Open AccessBehavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms
Author(s) -
Emma J. Mitchell,
Shifra Liba Klein,
Kimon V. Argyropoulos,
Abhijeet Sharma,
Robin B. Chan,
Judit Gal Toth,
Luendreo Barboza,
Charlotte C. Bavley,
Analı́a Bortolozzi,
Qiuying Chen,
Bingfang Liu,
Joanne Ingenito,
Willie Mark,
Jarrod A Dudakov,
Steven S. Gross,
Gilberto di Paolo,
Francesc Artigas,
Marcel van den Brink,
Miklós Tóth
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms11492
Subject(s) - biology , epigenetics , genetics , offspring , germline mosaicism , germline , phenotype , somatic cell , penetrance , dna methylation , pleiotropy , quantitative trait locus , trait , gene , evolutionary biology , pregnancy , gene expression , computer science , programming language
Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.