The Y chromosome is disappearing – so what will happen to men?

Disclosure statement

Darren Griffin has current collaborative grants with JSR Genetics and Topigs Norsvin. Including BBSRC
and Innovate UK funding. Enhancing oocyte quality to improve assisted reproduction in peri-pubertal pigs
and cattle (BBSRC) - About to start. £335,000 Technology Strategy Board (BBSRC - Inovate UK). Pig IVF
and genetics: A route to global sustainability.
The Y chromosome may be a symbol of masculinity, but it is becoming increasingly clear that it is anything
but strong and enduring. Although it carries the “master switch” gene, SRY, that determines whether an
embryo will develop as male (XY) or female (XX), it contains very few other genes and is the only
chromosome not necessary for life. Women, after all, manage just fine without one.
What’s more, the Y chromosome has degenerated rapidly, leaving females with two perfectly normal X
chromosomes, but males with an X and a shrivelled Y. If the same rate of degeneration continues, the Y
chromosome has just 4.6m years left before it disappears completely. This may sound like a long time, but it
isn’t when you consider that life has existed on Earth for 3.5 billion years.

The Y chromosome hasn’t always been like this. If we rewind the clock to 166m years ago, to the very first
mammals, the story was completely different. The early “proto-Y” chromosome was originally the same size
as the X chromosome and contained all the same genes. However, Y chromosomes have a fundamental
flaw. Unlike all other chromosomes, which we have two copies of in each of our cells, Y chromosomes are
only ever present as a single copy, passed from fathers to their sons.

This means that genes on the Y chromosome cannot undergo genetic recombination, the “shuffling” of
genes that occurs in each generation which helps to eliminate damaging gene mutations. Deprived of the
benefits of recombination, Y chromosomal genes degenerate over time and are eventually lost from the
genome.

Chromosome Y in red, next to the much larger X chromosome. National Human Genome Research Institute
Despite this, recent research has shown that the Y chromosome has developed some pretty convincing
mechanisms to “put the brakes on”, slowing the rate of gene loss to a possible standstill.
For example, a recent Danish study, published in PLoS Genetics, sequenced portions of the Y chromosome
from 62 different men and found that it is prone to large scale structural rearrangements allowing “gene
amplification” – the acquisition of multiple copies of genes that promote healthy sperm function and
mitigate gene loss.

The study also showed that the Y chromosome has developed unusual structures called “palindromes”
(DNA sequences that read the same forwards as backwards – like the word “kayak”), which protect it from
further degradation. They recorded a high rate of “gene conversion events” within the palindromic
sequences on the Y chromosome – this is basically a “copy and paste” process that allows damaged genes to
be repaired using an undamaged back-up copy as a template.

Looking to other species (Y chromosomes exist in mammals and some other species), a growing body of
evidence indicates that Y-chromosome gene amplification is a general principle across the board. These
amplified genes play critical roles in sperm production and (at least in rodents) in regulating offspring sex
ratio. Writing in Molecular Biology and Evolution recently, researchers give evidence that this increase in
gene copy number in mice is a result of natural selection.

On the question of whether the Y chromosome will actually disappear, the scientific community, like the UK
at the moment, is currently dividedinto the “leavers” and the “remainers”. The latter group argues that its
defence mechanisms do a great job and have rescued the Y chromosome. But the leavers say that all they
are doing is allowing the Y chromosome to cling on by its fingernails, before eventually dropping off the
cliff. The debate therefore continues.

Mole voles have no Y chromosomes. wikipedia

A leading proponent of the leave argument, Jenny Graves from La Trobe University in Australia, claims
that, if you take a long-term perspective, the Y chromosomes are inevitably doomed – even if they
sometimes hold on a bit longer than expected. In a 2016 paper, she points out that Japanese spiny rats and
mole voles have lost their Y chromosomes entirely – and argues that the processes of genes being lost or
created on the Y chromosome inevitably lead to fertility problems. This in turn can ultimately drive the
formation of entirely new species.

The demise of men?

As we argue in a chapter in a new e-book, even if the Y chromosome in humans does disappear, it does not
necessarily mean that males themselves are on their way out. Even in the species that have actually lost
their Y chromosomes completely, males and females are both still necessary for reproduction.

In these cases, the SRY “master switch” gene that determines genetic maleness has moved to a different
chromosome, meaning that these species produce males without needing a Y chromosome. However, the
new sex-determining chromosome – the one that SRY moves on to – should then start the process of
degeneration all over again due to the same lack of recombination that doomed their previous Y
chromosome.

However, the interesting thing about humans is that while the Y chromosome is needed for normal human
reproduction, many of the genes it carries are not necessary if you use assisted reproduction techniques.
This means that genetic engineering may soon be able to replace the gene function of the Y chromosome,
allowing same-sex female couples or infertile men to conceive. However, even if it became possible for
everybody to conceive in this way, it seems highly unlikely that fertile humans would just stop reproducing
naturally.

Although this is an interesting and hotly debated area of genetic research, there is little need to worry. We
don’t even know whether the Y chromosome will disappear at all. And, as we’ve shown, even if it does, we
will most likely continue to need men so that normal reproduction can continue.

Indeed, the prospect of a “farm animal” type system where a few “lucky” males are selected to father the
majority of our children is certainly not on the horizon. In any event, there will be far more pressing
concerns over the next 4.6m years.

When a mom feels depressed, her baby’s cells might feel it too
January 22, 2018 6.28am EST
At just 18 months old, young children can show biological evidence of added stress.
Disclosure statement

Benjamin W. Nelson received funding from the Mind and Life Institute to conduct this research.
Heidemarie Laurent received funding from the Society for Research on Child Development to conduct this
study.
Nick Allen does not work for, consult, own shares in or receive funding from any company or organization
that would benefit from this article, and has disclosed no relevant affiliations beyond their academic
appointment.

An estimated 1 in 9 women experience symptoms of postpartum depression. These symptoms – including

mood swings, fatigue and reduced interest in activities – can make it difficult for mothers to bond with their
newborns.

Early relationships between mothers and their infants can influence health across the lifespan, for better or
worse. For example, adults who report more household dysfunction and abuse during their childhood
are more likely to suffer disease as adults. Those with healthy and supportive relationships during early
life are better at handling stress and regulating their emotions.

However, scientists do not completely understand how these environments get “under the skin” to shape
health. Our latest paper, published in November, shows a possible link between increasing depression
symptoms in mothers and cellular damage in their infants.

Telomeres and health

How does stress affect our cells? One area of burgeoning research focuses on telomeres.

The 46 human chromosomes are shown in blue, with the telomeres appearing as white pinpoints
Telomeres are caps at the end of our DNA that protect chromosomes. They’re analogous to the plastic tips
at the end of shoelaces that keep laces from unraveling. In essence, these plastic caps keep laces functional.
The same can be said of your telomeres.

Since the length of telomeres is affected by our genetics and age, they’re sometimes thought of as part of a
“biological clock” that reflects the age of our cells. As telomeres shorten over time, people are more likely to
experience a host of negative health outcomes, such as cardiovascular disease, dementia, diabetes, cancer,
obesity and even death.

Interestingly, telomeres can degrade more quickly when a person suffers from psychological stress. When
we experience stress, our bodies release a hormone called cortisol, which influences our emotional
responses as well as our energy metabolism, learning and memory. This may be one mechanism that
connects psychological stress to telomere length and ultimately physical health. Cells that are exposed to
cortisol have shorter telomeres and less telomerase, which is the enzyme responsible for maintaining the
ends of telomeres.

This process may explain how psychological stress is converted to biological “wear and tear.”
Indeed, adolescents with depressed mothershave heightened cortisol stress responses and shorter
telomeres than their peers, even when the adolescents themselves are not depressed.
Our study
We examined whether increasing maternal depressive symptoms affected infant stress and later cell health.

Infancy is a sensitive period, when individuals are strongly influenced by their environment. One way to
study how early stress may influence health is to look at how infants respond to their parents’ stress.
Studies suggest that infants exposed to maternal depression may be less likely to engage socially and
experience more negative emotion.

For our study we recruited 48 mothers with 12-week-old infants and followed these families until the
infants were 18 months old. At 6 and 12 months of age, the infants were brought to the lab to engage in
mildly stressful tasks. For example, in the “still face experiment,” mothers alternated between playing with
their infant and not reacting to their infant’s bids for attention. This can elicit stress in infants, as they rely
on their caregivers to not only feed them, but to also soothe their emotions.

An example of the ‘still face experiment.’

During each visit, we measured infants’ stress by collecting saliva samples to look at changes in cortisol. We
also collected information on how many depression symptoms mothers were feeling. Finally, when the
infants were 18 months of age, we brought the families back into our lab and collected saliva to measure the
length of the infant’s telomeres.

Worsening depression symptoms in mothers related to greater infant cortisol stress responses between 6
and 12 months of age. In addition, infants with higher cortisol stress responses were more likely to have
shorter telomeres at 18 months of age, indicating greater cellular wear and tear.

Better mental health

While these findings are preliminary and should be replicated with a larger group of infants, our results
highlight how patterns of health across the lifespan may be influenced in the first 18 months of life. This
early stress may put young children on track for the early onset of poor health outcomes.

The silver lining is that infancy is a sensitive developmental period, when humans are especially responsive
to their environments. Fostering positive experiences between infants and their mothers – as well as
providing affordable, scientifically supported treatment services for mothers experiencing depression – may
allow infants to move toward a healthier life trajectory.

In our view, these results show how important it is to fund effective maternal mental health treatment and
early childhood policies.