Genome-wide association studies across environmental and genetic contexts reveal complex genetic architecture of symbiotic extended phenotypes

Abstract

A goal of modern biology is to develop the genotype-phenotype (G-P) map, a predictive understanding of how genomic information generates the organismal trait variation that forms the basis of both natural and managed communities. As microbiome research advances, however, it has become clear that many of these traits are governed by genetic variation encoded not only by the host's own genome, but also by the genomes of myriad cryptic symbionts. Thus many ecologically-important traits are likely symbiotic extended phenotypes, and this recognition adds even more complexity to our conceptions of the G-P map. In model symbioses such as the legume-rhizobium mutualism, host growth and fitness often depend on genetic variation in symbiont partner quality, and our ability to manipulate host and symbiont genotype combinations, combined with increasingly precise sequencing and mapping approaches, provides an opportunity to characterize the genetic nature of these symbiotic extended phenotypes. Here we use naturally-occurring genetic variation in 191 strains of the nitrogen-fixing symbiont Ensifer meliloti in four mapping experiments to study the genomic architecture of symbiotic partner quality within and across environmental contexts and host genotypes. We demonstrate the quantitative genetic nature of symbiotic extended phenotypes, including extensive context-dependency in both the identity and functions of symbiont loci that control host growth. We additionally resolve a core set of universal loci from populations in the native range that are likely important in all or most environments, and thus, serve as excellent targets both for genetic engineering and future coevolutionary studies of symbiosis.

Phenotypic and genomic signatures of interspecies cooperation and conflict in naturally-occurring isolates of a model plant symbiont

“…At the genomic-level, distinct variants underlying rhizobium fitness pleiotropy on each host genotype suggests that the genetic mechanisms (i.e., genes, pathways, metabolic processes) governing the relationship between fitness proxies are largely non-overlapping when rhizobia interact with different hosts. Such host genotype-dependent shifts in the rhizobium genetic architecture of these symbiotic extended phenotypes is supported by transcriptomics studies of G x G interactions (33, 44) and GWAS revealing distinct sets of candidate genes in different host backgrounds (34, 46). Similar genetic variation exists in hosts (86) and undoubtedly interacts with the variants we identify here, thus, should be accounted for if we are to build a reliable G→P map.…”

“…Such LD results from multiple, non-mutually exclusive factors including epistatic interactions among individual variants that render discordant variants effectively neutral, and/or past selection favouring allelic combinations that increase both host and symbiont fitness (and disfavours discordant combinations; 79, 80). Overall, these findings highlight the polygenic nature of partner quality variation in nature -where the collective action of individual mutations, their additive and nonadditive effects (46), and a history of selection shapes the trait variation currently present in natural populations (81,82).…”

“…Full details are provided in Batstone et al (46), and SI Methods . Briefly, we conducted two separate experiments in Sept and Nov 2018, one for each M. truncatula line, DZA and A17, respectively.…”

“…Legumes house rhizobia within specialized root nodules and supply them with photosynthate, while rhizobia within the nodules convert atmospheric N to a plant-usable form, resulting in a beneficial exchange of resources. Key traits of this symbiosis, such as plant biomass and nodule number, are known to be influenced by variants in the genomes of both host and microbes, as well as the epistatic interactions between them (Genotype-by-Genotype or G x G interactions; e.g., 4,34,38,[43][44][45][46], making this symbiosis an excellent model for understanding mutualistic coevolution.…”

Genomes within genomes: nested symbiosis and its implications for plant evolution

“…Rather than extensions of the microbial genome, MGEs instead represent distinct genomes nested within microbes, similar to how microbes are distinct from their plant hosts. Loci within MGEs not only have the potential to influence microbial traits, including antibiotic resistance (Förster et al ., 2015), but also plant traits via their interaction with microbes, including plant growth (Batstone et al ., 2021b). Therefore, genetic variation within MGEs, in addition to plants and microbes, must be explicitly accounted for if we want to understand how plant traits evolve (Box 1).…”