Within the last century, researchers’ understanding of genetics has undergone a profound transformation.

Genes, regions of DNA that are largely responsible for our physical characteristics, were considered unchanging under the original model of genetics pioneered by biologist Gregor Mendel in 1865. That is, genes were thought to be largely unaffected by a person’s environment.

The emergence of the field of epigenetics in 1942 shattered this notion.

Epigenetics refers to shifts in gene expression that occur without changes to the DNA sequence. Some epigenetic changes are an aspect of cell function, such as those associated with aging.

However, environmental factors also affect the functions of genes, meaning people’s behaviors affect their genetics. For instance, identical twins develop from a single fertilized egg, and as a result, they share the same genetic makeup. However, as the twins age, their appearances may differ due to distinct environmental exposures. One twin may eat a healthy balanced diet, whereas the other may eat an unhealthy diet, resulting in differences in the expression of their genes that play a role in obesity, helping the former twin have lower body fat percentage.

People don’t have much control over some of these factors, such as air quality. Other factors, though, are more in a person’s control: physical activity, smoking, stress, drug use and exposure to pollution, such as that coming from plastics, pesticides and burning fossil fuels, including car exhaust.

Another factor is nutrition, which has given rise to the subfield of nutritional epigenetics. This discipline is concerned with the notions that “you are what you eat” – and “you are what your grandmother ate.” In short, nutritional epigenetics is the study of how your diet, and the diet of your parents and grandparents, affects your genes. As the dietary choices a person makes today affects the genetics of their future children, epigenetics may provide motivation for making better dietary choices.

Two of us work in the epigenetics field. The other studies how diet and lifestyle choices can help keep people healthy. Our research team is comprised of fathers, so our work in this field only enhances our already intimate familiarity with the transformative power of parenthood.

A story of famine

The roots of nutritional epigenetics research can be traced back to a poignant chapter in history – the Dutch Hunger Winter in the final stages of World War II.

During the Nazi occupation of the Netherlands, the population was forced to live on rations of 400 to 800 kilocalories per day, a far cry from the typical 2,000-kilocalorie diet used as a standard by the Food and Drug Administration. As a result, some 20,000 people died and 4.5 million were malnourished.

Studies found that the famine caused epigentic changes to a gene called IGF2 that is related to growth and development. Those changes suppressed muscle growth in both the children and grandchildren of pregnant women who endured the famine. For these subsequent generations, that suppression led to an increased risk of obesity, heart disease, diabetes and low birth weight.

These findings marked a pivotal moment in epigenetics research – and clearly demonstrated that environmental factors, such as famine, can lead to epigenetic changes in offspring that may have serious implications for their health.

The role of the mother’s diet

Until this groundbreaking work, most researchers believed epigenetic changes couldn’t be passed down from one generation to the next. Rather, researchers thought epigenetic changes could occur with early-life exposures, such as during gestation – a highly vulnerable period of development. So initial nutritional epigenetic research focused on dietary intake during pregnancy.

The findings from the Dutch Hunger Winter were later supported by animal studies, which allow researchers to control how animals are bred, which can help control for background variables. Another advantage for researchers is that the rats and sheep used in these studies reproduce more quickly than people, allowing for faster results. In addition, researchers can fully control animals’ diets throughout their entire lifespan, allowing for specific aspects of diet to be manipulated and examined. Together, these factors allow researchers to better investigate epigenetic changes in animals than in people.

In one study, researchers exposed pregnant female rats to a commonly used fungicide called vinclozolin. In response to this exposure, the first generation born showed decreased ability to produce sperm, leading to increased male infertility. Critically, these effects, like those of the famine, were passed to subsequent generations.

As monumental as these works are for shaping nutritional epigenetics, they neglected other periods of development and completely ignored the role of fathers in the epigenetic legacy of their offspring. However, a more recent study in sheep showed that a paternal diet supplemented with the amino acid methionine given from birth to weaning affected the growth and reproductive traits of the next three generations. Methionine is an essential amino acid involved in DNA methylation, an example of an epigenetic change.

Healthy choices for generations to come

These studies underscore the enduring impact parents’ diets have on their children and grandchildren. They also serve as a powerful motivator for would-be parents and current parents to make more healthy dietary choices, as the dietary choices parents make affect their children’s diets.

Meeting with a nutrition professional, such as a registered dietitian, can provide evidence-based recommendations for making practical dietary changes for individuals and families.

There are still many unknowns about how diet affects and influences our genes. What research is starting to show about nutritional epigenetics is a powerful and compelling reason to consider making lifestyle changes.

There are many things researchers already know about the Western Diet, which is what many Americans eat. A Western Diet is high in saturated fats, sodium and added sugar, but low in fiber; not surprisingly, Western diets are associated with negative health outcomes, such as obesity, type 2 diabetes, cardiovascular disease and some cancers.

A good place to start is to eat more whole, unprocessed foods, particularly fruits, vegetables and whole grains, and fewer processed or convenience foods – that includes fast food, chips, cookies and candy, ready-to-cook meals, frozen pizzas, canned soups and sweetened beverages.

These dietary changes are well known for their health benefits and are described in the 2020-2025 Dietary Guidelines for Americans and by the American Heart Association.

Many people find it difficult to embrace a lifestyle change, particularly when it involves food. Motivation is a key factor for making these changes. Luckily, this is where family and friends can help – they exert a profound influence on lifestyle decisions.

However, on a broader, societal level, food security – meaning people’s ability to access and afford healthy food – should be a critical priority for governments, food producers and distributors, and nonprofit groups. Lack of food security is associated with epigenetic changes that have been linked to negative health outcomes such as diabetes, obesity and depression.

Through relatively simple lifestyle modifications, people can significantly and measurably influence the genes of their children and grandchildren. So when you pass up a bag a chips – and choose fruit or a veggie instead – keep in mind: It’s not just for you, but for the generations to come.

(Authors:Nathaniel Johnson, Assistant Professor of Nutrition and Dietetics, University of North Dakota; Hasan Khatib, Associate Chair and Professor of Genetics and Epigenetics, University of Wisconsin-Madison, and Thomas D. Crenshaw, Professor of Animal and Dairy Sciences, University of Wisconsin-Madison)

(Disclosure Statement:Nathaniel Johnson receives funding from the United States Department of Agriculture and the National Institutes of Health. He has previously received funding through the National Science Foundation, the National Cattlemen’s Beef Association, and the North Dakota Beef Checkoff. Hasan Khatib receives funding no. 2023-67015-39527 from the USDA National Institute of Food and Agriculture. Thomas D Crenshaw receives funding from Hatch Multi-State Research Formula Funds; USDA/Natl. Institute of Food and Agriculture; DHHS, PHS, National Institutes of Health)

This article is republished from The Conversation under a Creative Commons license. Read the original article.
 

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The Y chromosome is a never-ending source of fascination (particularly to men) because it bears genes that determine maleness and make sperm. It’s also small and seriously weird; it carries few genes and is full of junk DNA that makes it horrendous to sequence.

However, new “long-read” sequencing techniques have finally provided a reliable sequence from one end of the Y to the other. The paper describing this Herculean effort has been published in Nature.

The findings provide a solid base to explore how genes for sex and sperm work, how the Y chromosome evolved, and whether – as predicted – it will disappear in a few million years.

Making baby boys

We have known for about 60 years that specialised chromosomes determine birth sex in humans and other mammals. Females have a pair of X chromosomes, whereas males have a single X and a much smaller Y chromosome.

Also Read | Men are slowly losing their Y chromosome, but a new sex gene discovery in spiny rats brings hope for humanity

The Y chromosome is male-determining because it bears a gene called SRY, which directs the development of a ridge of cells into a testis in the embryo. The embryonic testes make male hormones, and these hormones direct the development of male features in a baby boy.

Without a Y chromosome and a SRY gene, the same ridge of cells develops into an ovary in XX embryos. Female hormones then direct the development of female features in the baby girl.

A DNA junkyard

The Y chromosome is very different from X and the 22 other chromosomes of the human genome. It is smaller and bears few genes (only 27 compared to about 1,000 on the X).

These include SRY, a few genes required to make sperm, and several genes that seem to be critical for life – many of which have partners on the X. Many Y genes (including the sperm genes RBMY and DAZ) are present in multiple copies. Some occur in weird loops in which the sequence is inverted and genetic accidents that duplicate or delete genes are common.

Also Read | The role of the Y chromosome in cancer outcomes studied 

The Y also has a lot of DNA sequences that don’t seem to contribute to traits. This “junk DNA” is comprised of highly repetitive sequences that derive from bits and pieces of old viruses, dead genes and very simple runs of a few bases repeated over and over.

This last DNA class occupies big chunks of the Y that literally glow in the dark; you can see it down the microscope because it preferentially binds fluorescent dyes.

Why the Y is weird

Why is the Y like this? Blame evolution.

We have a lot of evidence that 150 million years ago the X and Y were just a pair of ordinary chromosomes (they still are in birds and platypuses). There were two copies – one from each parent – as there are for all chromosomes.

Then SRY evolved (from an ancient gene with another function) on one of these two chromosomes, defining a new proto-Y. This proto-Y was forever confined to a testis, by definition, and subject to a barrage of mutations as a result of a lot of cell division and little repair.

Also Read | Male-centric medicine is affecting women’s health 

The proto-Y degenerated fast, losing about 10 active genes per million years, reducing the number from its original 1,000 to just 27. A small “pseudoautosomal” region at one end retains its original form and is identical to its erstwhile partner, the X.

There has been great debate about whether this degradation continues, because at this rate the whole human Y would disappear in a few million years (as it already has in some rodents).

Sequencing Y was a nightmare

The first draft of the human genome was completed in 1999. Since then, scientists have managed to sequence all the ordinary chromosomes, including the X, with just a few gaps.

They’ve done this using short-read sequencing, which involves chopping the DNA into little bits of a hundred or so bases and reassembling them like a jigsaw.

But it’s only recently that new technology has allowed sequencing of bases along individual long DNA molecules, producing long-reads of thousands of bases. These longer reads are easier to distinguish and can therefore be assembled more easily, handling the confusing repetitions and loops of the Y chromosome.

Also Read | Male fertility crisis: what environmental contaminants have got to do with it 

The Y is the last human chromosome to have been sequenced end-to-end, or T2T (telomere-to-telomere). Even with long-read technology, assembling the DNA bits was often ambiguous, and researchers had to make several attempts at difficult regions – particularly the highly repetitive region.

So what’s new on the Y?

Spoiler alert – the Y turns out to be just as weird as we expected from decades of gene mapping and the previous sequencing.

A few new genes have been discovered, but these are extra copies of genes that were already known to exist in multiple copies. The border of the pseudoautosomal region (which is shared with the X) has been pushed a bit further toward the tip of the Y chromosome.

We now know the structure of the centromere (a region of the chromosome that pulls copies apart when the cell divides), and have a complete readout of the complex mixture of repetitive sequences in the fluorescent end of the Y.

But perhaps the most important outcome is how useful the findings will be for scientists all over the world.

Some groups will now examine the details of Y genes. They will look for sequences that might control how SRY and the sperm genes are expressed, and to see whether genes that have X partners have retained the same functions or evolved new ones.

Others will closely examine the repeated sequences to determine where and how they originated, and why they were amplified. Many groups will also analyse the Y chromosomes of men from different corners of the world to detect signs of degeneration, or recent evolution of function.

It’s a new era for the poor old Y.