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Why Are Some Mice (and People) Monogamous? A Study Points to Genes
New York Times, April 19, 2017

The oldfield mouse doesn’t seem extraordinary. With soulful black eyes and tiny teacup ears, the rodent lives a humdrum life scurrying about meadows and beaches in the Southeast.

But field biologists have long known that when it comes to sex and family life, this mouse is remarkable: Peromyscus polionotus is monogamous — an exception among mammals — and a solicitous parent.

Fathers and mothers will dig burrows together and build elaborate nests when pups are on the way; after they’re born, the father will help tend to the pups, retrieving them when they fall out of the nest, licking them, and huddling to keep them warm.

In a pioneering study published on Wednesday in the journal Nature, researchers at Harvard University identified a genetic basis for this distinctive behavior. It is the first time that scientists have linked DNA to variations in parenting habits among mammals.

Dieter Lukas, an evolutionary biologist at the University of Cambridge who was not involved in the research, hailed the study as a sophisticated tour de force, saying that uncovering these links “is like designing a tool to follow individual threads through a large colorful tapestry.”

The findings may one day help scientists make sense of how human couples bond and care for their children. Mammals share many of the genes governing the production of hormones and neurotransmitters in the brain.

Variations in how they function may explain why most species are promiscuous, why a few are monogamous — and why some, like humans, are somewhere in between.

“We can go from the bottom up and build our knowledge base, and then ask questions about human biology,” said Gene E. Robinson, a biologist at the University of Illinois who was not involved in the new work.

In the vast majority of mammal species, males mate with as many females as possible and offer no help with raising offspring. Oldfield mice belong to the about 5 percent of species in which a male forms a long-term bond with a single female and offers paternal care.

Hopi E. Hoekstra, an evolutionary biologist at Harvard University and senior author of the new study, first became aware of oldfield mice as she was digging through dusty old reports from naturalists.

Their closest living relatives, deer mice, dwell in forests instead of open spaces, she learned, and they live promiscuously instead of monogamously. In the wild, deer mice and oldfield mice never interbreed.

But the two species will do so in laboratory experiments if a single male and female are placed in a cage together. Their offspring are healthy and fertile.

Dr. Hoekstra realized that it might be possible to compare parenting behaviors in the two species, and then see how their hybrid offspring behaved. The differences could lead the scientists to the genes influencing these behaviors in each species.

Andrés Bendesky, a postdoctoral researcher at Harvard, began the research by observing as each mouse species raised its young in the lab. He tracked a number of parenting behaviors, from building a nest for pups to licking them.

Deer mice put in less parenting, but it was possible that the cause was not genetic. Perhaps they were neglected by their own mouse parents, and the behavior was learned. To compare nature and nurture, Dr. Bendesky and his colleagues moved deer mice pups into oldfield nests — and vice versa.

The swap, they found, had no effect on how the mice behaved when they grew up: Oldfield parents were still solicitous, deer mice much less so.

Dr. Bendesky and Dr. Hoekstra concluded that the differences in the mice’s behavior must be anchored in their DNA. So the researchers carried out a large-scale breeding experiment.

They paired five mice from each species, producing 30 hybrids, which then yielded 769 pups of their own. The scientists observed as these second-generation hybrids raised a third generation of pups, measuring the same parental behaviors as before.

As parents, the second-generation hybrids ran the gamut. Some hardly tried at all, like purebred deer mice, while others put in a moderate effort. But other hybrids provided as much care as oldfield mice. A few proved to be super-parents, building remarkably elaborate nests.

This spectrum offered Dr. Hoekstra precisely the opportunity she had hoped for. Her team scanned the DNA of the hybrids and found twelve stretches of DNA — known as loci — clearly linked to parenting behavior.

Some influence just a single behavior. One locus, for example, determined how well the mice built nests. Hybrid mice that inherited two copies of the oldfield locus built more elaborate nests than those inheriting this DNA only from the deer mice.

Intriguingly, however, other loci seem to affect several behaviors at once.

One DNA stretch was linked to four traits: how much mice lick their pups, how long they huddle, how long they handle their young, and how likely they are to retrieve a pup if scientists plucked it out of the nest.

It makes sense that some genetic mutations might have only very narrow effects, while others have a broad reach — perhaps because they alter an animal’s mood.

Many of the loci, too, were important in one sex but not the other. One seemed linked to the amount of time mouse fathers handled pups and huddled with them, for example. But it had no such effect in the mothers.

Dr. Hoekstra and her colleagues speculate that this is evidence that males and females may have taken different evolutionary paths toward monogamy. Different genes mutated, causing their brains to change in different ways.

One drawback to this type of breeding experiment is that it points scientists only to stretches of DNA, each of which may contain hundreds of genes. Researchers have to inspect each to find the one gene that matters.

In the new study, the researchers focused on the locus associated with nest building. They carefully examined the 498 genes it contained, homing in on one encoding of a hormone called vasopressin.

In the bloodstream, vasopressin controls blood pressure and the flow of water into the kidneys. But some of the hormone is produced in the hypothalamus of the brain, and researchers have found that here it influences behavior.

In some situations, the hormone makes rodents anxious and depressed. But when rats have young, a surge of vasopressin helps push them to start caring for their pups.

Deer mice make three times more vasopressin in the hypothalamus than oldfield mice, Dr. Bendesky and his colleagues found. To see how that mattered, they injected vasopressin into the brains of oldfield mice, wondering if they’d behave more like the other species.

They did. Suddenly the mice made simple nests more similar to those of deer mice. Yet the injection didn’t alter their parental care in any other way.

Humans have a staggering range of relationships, compared with other mammals. In some cultures, men and women live monogamously, while in others one man may be married to several women. In a few societies, one woman marries a number of men.

But we may share some biologic similarities with species like oldfield mice, making research like Dr. Hoekstra’s a source of potential clues.

Our brains also make vasopressin, for example, and some studies have found intriguing hints that it influences parents. In a small study published in 2012, researchers found that fathers experienced a surge of vasopressin in the brain at the sight of their own infants.

But Dr. Bendesky cautioned that the vasopressin gene would probably turn out to be just one of many that influence oldfield mice. Though it is strongly linked to parental behavior, the vasopressin gene accounts for 6.7 percent of the variation in nest building among males, and only 2.9 percent among females.

The genetic landscape of human parenting will turn out to be even more rugged, Dr. Bendesky predicted.

“You cannot do a 23andMe test and find out if your partner is going to be a good father,” he said.

Copyright 2017 The New York Times Company. Reproduced with permission.
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