Expanding the brain: Research identifies more than 40 new imprinted genes

Expanding the brain: Research identifies more than 40 new imprinted genes
Led by Catherine Dulac, the Higgins Professor of Molecular and Cellular Biology, a team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced. The findings, described in a recent paper in eLife, reveal how genomic imprinting can dramatically expand biological diversity, and could have important implications for understanding the brain. Credit: File photo by Kris Snibbe/Harvard Staff Photographer

It's among the cornerstones of biology: All mammals inherit two copies ― one from their mother, the other from their father—of every gene, in part to act as a backstop against genetic problems. If a gene is damaged or malfunctions, its double can pick up the slack.

When it comes to inheritance, however, not all genes are created equal.

Led by Catherine Dulac, the Higgins Professor of Molecular and Cellular Biology, a team of researchers has identified more than 40 new "imprinted" genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced. The findings, described in a recent paper in eLife, reveal how can dramatically expand biological diversity, and could have important implications for understanding the brain.

"We looked at a single brain area—the cerebellum—in a very rigorous way, and found 115 imprinted genes, more than 40 of which were brand-new," Dulac said. "That is a 30 percent increase in the number of known imprinted genes in the mouse, which is significant, but the other important idea this paper explores is the notion that these imprinted genes provide a way for the diversity of the brain to flourish. In addition to the diversity in our genetic sequence, the question of who are we inheriting these genes from adds to the diversity we see across a population."

The notion of genomic imprinting emerged in the late 1980s, when researchers began manipulating mouse embryos in the moments after fertilization. When sperm and egg fuse to form a zygote, Dulac explained, each temporarily forms a separate pronucleus—one carrying genetic information from the mother, the other from the father. These later fuse to become the nucleus of the embryo.

When researchers began manipulating the pronuclei by replacing the paternal version with a second maternal copy, or implanting two paternal copies, embryos failed to develop.

"That was very surprising," Dulac said. "At the time, it was believed that you simply needed two copies of each gene, but this suggested that some genes are expressed only from one of the two parental genomes, and you need both to give rise to a full-blown organism."

After first focusing on the cerebellum, Dulac's team expanded its analysis to the entire brain.

"In the second part of the paper, we looked at how these imprinted genes are distributed across the brain, and between brain and non-brain tissue. The big surprise is that we found a very large subset of imprinted genes that are only imprinted in the brain, and some only in a subset of brain regions."

The surprise came in part because scientists have long believed that if a gene is imprinted in one tissue, it is likely imprinted through most of the organism's tissues, including through the brain.

"But we don't think that's the case," Dulac said. "We think there's some very interesting regulation of imprinting from the brain to non-brain tissue, and even from one brain region to another."

While genomic imprinting is often thought to silence one copy of a gene, the study showed that many aren't completely silenced, but rather show a bias toward one copy.

"So there may be 70 percent expression from the maternal allele, and 30 percent from the paternal," Dulac said. "It's not all on or all off."

To understand whether these biases have biological significance, Dulac and colleagues targeted a gene called Bcl-X, which, in the adult cerebellum, is expressed 60 percent from the paternal genome and 40 percent from the maternal, and helps prevent cell death.

"Our question is, 'Does the brain care about that bias?'" Dulac said. "If it doesn't we could remove either copy of the gene, and it shouldn't matter. But if that bias ― even though it's not particularly strong—is important, when we remove the more highly expressed copy of the gene, we should see a different phenotype emerge.

"When we did this, the results were spectacular. When we removed the paternal copy, we obtained mice with brains that were 15 to 20 percent smaller than mice in which we removed the maternal copy or mice which had both copies."

Importantly, Dulac said, tests showed that, in the cortex, were more affected by the change.

Many researchers believe that the ratio between excitatory and inhibitory neurons plays a key role in development, Dulac said, and that an imbalance between the two types could be related to a number of disorders, including autism and schizophrenia.


Explore further

Taking the 'mute' off silenced gene may be answer to Angelman syndrome

Provided by Harvard University

This story is published courtesy of the Harvard Gazette, Harvard University's official newspaper. For additional university news, visit Harvard.edu.

Citation: Expanding the brain: Research identifies more than 40 new imprinted genes (2015, July 30) retrieved 21 May 2019 from https://medicalxpress.com/news/2015-07-brain-imprinted-genes.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
221 shares

Feedback to editors

User comments

JVK
Jul 31, 2015
Related research article Santoro S, Dulac C. 2012. The activity-dependent histone variant H2BE modulates the life span of olfactory neurons. eLife 1:e00070. doi: 10.7554/eLife.00070

The experience-dependent variant links what is known about the biophysically constrained chemistry of nutrient dependent RNA-mediated protein folding to imprinted cell types via amino acid substitutions that determine cell type differences in all cell types of all individuals of all organisms.

The physiology of reproduction links germ cells to somatic cells and to morphological and behavioral differences in the sexes during thermodynamic cycles of protein biosynthesis and degradation, which are perturbed by viruses. The complexity of virus-driven entropic elasticity, which is modulated by the anti-entropic epigenetic effects of nutrient-dependent microRNAs, has been placed into the context of mutations and evolution by biologically uninformed theorists.

Dulac is not one of them.

JVK
Jul 31, 2015
PZ Myers is a biologically uninformed theorist who attacked Nathaniel Jeanson, a Harvard-educated Ph.D

See: A first-hand report of Nathaniel Jeanson's lecture in Boston http://scienceblo...nathani/

Excerpt: "As I told Catherine Dulac, his former dept. head at Harvard, it was an hour-long spectacle of misinformation, half-truths and what appeared to be deliberate obfuscation."

The link from Jeanson's claims to the reports from Dulac on experience-dependent receptor-mediated differences in imprinted genes, cell type differences, and morphological and behavioral phenotypes can now be placed into the context of virus-driven genomic entropy.

Entropy is prevented by the nutrient-dependent de novo creation of olfactory receptor genes. RNA-mediated gene duplication and nutrient-dependent RNA-mediated fixation of amino acid substitutions links viruses and mutations to olfactory receptor gene loss.

JVK
Jul 31, 2015
The light-induced de novo creation of amino acids links the creationist perspective "Let there be light" to nutrient-dependent RNA-mediated amino acid substitutions that differentiate cell types via the experience-dependent de novo creation of olfactory receptor genes and virus perturbed protein folding that links mutations to the loss of olfactory receptor genes that are no longer needed.

The accumulation of viral microRNAs continues if it is not prevented by nutrient-dependent microRNAs that control the finely-tuned microRNA/messenger RNA balance and RNA-mediated cell type differentiation. Neo-Darwinian theorists placed that balance into the context of mutations and evolution.

They may have been stopped from presenting any more pseudoscientific nonsense by Eugene Koonin's claim: "The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis..."

JVK
Aug 01, 2015
See also: http://phys.org/n...ior.html

What made biologically uniformed human ethologists, like Jay R. Feierman, think that the sense of smell in birds was any less important to RNA-mediated cell type differentiation and ecological niche construction than it is to all other invertebrates and vertebrates?

Had they never heard the term "bird flu" or did they simply attribute the virus-driven problem to mutations in the context of ridiculous theories about evolution?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more