Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives

Abstract

Thought to be directly and uniquely dependent from genotypes, the ontogeny of individual phenotypes is much more complicated. Individual genetics, environmental exposures, and their interaction are the three main determinants of individual’s phenotype. This picture has been further complicated a decade ago when the Lamarckian theory of acquired inheritance has been rekindled with the discovery of epigenetic inheritance, according to which acquired phenotypes can be transmitted through fertilization and affect phenotypes across generations. The results of Genome-Wide Association Studies have also highlighted a big degree of missing heritability in genetics and have provided hints that not only acquired phenotypes, but also individual’s genotypes affect phenotypes intergenerationally through indirect genetic effects. Here, we review available examples of indirect genetic effects in mammals, what is known of the underlying molecular mechanisms and their potential impact for our understanding of missing heritability, phenotypic variation. and individual disease risk.

Early survival in Atlantic salmon is associated with parental genotypes at loci linked to timing of maturation

“…Finally, the survival effects associated with six6 and vgll3 loci are in opposite directions to each other with respect to their effect on maturation timing: while the vgll3 L allele (the allele linked to later age at maturity) appears to be associated with higher offspring survival, it is the early maturation allele ( six6 E ) that positively influences offspring survival in the six6 region, which necessitates that variation in both loci is accounted for when formulating predictions. Put together, our results highlight the complexity related to predicting the evolutionary dynamics of maturation age in Atlantic salmon, and potentially in other taxa where indirect genetic effects have been found (e.g., Bonduriansky and Day 2009; Tomar and Teperino 2020, Wolf et al 1998). The observed genetic correlation, however, suggests that a physiological, mechanistic link exists between genetic polymorphisms in the life-history loci and early survival.…”

The Legacy of Parental Obesity: Mechanisms of Non-Genetic Transmission and Reversibility

“…We have provided an overview of the intergenerational consequences of parental obesity that are induced or mediated bona fide by epigenetic mechanisms. Lately, studies have highlighted an equally important role of parental modifiers of offspring health beyond the epigenome (for a review, see [ 120 , 121 ]). In the following section, we briefly review the known facts about the relevance of the oocyte environment, the seminal fluid, and the parental microbiota composition in the intergenerational transmission of non-genetic information and phenotype programming ( Figure 1 ).…”

Introduction to Mammalian Genome Special Issue: Epigenetics

“…In addition to environmental factors like nutrition and stress, also genetic alterations in the parental generation can affect phenotypes of wildtype offspring. Tomar and Teperino in this issue review such examples in mammals and discuss the current data in support of this type of indirect genetic inheritance (Tomar and Teperino 2020 , vol. 31, pp.…”