Genes in mitochondria have disproportionate effect
Plant and animal cells carry most of their genes on chromosomes in the nucleus. But in Arabidopsis, they also contain a small number of genes in the mitochondria outside the nucleus — which affect chemicals found in its leaves equal in proportion to nuclear genes.
New research from the University of California, Davis, shows that the tiny proportion of a cell's DNA that is located outside the cell nucleus has a disproportionately large effect on a cell's metabolism. The work, with the model plant Arabidopsis, may have implications for future treatments for inherited diseases in humans.
The influence of genes outside the nucleus was known to an earlier generation of field ecologists and crop breeders, said Dan Kliebenstein, professor in the UC Davis Department of Plant Sciences and Genome Center and senior author on the paper published Oct. 8 in the online journal eLife. This is the first time that the effect has been quantified with genomic research, he said.
Bindu Joseph, a postdoctoral researcher in Kliebenstein's lab, and Kliebenstein studied how variation in 25,000 nuclear genes and 200 mitochondrial genes affected the levels of thousands of individual chemicals, or metabolites, in leaf tissue from 316 Arabidopsis plants.
The scientists found that 80 percent of the chemicals in leaf tissue were directly affected by variations in mitochodrial genes — about the same proportion that were affected by variation among the much larger number of nuclear genes.
There were also indirect effects, where mitochondrial genes regulated the activity of nuclear genes that in turn affected metabolism.
"At first it's surprising, but at another level you almost expect it," Kliebenstein said. "These organelles produce energy and sugar for cells, so they are very important."
Similar effects could also occur in mammalian cells, Kliebenstein said.
This has implications for in vitro fertilization therapies aimed at preventing diseases caused by faulty mitochondria being passed from mother to child.
The British government recently proposed draft regulations for "three-parent embryos," created by taking a the nucleus from a fertilized egg and putting it into an egg cell from a third donor with its own set of mitochondria.
The technique has so far only been tested in animals.
"From what we can see in plants, there might be an issue, but it needs testing," Kliebenstein said.
Large population surveys that aim to link conditions such as obesity to specific genes should also take more account of organellar genes, he said.
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.
- See more at: http://elife.elifesciences.org/content/2/e00776#sthash.roFFYk7H.dpuf
Co-authors on the paper are graduate student Jason Corwin and project scientists Baohua Li and Suzi Atwell.
The work was supported by the National Science Foundation.
Original press release: http://news.ucdavis.edu/search/news_detail.lasso?id=10743