How invading jumping genes are thwarted

image credit: sciencedaily.com

Since Carnegie Institution's Barbara McClintock received her Nobel Prize on her discovery of jumping genes in 1983, we have learned that almost half of our DNA is made up of jumping genes -- called transposons. Given their ability of jumping around the genome in developing sperm and egg cells, their invasion triggers DNA damage and mutations. This often leads to animal sterility or even death, threatening species survival. The high abundance of jumping genes implies that organisms have survived millions, if not billions, of transposon invasions. However, little is known about where this adaptability comes from.

Now, a team of Carnegie researchers has discovered that, upon jumping gene invasion, reproductive stem cells boost production of non-coding RNA elements (piRNA) that suppress their activity and activates a DNA repair process allowing for normal egg development. The results are published in the November 1, 2018, issue of Developmental Cell.

The researchers studied jumping genes in the fruit fly Drosophila melanogaster -- a classic model to study jumping genes in developing sperm and egg cells. To set up a powerful system studying jumping gene adaptation, the researchers needed a tool to control their activity. It has been known for four decades that environmental temperature influences the severity of sterility in the fruit fly upon jumping gene invasion. At temperatures of 77 degrees F (25 degrees C) offspring have sterile ovaries, while at 64 degrees F (18 degrees C) offspring have fully developed and fertile ovaries.

'Cellular memory' of DNA damage in oocyte quality control

image credit: myfuturebaby.com

Females are born with a finite number of eggs that are steadily depleted throughout their lifetime. This reserve of eggs is selected from a much larger pool of millions of precursor cells, or oocytes, that form during fetal life. So there is a substantial amount of quality control during the process of forming an egg cell, or ovum, that weeds out all but the highest quality cells. New research from Neil Hunter's laboratory at UC Davis reveals the surprising way that this critical oocyte quality control process works.

Previous research in the Hunter lab showed that a gene called Rnf212 is required for chromosomes to undergo crossing over during the early stages of oocyte development. The researchers were surprised to find a new, late function for Rnf212 in the oocyte selection process. The results are published Sept. 27 in the journal Molecular Cell.

During oocyte quality control, a decision is made whether each oocyte should continue and join the reserve of eggs, or undergo apoptosis -- cellular death.

"We almost stumbled upon this role in oocyte quality control when Joe (Huanyu Qiao, joint first author) first noticed that the Rnf212 mutants had more oocytes in their ovaries," said Hunter, professor of Microbiology and Molecular Genetics and an Investigator of the Howard Hughes Medical Institute. Hunter is senior author on the paper.

Nurses' care of young mothers leaves traces in babies' DNA

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In a study, recently published in Translational Psychiatry, a McGill-led team of scientists have been able to demonstrate long-lasting but subtle effects, at a genetic level, on the offspring of young mothers who took part in a nurse visitation program for vulnerable first time moms. This is the longest-running study of its kind, and the first to look at how positive psychosocial interventions can leave an epigenetic trace.

Advice from nurses for mothers-at-risk

In 1977 young, pregnant, first-time mothers from low-income families in a town in upstate New York were assigned to one of two groups. One group of women was offered free assessments of child development and transportation to a clinic for their medical appointments. The other women could have up to two years of home visits from trained nurses from the Nurse Family Partnership program who shared practical information about child rearing and family planning. The number of visits varied from one woman to another, from as few as six visits to as many as 30, but the impact of these visits can be seen today.

There were 400 women enrolled in the initial study. Now, over 30 years later, close to half of their offspring took part in a follow-up study. Their numbers were fairly evenly divided between the offspring of women who had received visits from nurses (99 people) and those who had not (89 people). One part of the current study involved responding to an online questionnaire about mental health diagnoses of illnesses ranging from major depression to substance abuse.

Here, the researchers saw little difference between the offspring of the women who had received visits from nurses and those who had not. (Though because only half of the initial group took part in the follow-up study, the researchers suggest that it is possible that this was a self-selecting group who were more likely to have experienced abuse along with psychiatric disorders.)

A small but important step along the way

But it was when the researchers took blood samples to gain a picture of what was going on at a genetic level, that they saw a significant though subtle difference between the two groups.

"Initially we ran just a small subgroup of participants and we found evidence of an association between a psychosocial intervention that ended at the age of two and changes in DNA methylation, a modification to DNA that can change the way that certain genes are expressed," says Kieran O'Donnell, the lead author who is based at McGill University. "So, I held my breath waiting for the analysis on the full cohort, and then we saw that the results held."

DNA methylation is a process whereby groups of atoms (known as methyl groups) are added to DNA molecules to change the activity of a DNA segment without changing the sequence itself. Though the field of epigenetics is still relatively young and it is difficult for researchers to say exactly what the implications are of these epigenetic modifications, they believe that with further work, this information will prove useful for precision medicine efforts for children and adolescents.

Michael Meaney, the senior author who is based at the Douglas Hospital Research Centre adds, "It's fascinating to see that interventions that started while a child was in the womb and stopped by age two can leave traces that last a lifetime. This research shows that early intervention programs have an effect. But more longitudinal studies of this kind will need to be done before we can see how this information will prove clinically useful in the treatment of child and adolescent mental health. For the time being, all we can say is that family intervention programs have left their mark, quite literally." 

Source: https://medicalxpress.com/news/2018-05-nurses-young-mothers-babies-dna.html

Twelve DNA areas 'linked with the age at which we have our first child and family size'

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"Researchers have identified 12 specific areas of the DNA sequence that are robustly related with the age at which we have our first child, and the total number of children we have during the course of our life. 

The study, led by the University of Oxford, working together with the Universities of Groningen, The Netherlands and Uppsala, Sweden, includes an analysis of 62 datasets with information from 238,064 men and women for age at first birth, and almost 330,000 men and women for the number of children. 

Until now, reproductive behaviour was thought to be mainly linked to personal choices or social circumstances and environmental factors. However, this new research shows that genetic variants can be isolated and that there is also a biological basis for reproductive behaviour. The paper is co-authored by over 250 sociologists, biologists, and geneticists from institutions worldwide, and has been published in the journal, Nature Genetics.

Lead author Professor Melinda Mills, from the Department of Sociology and Nuffield College at the University of Oxford, comments: 'For the first time, we now know where to find the DNA areas linked to reproductive behaviour. For example, we found that women with DNA variants for postponing parenthood also have bits of DNA code associated with later onset of menstruation and later menopause. 

One day it may be possible to use this information so doctors can answer the important question: "How late can you wait?" based on the DNA variants. It is important to put this into perspective, however, as having a child still strongly depends on many social and environmental factors that will always play a bigger role in whether or when we have babies.'..."

Learn more:

https://www.sciencedaily.com/releases/2016/11/161101104311.htm

Children with 3-way DNA are healthy

credit: AP Photo/Richard Drew

"More than 15 years ago, 17 babies were born after an experimental infertility treatment that gave them DNA from three people: Mom, Dad and an egg donor.

Now researchers have checked up on how the babies are doing as teenagers. The preliminary verdict: The kids are all right.

With no sign of unusual health problems and excellent grades in school at ages 13 to 18, these children are "doing well," said embryologist Jacques Cohen of the Institute for Reproductive Medicine & Science at Saint Barnabas in Livingston, New Jersey, where the treatment was done.

That includes Emma Foster, 17, of Red Bank, New Jersey. "I turned out normal," Foster said in an interview Tuesday. A cheerleader since age 10, she is now looking at colleges and thinking of majoring in engineering.

The infertility procedure is no longer performed. But the study of the children is timely because just last month, the first baby was born from a different procedure that also mixed genetic material from three people. That technique is aimed not at infertility but at preventing the child from inheriting harmful genes from the mother. Critics are concerned about its long-term safety..."

Learn more:

http://medicalxpress.com/news/2016-10-kids-children-way-dna-healthy.html

Researchers storing information securely in DNA

via techinsider.io

"Experiments at CERN's Large Hadron Collider generate 15 million gigabytes of data per year. That is a lot of digital data to inscribe on hard drives or beam up to the "cloud."
George Bachand, a Sandia National Laboratories bioengineer at the Center for Integrated Nanotechnologies, is exploring a better, more permanent method for encrypting and storing sensitive data: DNA. Compared to digital and analog information storage, DNA is more compact and durable and never becomes obsolete. Readable DNA was extracted from the 600,000-year-old remains of a horse found in the Yukon.

Tape- and disk-based data storage degrades and can become obsolete, requiring rewriting every decade or so. Cloud- or server-based storage requires a vast amount of electricity; in 2011 Google's server farms used enough electricity to power 200,000 U.S. homes. Furthermore, old-school methods require lots and lots of space. IBM estimated 1,000 gigabytes of information in book form would take up seven miles of bookshelves. In fact, Sandia recently completed a 15,000-square-foot building to store 35,000 boxes of inactive records and archival documents.

"Historically, the national laboratories and the U.S. government have a lot of highly secure information that they need to store long-term. I see this as a potentially robust way of storing classified information in the future to preserve it for multiple generations," said Bachand. "The key is how do you go from text to DNA and do that in a way that is safe and secure..."

Learn more:
http://phys.org/news/2016-07-dna.html

Male mitochondrial DNA found to self-destruct after arrival in embryo

via wanderinginthestacks.wordpress.com

"A team of researchers with members from Taiwan, the U.S., China and Japan has found that mitochondrial DNA from sperm that makes its way into an embryo begins to self-destruct before autophagosomes in the cytoplasm can reach it. In their paper published in the journal Science, the researchers describe their study involving the close monitoring of male mitochondrial DNA activity immediately after an embryo has been fertilized and as it is subsequently destroyed—they also offer some theories regarding why this occurs.

Over the past half-century, scientists have learned that some amount of DNA exists outside of the cell nucleus and inside mitochondria. They have also found that only the mitochondrial DNA from the mother is passed on to the child during reproduction—the mitochondrial DNA from the father is destroyed before it can have an impact. These discoveries have led to other studies looking to better understand why this occurs.

In this new effort, the researchers used electron microscopy to watch the process in a type of roundworm. In so doing, they discovered that the male mitochondria in sperm actually began to break down before being cut up by autophagosomes in the cytoplasm—an extra guarantee, it seemed, to ensure that the male DNA would not be allowed to become part of the embryo's DNA. 

Looking more closely, the researchers found that the existence of the cps-6 gene caused expression of an enzyme that initiated the self-destruction process—they also found that the enzyme was able to both break down the membrane protecting the DNA and then to cause the DNA itself to break down..."

Learn more:

http://medicalxpress.com/news/2016-06-male-mitochondrial-dna-self-destruct-embryo.html

Scientists unlock X-Files DNA mystery

"Scientists have unlocked a crucial part of the mystery as to how our DNA can replicate and repair itself - something which is essential for all life forms.

The new research, conducted by leading scientists at the University of Sheffield, has revealed how branched DNA molecules are removed from the iconic double-helical structure -a process which scientists have been looking to unlock for over 20 years.

Jon Sayers, Professor of Functional Genomics at the University of Sheffield and lead author of the study, said: "Branched DNA features in several episodes of the X-Files as Agent Scully suspects aliens inserted it in her blood.

"In reality, far from being of alien origin, branched DNA is formed every day in our bodies. It happens every time our cells divide. These branches are essential intermediates formed during the process of copying our DNA."

The interdisciplinary team from the University's Departments of Infection, Immunity and Cardiovascular Disease, and Molecular Biology and Biotechnology, captured never-before-seen snapshots of the molecular events in incredible detail. They show how Flap EndoNuclease enzymes (FENs) trim branched DNA molecules after cells have divided.

The scientists found the FEN threads the free end of the branch through a hole in the enzyme before sliding along to the trunk where it acts like a pair of molecular secateurs, trimming the branch and restoring the iconic double-helix..."

Learn more:

http://phys.org/news/2016-06-truth-scientists-x-files-dna-mystery.html