The differential view of genotype-phenotype relationships

Abstract

An integrative view of diversity and singularity in the living world requires a better understanding of the intricate link between genotypes and phenotypes. Here we re-emphasize the old standpoint that the genotype-phenotype (GP) relationship is best viewed as a connection between two differences, one at the genetic level and one at the phenotypic level. As of today, predominant thinking in biology research is that multiple genes interact with multiple environmental variables (such as abiotic factors, culture, or symbionts) to produce the phenotype. Often, the problem of linking genotypes and phenotypes is framed in terms of genotype and phenotype maps, and such graphical representations implicitly bring us away from the differential view of GP relationships. Here we show that the differential view of GP relationships is a useful explanatory framework in the context of pervasive pleiotropy, epistasis, and environmental effects. In such cases, it is relevant to view GP relationships as differences embedded into differences. Thinking in terms of differences clarifies the comparison between environmental and genetic effects on phenotypes and helps to further understand the connection between genotypes and phenotypes.

Keywords: GxE; GxG; complex trait; genetics; genotype; phenotype.

FIGURE 1

Schematic representations of GP links. (A) Traditional representation in classical genetic reductionism. (B) Integrative view of developmental biology. (C) Scheme of the experimental approach in genetics. (D) Scheme of the experimental approach in evolutionary genetics. (E) One example of taxonomically robust GP relationship: SLC45A2 and intraspecific differences in pigmentation in tigers and in chickens. GP relationships are indicated by dashed lines in panels (D–E).

FIGURE 2

Three current graphical representations of GP maps. (A) The early version of the GP map proposed by Lewontin (1974a). (B) A GP map where each point represents a single individual (Houle et al., 2010; Gjuvsland et al., 2013; Salazar-Ciudad and Marín-Riera, 2013). (C) The relationships between traits and genes, as depicted by Wagner (1996). See text for details.

FIGURE 3

Evolution of light-colored beach mice is caused by several mutations with distinct pigmentation effects in the Agouti locus. The dark and light phenotypes can be decomposed into four phenotypic traits, which are associated with different single nucleotide polymorphisms (SNPs, colored dots) located in the Agouti gene. Only SNPs with inferred selection coefficient of the light allele higher than 0.1 are shown. Coding exons are represented as dark boxes and untranslated exons as white boxes. Adapted from Linnen et al. (2013).

FIGURE 4

Gene-by-environment (GxE) and GxG interactions. (A) The npr-1 coding mutation affects nematode aggregation behavior at 21% oxygen levels but not at 10% (Andersen et al., 2014). (B) The Mc1R coding mutation affects mouse body pigmentation in presence of dominant light alleles of Agouti but not in an Agouti homozygous background for the recessive dark allele (Steiner et al., 2007).

FIGURE 5

Environment–phenotype relationship vs. GP relationship for sex determination in turtles. (A) In some species, the temperature during embryonic development determines the sex of the adult. (B) In others, sex is determined by sex chromosomes.

FIGURE 6

The environment-phenotype relationship and GP relationship perspectives for wing length polymorphism in the beetle Calathus melanocephalus. (A) Under the environment-phenotype relationship perspective, a change in food conditions is associated with a change in wing size, but only in a homozygous background for the recessive allele (l) of the wing size locus. (B) Under the GP relationship perspective, a genetic change at the wing size locus is associated with a change in wing size, but only in good food conditions.