Host genomic variation shapes gut microbiome diversity in threespine
stickleback fish
Abstract
Variation among host-associated microbiomes is well documented across
species, populations, and individuals. Understanding relationships
between host-genetic and microbial variation is important for predicting
coevolutionary dynamics between hosts and their microbiota and is also
biomedically relevant to understanding why some humans are more
susceptible to chronic disorders like Inflammatory Bowel Diseases (IBD).
Unfortunately, the relative contributions of host genetics and the
environment to microbiome variation have been difficult to study. Human
research shows that genetic variation influences microbiome differences
but confounding environmental effects cannot be controlled
experimentally. Isogenic laboratory models can be used in controlled
environments but often focus on large-effect mutations and do not
recapitulate genetic variation observed in nature. Thus, although
important factors impacting the microbiome have been identified, few
studies have tested for the direct influence of natural host-genetic
variation on microbiome differences within a controlled environment. To
address this, we performed a common garden experiment using laboratory
lines of genetically divergent populations of threespine stickleback
fish - an outbred model organism commonly used for determining the
genetic basis of complex traits in the context of natural genetic
variation. Using germ-free derivation of divergent lines and hybrids
between them in this experimental framework, we detected a clear,
positive association between stickleback genetic dissimilarity and
microbiome dissimilarity. With RAD-seq data we identified regions of the
genome that contributed most significantly to this relationship.
Importantly, we also highlight that heritable morphological traits like
body size -when correlated with microbiome composition - need
consideration in future host-associated microbiome studies.