Interactions between chromosomal and nonchromosomal elements reveal missing heritability.
The measurement of any nonchromosomal genetic contribution to the heritability of a trait is often confounded by the inability to control both the chromosomal and nonchromosomal information in a population. We have designed a unique system in yeast where we can control both sources of information so that the phenotype of a single chromosomal polymorphism can be measured in the presence of different cytoplasmic elements. With this system, we have shown that both the source of the mitochondrial genome and the presence or absence of a dsRNA virus influence the phenotype of chromosomal variants that affect the growth of yeast. Moreover, by considering this nonchromosomal information that is passed from parent to offspring and by allowing chromosomal and nonchromosomal information to exhibit nonadditive interactions, we are able to account for much of the heritability of growth traits. Taken together, our results highlight the importance of including all sources of heritable information in genetic studies and suggest a possible avenue of attack for finding additional missing heritability.
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
Matthew D
MD
Edwards
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
Anna
A
Symbor-Nagrabska
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
Lindsey
L
Dollard
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;Whitehead Institute for Biomedical Research, Cambridge, MA 02142;Broad Institute of MIT and Harvard University, Cambridge, MA 02142; andDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, Cambridge, MA 02138 gifford@mit.edu gfink@wi.mit.edu.
David K
DK
Gifford
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;Broad Institute of MIT and Harvard University, Cambridge, MA 02142; and gifford@mit.edu gfink@wi.mit.edu.
Gerald R
GR
Fink
D000704:Analysis of Variance; D002875:Chromosomes / Q000235:genetics*; D019295:Computational Biology; D005111:Extrachromosomal Inheritance / Q000235:genetics*; D005787:Gene Frequency; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000628:therapy*; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015003:Yeasts / Q000235:genetics* / Q000254:growth & development
extrachromosomal; genetic interactions; nonlinear model