New Scientist - USA (2020-08-01)

44 | New Scientist | 1 August 2020

divided 50:50 between two Xs, that seems

to change over the life course; they can skew.

If there’s injury in the skin, for example,

and the skin is healing, you can have one

population of healing cells taking over.

It seems that when their function within

the healing is complete, it eventually goes

back down to 50:50. Men just have to cope

with the genes on their one X.

How might this process affect other parts

of the body?

Everywhere we have looked in the body, there

can be skewing. In a woman’s body, if the cells

in the heart that carry her father’s X can

survive lack of oxygen during a heart attack,

it will be that population that survives. We

see that benefit in many parts of the body,

including the liver and the kidneys. The toxic

compounds that we can’t withstand or get rid

of will kill our cells. The cells with the X genes

that can better withstand those toxins

outcompete the others.

How does it affect resistance to infections?

Our first understanding of this was with the

immune system because it’s easy to tap – you

just take out some blood. The X is rich in

immune-related genes. If a population of a

certain kind of immune cell does a better job

using genes from the X from the father, that

cell population will shift, so you might have

80 or 90 per cent of those cells using the X

from the father.

And you believe that’s why women tend

to cope better with the coronavirus?

Yes. There’s an important group of genes

on the X that encode a receptor called toll-

like receptor 7 (TLR7), which helps cells

recognise single-stranded RNA viruses,

such as the coronavirus. Women have two

populations of immune cells, each one

using a different version of TLR7 to recognise

coronavirus. Another interesting layer is

that the coronavirus uses a protein on

our cells called ACE2 to enter our cells.

The gene for ACE2 just happens to be on

the X chromosome. Right from the get-go,

females have an advantage.

What about behavioural reasons proposed

for the female survival advantage in covid-19?

The first explanation I heard from some of

my colleagues was that males don’t wash

their hands – which is nonsense when you

see data that says more women are infected

than men, and yet more men die. The other

thing was that everyone rushed to say it’s

smoking. About 50 per cent of males in

China smoke, and about 3 per cent of females

smoke. But when you start looking at other

countries – in the US, for example, the rate

for male smoking is about 15 per cent,

for females 13 per cent – you still see the

same pattern of higher male deaths.

We rush to use behaviour as an

explanation because we are told that the

biggest differences between the sexes is

behaviour. When I started my career, I was

told that the reason we see so many more

females at the end of life is because more

men smoke and drink, and they take risks.

All those things may be true, but it’s ignoring

the fact that more girls make it to their first

birthday. Girls who have asphyxia at birth

do better cognitively as well. It’s hard to

argue that the sexes’ behaviours are different

in the incubator.

But two X chromosomes don’t always confer

an advantage. Don’t women have higher rates

of autoimmune conditions, where the immune

system mistakenly attacks healthy cells?

Yes, the female immune system is more

aggressive than the male immune system.

Part of that’s because female hormones

called oestrogens stimulate the immune

system, while in males, testosterone inhibits

it. But what’s interesting is that even before

puberty, autoimmunity is still higher in

females. The explanation could be the

X chromosome.

In both sexes, in the fetus, thyroid

gland immune cells usually go through an

“educational process”, where if immune cells

recognise other cells from the person’s own

body, the immune cells self-destruct. That’s

to make sure that once the baby is born,

autoimmunity doesn’t happen. The process

works relatively well in males. But females,

who have two genetically different cell

populations, are more likely to fail at

destroying all the self-recognising cells.

Coming out of the thymus, female immune

cells are more likely to recognise their own

cells as “foreign”. That sets up the perfect

storm for autoimmunity.

Lifelong effects: More

females than males

survive infancy,

while women also

tend to live longer

than men and are less

vulnerable to covid-19

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