Question

Explain what is meant by the thrifty gene hypothesis (also known as the Barker's hypothesis or foetal programming) and describe the epigenetic processes involved in foetal programming.

Please give a detailed answer. Add supportive equations or flow diagrams if possible.

Thank you.

Answer 1

The thrifty gene hypothesis is a hypothesis proposed by a geneticist James V Neel for explaining the increased number of diabetes patients in modern society. It also tried explaining the obesity as well. It was found that the genes, called thrifty genes that promoted efficient fat deposition might have been advantageous to human populations who were agriculturalists and hunter-gatherers. Also the thrifty genotypes would help them survive during a time of food scarcity. But in modern society there is a transition of lifestyle and constant abundance of food that promotes fat deposition by thrifty genes. This is found disadvantageous and resulted in more obese and diabetic people. The physical inactivity and diets that are high in saturated fats and carbohydrates increased the insulin resistance. Finally scientists Hales and Barker state that poor nutrition including the nutrition in prenatal period is also associated with the risk of metabolic syndromes like obesity, diabetes, hypertension etc.

Epigenetic programming involves mitotically heritable modifications to the chromatin structure that can govern the patterns of expression of genes. The phenotype of an individual is inherited by the genetic code of parents and manifestation of this genetic code can be modified during fetal development. This is called fetal epigenetic programming. In this mechanism the regulation of gene expression is done at pre-transcription levels, during transcription, cis-acting element binding and post transcription. The most common methods are DNA methylation and histone modification although other mechanisms like genomic imprinting, chromatin remodeling etc. are available. In DNA methylation a methyl group (CH3) is added to 5-methylcystosine in the DNA at the cis-acting element. This causes changes in binding of trans-acting factor thus regulated the gene expression. Another mechanism called histone modification is by the addition of an acetyl group (COCH3) .This can have an impact in the gene expression by the altering of chromatin structure. The acetylation in different positions is likely to function in differing ways.Apart from these, miRNAs plays role in post-transcriptional gene regulation. These are subtypes of small, noncoding RNA, which are capable of base pairing with mRNA.They regulate gene expression during development by suppressing their expression in a sequence-specific manner.