and evolutionary consequences. Biol. Rev. Camb. Philos. Soc. 96, 433–453 (2020).

    PubMed  Google Scholar 

  137. Herren, J. K., Paredes, J. C., Schüpfer, F. & Lemaitre, B. Vertical transmission of a Drosophila endosymbiont via cooption of the yolk transport and internalization machinery. mBio 4, e00532-12 (2013).

    PubMed  PubMed Central  Google Scholar 

  138. Perreau, J. et al. Vertical transmission at the pathogen-symbiont interface: Serratia symbiotica and aphids. mBio 12, e00359-21 (2021).

    PubMed  PubMed Central  Google Scholar 

  139. Koga, R., Bennett, G. M., Cryan, J. R. & Moran, N. A. Evolutionary replacement of obligate symbionts in an ancient and diverse insect lineage. Environ. Microbiol. 15, 2073–2081 (2013).

    PubMed  Google Scholar 

  140. Medina Munoz, M., Spencer, N., Enomoto, S., Dale, C. & Rio, R. V. M. Quorum sensing sets the stage for the establishment and vertical transmission of Sodalis praecaptivus in tsetse flies. PLoS Genet. 16, e1008992 (2020). Experiments using gene knockouts and artificial inoculations of hosts showed that the culturable proto-symbiont Sodalis praecaptivus can use quorum sensing to quickly attenuate its virulence and achieve vertical transmission in a novel host.

    PubMed  PubMed Central  CAS  Google Scholar 

  141. Hurst, G. D. D. & Frost, C. L. Reproductive parasitism: maternally inherited symbionts in a biparental world. Cold Spring Harb. Perspect. Biol. 7, a017699 (2015).

    PubMed  PubMed Central  Google Scholar 

  142. Harumoto, T., Fukatsu, T. & Lemaitre, B. Common and unique strategies of male killing evolved in two distinct Drosophila symbionts. Proc. R. Soc. B 285, 20172167 (2018).

    PubMed  PubMed Central  Google Scholar 

  143. Harumoto, T. & Lemaitre, B. Male-killing toxin in a bacterial symbiont of Drosophila. Nature 557, 252–255 (2018). This study determined that male-killing by a Spiroplasma symbiont of Drosophila is caused by a toxin that targets dosage compensation machinery on the male X chromosome.

    PubMed  PubMed Central  CAS  Google Scholar 

  144. Shropshire, J. D., Rosenberg, R. & Bordenstein, S. R. The impacts of cytoplasmic incompatibility factor (cifA and cifB) genetic variation on phenotypes. Genetics 217, iyaa007 (2020). This study illustrates the power of using a model host species (Drosophila melanogaster) in studies of unculturable symbionts, in this case, Wolbachia. To explore cytoplasmic incompatibility phenotypes imposed by prophage genes, transgenic Drosophila melanogaster were engineered to express versions of cifA and cifB from related fly species, resulting in specific incompatibility outcomes for particular combinations.

    PubMed Central  Google Scholar 

  145. LePage, D. P. et al. Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility. Nature 543, 243–247 (2017).

    PubMed  PubMed Central  CAS  Google Scholar 

  146. Martinez, J., Klasson, L., Welch, J. J. & Jiggins, F. M. Life and death of selfish genes: comparative genomics reveals the dynamic evolution of cytoplasmic incompatibility. Mol. Biol. Evol. 38, 2–15 (2020).

    PubMed Central  Google Scholar 

  147. Hill, T., Unckless, R. L. & Perlmutter, J. I. Rapid evolution and horizontal gene transfer in the genome of a male-killing Wolbachia. bioRxiv https://doi.org/10.1101/2020.11.16.385294 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Ballinger, M. J., Gawryluk, R. M. R. & Perlman, S. J. Toxin and genome evolution in a Drosophila defensive symbiosis. Genome Biol. Evol. 11, 253–262 (2019).

    PubMed  CAS  Google Scholar 

  149. Oliver, K. M., Degnan, P. H., Hunter, M. S. & Moran, N. A. Bacteriophages encode factors required for protection in a symbiotic mutualism. Science 325, 992–994 (2009).

    PubMed  PubMed Central  CAS  Google Scholar 

  150. Brandt, J. W., Chevignon, G., Oliver, K. M. & Strand, M. R. Culture of an aphid heritable symbiont demonstrates its direct role in defence against parasitoids. Proc. Biol. Sci. 284, 20171925 (2017).

    PubMed  PubMed Central  Google Scholar 

  151. Oliver, K. M., Degnan, P. H., Burke, G. R. & Moran, N. A. Facultative symbionts in aphids and the horizontal transfer of ecologically important traits. Annu. Rev. Entomol. 55, 247–266 (2010).

    PubMed  CAS  Google Scholar 

  152. Degnan, P. H., Yu, Y., Sisneros, N., Wing, R. A. & Moran, N. A. Hamiltonella defensa, genome evolution of protective bacterial endosymbiont from pathogenic ancestors. Proc. Natl Acad. Sci. USA 106, 9063–9068 (2009).

    PubMed  PubMed Central  CAS  Google Scholar 

  153. Rouïl, J., Jousselin, E., Coeur d’acier, A., Cruaud, C. & Manzano-Marín, A. The protector within: comparative genomics of APSE phages across aphids reveals rampant recombination and diverse toxin arsenals. Genome Biol. Evol. 12, 878–889 (2020).

    PubMed  PubMed Central  Google Scholar 

  154. Verster, K. I. et al. Horizontal transfer of bacterial cytolethal distending toxin B genes to insects. Mol. Biol. Evol. 36, 2105–2110 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  155. Perlmutter, J. I. et al. The phage gene wmk is a candidate for male killing by a bacterial endosymbiont. PLoS Pathog. 15, e1007936 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  156. Ren, F.-R. et al. Pantothenate mediates the coordination of whitefly and symbiont fitness. ISME J. 15, 1655–1667 (2021).

    PubMed  CAS  Google Scholar 

  157. Ren, F.-R. et al. Biotin provisioning by horizontally transferred genes from bacteria confers animal fitness benefits. ISME J. 14, 2542–2553 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  158. Manzano-Marín, A. et al. Serial horizontal transfer of vitamin-biosynthetic genes enables the establishment of new nutritional symbionts in aphids’ di-symbiotic systems. ISME J. 14, 259–273 (2020).

    Google Scholar 

  159. Bomar, L., Maltz, M., Colston, S. & Graf, J. Directed culturing of microorganisms using metatranscriptomics. mBio 2, e00012-11 (2011).

    PubMed  PubMed Central  Google Scholar 

  160. Browne, H. P. et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533, 543–546 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  161. Patel, V. et al. Cultivation-assisted genome of Candidatus Fukatsuia symbiotica; the enigmatic ‘X-type’ symbiont of aphids. Genome Biol. Evol. 11, 3510–3522 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  162. Kendra, C. G., Keller, C. M., Bruna, R. E. & Pontes, M. H. Conjugal DNA transfer in Sodalis glossinidius, a maternally inherited symbiont of tsetse flies. mSphere 5, e00864-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  163. Keller, C. M., Kendra, C. G., Bruna, R. E., Craft, D. & Pontes, M. H. DNA transduction in Sodalis species: implications for the genetic modification of uncultured endosymbionts of insects. mSphere 6, e01331–20 (2021).

    PubMed  PubMed Central  CAS  Google Scholar 

  164. Favia, G. et al. Bacteria of the genus Asaia stably associate with Anopheles stephensi, an Asian malarial mosquito vector. Proc. Natl Acad. Sci. USA 104, 9047–9051 (2007).

    PubMed  PubMed Central  CAS  Google Scholar 

  165. Nadal-Jimenez, P. et al. Genetic manipulation allows in vivo tracking of the life cycle of the son-killer symbiont, Arsenophonus nasoniae, and reveals patterns of host invasion, tropism and pathology. Environ. Microbiol. 21, 3172–3182 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  166. Rubin, B. E. et al. Targeted genome editing of bacteria within microbial communities. bioRxiv https://doi.org/10.1101/2020.07.17.209189 (2020).

    Article  Google Scholar 

  167. Ronda, C., Chen, S. P., Cabral, V., Yaung, S. J. & Wang, H. H. Metagenomic engineering of the mammalian gut microbiome in situ. Nat. Methods 16, 167–170 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  168. Wiles, T. J. et al. Modernized tools for streamlined genetic manipulation and comparative study of wild and diverse Proteobacterial lineages. mBio 9, e01877-18 (2018).

    PubMed  PubMed Central  Google Scholar 

  169. Leonard, S. P. et al. Genetic engineering of bee gut microbiome bacteria with a toolkit for modular assembly of broad-host-range plasmids. ACS Synth. Biol. 7, 1279–1290 (2018).

    PubMed  PubMed Central  CAS  Google Scholar 

  170. Visick, K. L., Hodge-Hanson, K. M., Tischler, A. H., Bennett, A. K. & Mastrodomenico, V. Tools for rapid genetic engineering of Vibrio fischeri. Appl. Environ. Microbiol. 84, e00850-18 (2018).

    PubMed  PubMed Central  Google Scholar 

  171. McLean, A. H. C. et al. Multiple phenotypes conferred by a single insect symbiont are independent. Proc. Biol. Sci. 287, 20200562 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  172. Moran, N. A. & Yun, Y. Experimental replacement of an obligate insect symbiont. Proc. Natl Acad. Sci. USA 112, 2093–2096 (2015).

    PubMed  PubMed Central  CAS  Google Scholar 

  173. Gong, J.-T. et al. Stable introduction of plant-virus-inhibiting Wolbachia into planthoppers for rice protection. Curr. Biol. 30, 4837–4845.e5 (2020).

    PubMed  CAS  Google Scholar 

  174. Ross, P. A., Turelli, M. & Hoffmann, A. A. Evolutionary ecology of Wolbachia releases for disease control. Annu. Rev. Genet. 53, 93–116 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  175. Crawford, J. E. et al. Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations. Nat. Biotechnol. 38, 482–492 (2020).

    PubMed  CAS  Google Scholar 

  176. Riglar, D. T. et al. Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nat. Biotechnol. 35, 653–658 (2017).

    PubMed  PubMed Central  CAS  Google Scholar 

  177. Isabella, V. M. et al. Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. Nat. Biotechnol. 36, 857–864 (2018).

    PubMed  CAS  Google Scholar 

  178. Praveschotinunt, P. et al. Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut. Nat. Commun. 10, 5580 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  179. Wang, S. et al. Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria. Science 357, 1399–1402 (2017).

    PubMed  CAS  Google Scholar 

  180. Leonard, S. P. et al. Engineered symbionts activate honey bee immunity and limit pathogens. Science 367, 573–576 (2020).

    PubMed  PubMed Central  CAS  Google Scholar 

  181. Belcaid, M. et al. Symbiotic organs shaped by distinct modes of genome evolution in cephalopods. Proc. Natl Acad. Sci. USA 116, 3030–3035 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  182. Douglas, A. E. Housing microbial symbionts: evolutionary origins and diversification of symbiotic organs in animals. Philos. Trans. R. Soc. Lond. B Biol. Sci. 375, 20190603 (2020).

    PubMed  PubMed Central  Google Scholar 

  183. Li, Y., Park, H., Smith, T. E. & Moran, N. A. Gene family evolution in the pea aphid based on chromosome-level genome assembly. Mol. Biol. Evol. 36, 2143–2156 (2019).

    PubMed  PubMed Central  CAS  Google Scholar 

  184. Misof, B. et al. Phylogenomics resolves the timing and pattern of insect evolution. Science 346, 763–767 (2014).

    PubMed  CAS  Google Scholar 

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Acknowledgements

We thank H. Ochman for critical comments. Funding came from NIH R35GM131738 to NAM and a University of Texas Austin Provost’s Graduate Excellence fellowship to J.P.

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    Julie Perreau & Nancy A. Moran

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Supplementary information

Glossary

Symbiont transmission mode

The route by which symbionts are acquired each generation, ranging from strictly vertical (parent-to-offspring) to strictly horizontal (between non-parent–offspring pairs of hosts or between hosts and non-host sources). Mixed-mode transmission combines vertical and horizontal modes.

Genetic recombination

The exchange of genetic material between organisms. Recombination can be roughly classified as homologous recombination, which involves the exchange of related sequences, and non-homologous recombination, in which unrelated sequences are inserted into the genome as in the case of horizontal gene transfer.

Purifying selection

The removal of deleterious alleles by natural selection. Also referred to as negative selection. This is the most common form of selection, as mutations are more often deleterious than beneficial.

dN/dS

The ratio of non-synonymous substitutions (that is, those that change the amino acid sequence) per non-synonymous site (dN) to the number of synonymous substitutions (that is, those that do not change the amino acid sequence) per synonymous site (dS), used to determine the mode and strength of selection that has acted on genetic sequences.

Bacteriocytes

Host cells that are specialized for housing bacterial symbionts.

Heterologous expression

Expression of a gene in an alternative, genetically tractable host.

Trophallaxis

The exchange of food through an oral-to-oral or faecal-to-oral transmission route, commonly performed by members of the same community.

Axenic culture

The culture of a single microbial strain, in the absence of additional strains or hosts, in laboratory culture media.

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Perreau, J., Moran, N.A. Genetic innovations in animal–microbe symbioses. Nat Rev Genet 23, 23–39 (2022). https://doi.org/10.1038/s41576-021-00395-z

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