Understanding genome to phenotype linkages has been greatly enabled by genomic sequencing. However, most genome analysis is typically confined to the nuclear genome. We conducted a metabolomic QTL analysis on a reciprocal RIL population structured to examine how variation in the organelle genomes affects phenotypic variation. This showed that the cytoplasmic variation had effects similar to, if not larger than, the largest individual nuclear locus. Inclusion of cytoplasmic variation into the genetic model greatly increased the explained phenotypic variation. Cytoplasmic genetic variation was a central hub in the epistatic network controlling the plant metabolome. This epistatic influence manifested such that the cytoplasmic background could alter or hide pairwise epistasis between nuclear loci. Thus, cytoplasmic genetic variation plays a central role in controlling natural variation in metabolomic networks. This suggests that cytoplasmic genomes must be included in any future analysis of natural variation.
The vast majority of genes in plant and animal cells are located on chromosomes within the nucleus. However, cells also contain a small number of genes outside the nucleus in cellular organelles such as the mitochondria, which generate energy, and the chloroplasts, which carry out photosynthesis. All these non-nuclear genes comprise the organellar genome.
When trying to explain how variation in genes leads to differences in the characteristics of animals and plants, geneticists have historically paid most attention to the genes inside the nucleus. However, more recent work has shown that variation in the organellar genome can also contribute to differences between individuals, although the relative contribution of organellar genes versus nuclear genes remains unclear.
Now, Joseph et al. have performed the first large-scale analysis of how variation in the organellar genome affects the characteristics (or phenotype) of the plant model organism, Arabidopsis. The study examined the degree to which variation in each of roughly 13,000 nuclear genes and 200 organellar genes affected the levels of thousands of metabolites inside cells.
This metabolomics analysis revealed that variation in the organellar genome contributed to variation in the levels of more than 80% of the metabolites studied. Organellar genes also helped to regulate the effect of nuclear genes. This combination of direct and indirect influences helps to explain how a small number of organellar genes can have a disproportionately large effect on phenotype.
The work of Joseph et al. suggests that the role of the organellar genome has been significantly underestimated to date, and that geneticists should consider variation in both the nuclear and organellar genome when attempting to determine how genes affect phenotype.