Model selection emphasises the importance of non-chromosomal information in genetic studies

Abstract

Ever since the case of the missing heritability was highlighted some years ago, scientists have been investigating various possible explanations for the issue. However, none of these explanations include non-chromosomal genetic information. Here we describe explicitly how chromosomal and non-chromosomal modifiers collectively influence the heritability of a trait, in this case, the growth rate of yeast. Our results show that the non-chromosomal contribution can be large, adding another dimension to the estimation of heritability. We also discovered, combining the strength of LASSO with model selection, that the interaction of chromosomal and non-chromosomal information is essential in describing phenotypes.

Fig 1. Non-chromosomal information enhances the fraction of phenotypic variance explained.

Three linear models with different complexity are applied to measure the fraction of phenotypic variance. The first model (simple) includes only the gene deletion status (red), the second model (additive) considers the gene deletion status and non-chromosomal elements (orange), and finally the third model (interaction) includes both chromosomal and non-chromosomal elements as well as their interaction (yellow). The fraction of phenotypic variance is thereby approximated by the average coefficient of determination ($R_a^2$) of 1000 randomly sampled sub-sets. Aside from the control MCM22 and the gene deletion PHO88(non-killer) experiment, model accuracy increases considerably when non-chromosomal information is included and much more when the interaction is taken into account.