Differentially methylated obligatory epialleles modulate context-dependent <i>LAM</i> gene expression in the honeybee <i>Apis mellifera</i>

<p>Differential intragenic methylation in social insects has been hailed as a prime mover of environmentally driven organismal plasticity and even as evidence for genomic imprinting. However, very little experimental work has been done to test these ideas and to prove the validity of such claims. Here we analyze in detail differentially methylated obligatory epialleles of a conserved gene encoding lysosomal α-mannosidase (<i>AmLAM</i>) in the honeybee. We combined genotyping of progenies derived from colonies founded by single drone inseminated queens, ultra-deep allele-specific bisulfite DNA sequencing, and gene expression to reveal how sequence variants, DNA methylation, and transcription interrelate. We show that both methylated and non-methylated states of <i>AmLAM</i> follow Mendelian inheritance patterns and are strongly influenced by polymorphic changes in DNA. Increased methylation of a given allele correlates with higher levels of context-dependent <i>AmLAM</i> expression and appears to affect the transcription of an antisense long noncoding RNA. No evidence of allelic imbalance or imprinting involved in this process has been found. Our data suggest that by generating alternate methylation states that affect gene expression, sequence variants provide organisms with a high level of epigenetic flexibility that can be used to select appropriate responses in various contexts. This study represents the first effort to integrate DNA sequence variants, gene expression, and methylation in a social insect to advance our understanding of their relationships in the context of causality.</p

Descriptive characteristics of participants by gender.

<p>Descriptive characteristics of participants by gender.</p

Correlation coefficients between VAT, body fat, anthropometric indices, blood pressure, blood lipids and HOMA-IR (males and females combined).

<p>Correlation coefficients between VAT, body fat, anthropometric indices, blood pressure, blood lipids and HOMA-IR (males and females combined).</p

Receiver operating characteristics of VAT for identifying triglyceride level ≥150 mg/dL in males (left) and females (right).

<p>P refers to logistic regression model.</p

Receiver operating characteristics of VAT for identifying waist circumference ≥94 cm in males (left) and ≥80 cm in females (right).

<p>P refers to logistic regression model.</p

AUC values and cut-off points for VAT volume by gender.

<p>AUC values and cut-off points for VAT volume by gender.</p

Functional trends of DEGs classified according to the Biological Process terms defined by GO consortium

<p><b>Copyright information:</b></p><p>Taken from "Molecular determinants of caste differentiation in the highly eusocial honeybee "</p><p>http://www.biomedcentral.com/1471-213X/7/70</p><p>BMC Developmental Biology 2007;7():70-70.</p><p>Published online 18 Jun 2007</p><p>PMCID:PMC1929063.</p><p></p> (A) Developing workers up-regulate more developmental genes than queens in all studied larval instars. Physiometabolic genes are always more up-regulated than developmental genes (B) Juvenile hormone (JH) treatment induces a queen-like gene expression profile. Left panel: up-regulated genes in L4 queens/workers. Right panel: up-regulated genes in L4 Control/JH-treated workers. The proportion of Physiometabolic and Localization genes is higher in normal queens and JH-treated workers, whereas more Developmental genes are up-regulated in normal and in Control workers