The Economist Asia - 24.02.2018

The EconomistFebruary 24th 2018 67

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1

W

HAT’S a gene? You might think biolo-

gists had worked that one out by

now. But the question is more slippery

than may at first appear. The conventional

answer is something like, “a piece ofDNA

that encodes the structure of a particular

protein”. Proteins so created run the body.

Genes, meanwhile, are passed on in sperm

and eggs to carry the whole process to the

next generation.

None of this is false. But it is now clear

that reality is more complex. Many genes, it

transpires, do not encode proteins. Instead,

they regulate which proteins are produced.

These newly discovered genes are sources

of small pieces ofRNA, known as micro-

RNAs. RNAis a molecule allied to DNA, and

is produced when DNAis read by an en-

zyme called RNApolymerase. If the DNAis

a protein-coding gene, the resultingRNA

acts as a messenger, taking the protein’s

plan to a place where proteins are made.

Micro-RNAs regulate this process by bind-

ing to the messengerRNA, making it inac-

tive. More micro-RNAmeans less of the

protein in question, and vice versa.

Often, this regulation is in response to

environmental stimuli such as stress. And

sometimes, the responses acquired in this

way seem to be passed down through the

generations, in apparent defiance of con-

ventional genetic theory. The best known

example in people comes from the Nether-

lands, which suffered famine in 1944, at the

tions on part of the male genital tract called

the epididymis. This is where sperm ma-

ture. Cells lining the epididymis constantly

discharge small, fluid-filled, membrane-

bound bubbles called vesicles. When Ms

Chan, working with mice, looked in detail

at these vesicles, she found that they con-

tained lots of micro-RNAs.

That was interesting. But she then went

on to do an experiment. Mice are easily

stressed. Simply putting new objects into

their living space is enough to induce sig-

nificant changes in their levels of stress

hormones. Stress a male in this way and

his offspring (of either sex) will react less to

stress than do the offspring of unstressed

males. That looks like intergenerational

epigenesis. It also makes evolutionary

sense, since it calibrates a mouse’s stress re-

sponse to the stressfulness of the environ-

ment—which is likely to be the same as that

of its father. To prove that this intergenera-

tional effect was caused by epididymal mi-

cro-RNAs, Ms Chan collected these mole-

cules and injected them into fertilised

mouse eggs. Those eggs, as she had hy-

pothesised they would, grew into less-

stress-reactive adults.

This work is all in mice. But Dr Bale has

now roped some men into the experiment,

too—namely 25 male students who have

provided regular semen samples in order

that the micro-RNAs therein can be tracked

and correlated with such stressful events

as sitting exams. The results of this are yet

to come in. But, with her mouse work

alone, it looks as if Ms Chan has cracked an

important part ofthe puzzle of intergenera-

tional epigenesis.

Response to stress is not, however, the

only thing in which micro-RNAs are impli-

cated. They are also suspected of involve-

ment in schizophrenia and bipolar disor-

der. To investigate this, a second speaker at

end of the second world war. Children

born of starved mothers were, as might be

expected, smaller than usual. Butthe chil-

dren of those children were also small. Ex-

periments carried out on mice confirm

these observations.

Stress city

In the case of mothers, it is now believed

that this process, called intergenerational

epigenesis, is caused by micro-RNAsfrom

the parent getting into eggs as they form in

a developing fetus. That makes sense. Eggs

are large cells, with room to accommodate

these extra molecules. But intergeneration-

al epigenetic effects can pass down the

male line as well. And how paternal micro-

RNAs come to be in an egg is a mystery, for

the sperm that would have to carry them

there are tiny and have no spare room.

Work by Jennifer Chan, a graduate student

at the University of Pennsylvania, has,

however, shed light on the process.

Ms Chan’s solution was described on

February 16th by her research supervisor,

Tracy Bale of the University of Maryland,

at the annual meeting of the American As-

sociation for the Advancement of Science,

in Austin, Texas. The crucial insight behind

her study was that micro-RNAs need not

actually get inside sperm cells as they form.

They could equally well be attached to

sperm just before sexual intercourse. Ms

Chan therefore concentrated her atten-

The American Association for the Advancement of Science

A generation game

AUSTIN

This year’s meeting of the AAAS heard about growing transplantorgans, safer

anaesthesia, quantum computers and tsunami detection. First, a new type of gene

Science and technology

Also in this section

68 Growing organs for transplants

69 Making anaesthesia safer

69 Reliable quantum computing

70 Tsunami detection