Abstract
The brain is one of the most prominent examples for structural and functional differences between the left and right half of the body. For handedness and language lateralization, the most widely investigated behavioral phenotypes, only a small fraction of phenotypic variance has been explained by molecular genetic studies. Due to environmental factors presumably also playing a role in their ontogenesis and based on first molecular evidence, it has been suggested that functional hemispheric asymmetries are partly under epigenetic control. This review article aims to elucidate the molecular factors underlying hemispheric asymmetries and their association with inner organ asymmetries. While we previously suggested that epigenetic mechanisms might partly account for the missing heritability of handedness, this article extends this idea by suggesting possible alternatives for transgenerational transmission of epigenetic states that do not require germ line epigenetic transmission. This is in line with a multifactorial model of hemispheric asymmetries, integrating genetic, environmental, and epigenetic influencing factors in their ontogenesis.
Highlights
In 1866, German zoologist Ernst Haeckel introduced promorphology – the science of an organism’s external form – and proposed symmetry as a fundamental criterion for classifying organisms (Haeckel, 1866)
We previously (Schmitz et al, 2017b) suggested that epigenetic mechanisms might partly account for the large gap between heritability estimates for handedness from twin and adoption studies of up to 0.66 (Risch and Pringle, 1985) and the small variance explained by molecular genetic studies (Eriksson et al, 2010; Armour et al, 2014), known as the missing heritability problem (Maher, 2008)
As germ line epigenetic inheritance is highly controversial in humans (Ambeskovic et al, 2017b), we suggest an alternative mechanism by which epigenetic mechanisms might account for the missing heritability of functional hemispheric asymmetries
Summary
In 1866, German zoologist Ernst Haeckel introduced promorphology – the science of an organism’s external form – and proposed symmetry as a fundamental criterion for classifying organisms (Haeckel, 1866). Bilateral symmetry is frequently broken by either the position of non-paired internal organs in one body half (e.g., the left-sided stomach and the right-sided liver) or by anatomical differences between the left and right half of paired internal organs. The human lungs are constituted of two lobes on the left and three lobes on the right side. Based on these observations, humans and other vertebrates have been described as “pseudobilateral” (see Figure 1; Levin, 2005). The brain is one of the most striking examples for structural and functional differences between the left and right half of the body. We recently reviewed the evidence for environmental factors in handedness ontogenesis and suggested that functional
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