Genetic backgrounds and hidden trait complexity in natural populations

Abstract

Dissecting the genetic basis of natural phenotypic variation is a major goal in biology. We know that most traits are strongly heritable. However, their genetic architecture is a long-standing question, which is unfortunately confounded by the lack of complete knowledge of the genetic components as well as their phenotypic effect in a specific genetic background. Many genetic variants are known to affect phenotypes but the same functional variant can have a different effect on the phenotype in different individuals of the same species. Understanding the impact of genetic background on the expressivity of a given phenotype is essential because this effect complicates our ability to predict phenotype from genotype. Here, we briefly review recent progress on the exploration of the effect of genetic background and we discuss how a deeper characterization of the inheritance, expressivity and genetic interactions hidden behind the phenotypic landscape of natural variation could provide a better understanding of the relationship between genotype and phenotype.

Figure 1. Penetrance and expressivity of traits

In the case of a monogenic disease, all individual carrying the causal allele are expected to develop the same trait. However, in some cases, individuals with the causal allele do not express the expected phenotype, resulting in incomplete penetrance. For other traits, the phenotype will be expressed differentially in different individuals: some will develop more severe symptoms while others display milder symptoms thus representing phenotypic expressivity.

Figure 2. Phenotypic impact of the genetic background

A: An allele present in different genetic backgrounds results in the same phenotypic outcome at the organismal level. However, this does not mean that intermediate phenotypes such as molecular traits (e.g. gene expression level) will be the same. Every layer of intermediate phenotype acts as a lens that can deflect the phenotype in a specific way with the organism phenotype as the focal point of all these superimposed lenses. B: Some mutations, however, alter intermediate phenotypes and change the final organism phenotype.

Figure 3. Trait complexity acts as a continuum at the species level

When crossing a rare variant into multiple genetic backgrounds, the underlying genetic complexity of a trait can range from Mendelian or monogenic trait to complex. Genetic complexity underlying the trait can be assessed by looking at the offspring phenotypic distribution. A bimodal distribution following Mendelian ratios (2:2 for haploids and 3:1 for diploids) suggests a monogenic trait. Deviations from these ratios are signs of higher but intermediate level of complexity. Ultimately, a normal phenotypic distribution depicts a complex phenotype.