Mice A re Here to Stay

Wherever people live, there are mice. It would be difficult to find another animal that has adapted to the habitats created by humans as well as the house mouse has. It thus seemed obvious to Diethard Tautz at the Max Planck Institute for Evolutionary Biology in Plön that the species would make an ideal model system for investigating how evolution works. BIOLOGY & MEDICINE_Evolution

Mice A re Here to Stay TEXT CORNELIA STOLZE

he mice at the Max Planck mice themselves only within a range of can be a key factor in the emergence of Institute in Plön live in their 30 to 50 centimeters, they convey high- new species. For Tautz, the house very own house: they have ly complex messages. mouse is a model for the processes of 16 rooms where they can Diethard Tautz and his colleagues evolution: it would be difficult to find form their family clans and have discovered that house mice be- another animal species that lends itself T territories as they see fit. The experi- have naturally only when they live in so well to the study of the genetic ments Tautz and his colleagues carry a familiar environment and interact mechanisms of evolution. out to study such facets as the rodents’ with other members of their species. “Not only is this species extremely communication, behavior and partner- When animals living in the wild are adaptable, as demonstrated by its dis- ships sometimes take months. During captured, they lose their familiar envi- persal all over the globe, but we also this time, the mice are largely left to ronment: everything smells and tastes know its genome better than that of al- their own devices. Humans enter their different, and they are no longer able most any other species,” says Tautz. Af- realm only to clean up and provide to move about freely. And most impor- ter all, scientists have been breeding them with food and water. tantly, they lack contact with the fam- and studying mice in the laboratory for The mouse house in Plön meets its ily – a key element in the lives of these more than a hundred years, observing inhabitant’s requirements fully. After extremely social animals. their behavior and decoding their ge- all, house mice also live in large family nome. Today’s laboratory mice are de- clans in the wild and maintain exten- A MODEL FOR EVOLUTION scendants of the house mouse, but they sive physical contact and communica- are far less genetically diverse than tion with each other. The squeaking fa- The mice in the mouse house, in con- their wild relatives. miliar to humans is only a small excerpt trast, can indulge in their entire reper- The house mouse’s first ancestors of the rodents’ vocal and sound reper- toire of behaviors. This is the only way lived around 500,000 years ago in the toire. Most of their communication oc- the latest evolutionary development of region that is now Iran, where they curs in the ultrasound range, which is the rodents can be studied, as the re- split into subspecies. When humans not perceptible to the human ear. And sults of research carried out in the past settled there around 14,000 years ago while the sounds can be heard by the showed that differences in behavior and started farming, a new age began

While the eyes of the house mouse (Mus musculus) tend to be underdeveloped, the rodent’s nose and ears play a very important role in the social life of its species: their vocalizations are so complex that the animals can even develop “dialects.” Such regional differences influence the mice’s choice of reproductive partner. Photo: MPI for Evolutionary Biology

1 | 18 MaxPlanckResearch 57 Mus musculus musculus

Mus musculus domesticus America Mus musculus molossinus

Original populations

Mus musculus domesticus Mus musculus castaneus

Mus spretus Mus spicilegus Mus macedonicus Mus musculus domesticus Colonization routes Contact zone between M. m. domesticus and M. m. musculus Additional contact zones

for the mice: they couldn’t resist the tures of just under 5 degrees Celsius. To functional genes can form from parts corn fields and storerooms of the first research this diversity, there are mice of the genome within a short period of farmers. It’s hard to imagine a more re- from all over the world living at the time. These genome sections had pre- liable and convenient source of food. Max Planck Institute in Plön: in addi- viously baffled researchers, as they From then on, the house mouse tion to mice from Germany and France, don’t contain any information that conquered the world in the wake of there are conspecifics from the Faroe Is- can be translated into functional pro- humans. As part of this process, it fol- lands, Spain, Austria, Kazakhstan, Iran teins. For this reason, up to 90 percent lowed different dispersal routes: the and even Taiwan. of the mouse genome was classified as eastern European house mouse (Mus junk DNA. However, the Max Planck musculus musculus) populated north- FROM VEGETARIAN working group discovered that these ern Asia and eastern Europe and adapt- TO CARNIVORE originally functionless DNA sequenc- ed to the continental climate there. es could give rise to new genes. “They The western European house mouse When necessary, the house mouse even really are complete reinventions – some- (Mus musculus domesticus) reached adapted its originally vegetarian eating thing that previously would have been western Europe, with its Atlantic cli- habits. The descendants of the former considered impossible,” explains the mate, on Phoenician merchant ships sea-faring mice, for instance, feed on evolutionary biologist. crossing the Mediterranean. Then, insects, worms and larvae. On the is- By genetically analyzing several with the first European seafarers, they land of Helgoland, they even became mouse species, Tautz and his colleagues made it as far as America, Australia, Tai- accustomed to eating dead sea birds. discovered that only a small percent- wan and even remote archipelagoes They are so flexible that, as long as they age of the DNA is translated into pro- such as the Faroe Islands. have a good food supply, mice don’t teins. Nevertheless, almost every DNA With the first European whalers, the even need direct access to water. section is transcribed into an RNA mol- mouse also penetrated almost as far as A few years ago, Diethard Tautz dis- ecule and can thus be a candidate for a Antarctica, populating regions where it covered a possible key to the evolution- new gene. Sections of DNA that are

quickly adapted to average tempera- ary success of the house mouse: new, read but not translated into proteins Graphic: TRENDS in Genetics, vol.19, no.1, January 2003

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Left page Origin and range of the house mouse: Two million years ago, their closest relatives M. spretus (yellow), M. spicilegus (gray) and M. macedonicus (green) separated; today their ranges overlap in different regions of Europe. Half a million years ago, subspecies of the house mouse then emerged in the area that is now India and Iran. The rodents gradually spread across the globe in the wake of the first farmers: the eastern European house mouse (M. m. musculus) migrated to northern Asia and eastern Europe, the southeastern Asian house mouse (M. m. castaneus) to eastern Asia, and the western European house mouse (M. m. domesticus) to western Europe. From there, the western European house mouse spread to all the other continents by ship. The different subspecies encountered each other in different regions of the world and cross-bred with each other (purple). One example of this is a narrow hybrid zone in central Europe (red line). A new hybrid subspecies, M. m. molossinus, emerged in Japan as a result of the contact between the eastern and Asian house mice. Right Diethard Tautz at the demonstration enclosure in the visitors room at the Max Planck Institute for Evolutionary Biology. The mice live here in a highly diverse environ- ment under nearly natural conditions. The actual experiment rooms are fitted with the same structural elements.

are thus called precursor genes or pro- togenes. Whether they become genes or not depends on the environment: if an RNA molecule assumes an import- ant function, the coding section of the DNA remains active and is retained. If the RNA molecule fails to find a useful task, the section becomes non-coding DNA again. But new genes also arise through a second mechanism: when a gene for a protein arises from an originally non-coding section due to a change in the DNA reading frame. A reading frame comprises three consecutive let- ters of the genetic alphabet. Each of these triplets stands for an amino acid into which the genetic code is trans- lated. If this reading frame shifts, new triplets arise and the sequence of let- ters can be translated into amino ac- ids. The scientists in Plön identified several genes that were overwritten due to such a change in the reading

Graphic: TRENDS in Genetics, vol.19, no.1, January 2003 Photo: Tom Pingel frame. One example is the Hoxa9 gene

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Diethard Tautz and his colleague – a gene that controls embryonic de- nosaurs became extinct, and in the most Christine Pfeifle have completed all the velopment. In rodents and primates, recent lineage leading to mice. preparations. The inhabitants will now this gene uses an additional, alterna- In addition, whenever the house be left undisturbed for months; their behavior is recorded by cameras. tive reading frame of this kind. mouse encountered a new habitat over The rooms are equipped with wood The researchers suspect that genes the course of evolution, new popula- shavings for burrowing and digging, frequently form anew. According to tions formed with different character- and with feeding dishes and water their findings, only around 60 percent istics and occupied different ecological bottles; the red “huts” with access tubes and removable lids serve as nests. of the mouse genes originate from the niches – a phenomenon known as The mice live in differently equipped early phase of evolution. Over time, adaptive radiation. “It was long be- environments depending on the nature apparently every section of the DNA lieved that this kind of adaptation to of the experiment: in this relatively is, at some point, read and tested to see new living conditions was a very slow unstructured experiment room, the whether it is suitable as a gene. “The process,” explains Tautz. “Recent stud- researchers are studying the social behavior and the territory formation non-coding sections of the genome are ies have shown, however, that animals of Mus spicilegus, a particularly social therefore a reservoir for new genes that sometimes adapt after just a few dozen species. Working together, the animals can thus help the animals rapidly generations – so, for mice, within just built themselves a nest in a corner adapt to new habitats. This harbors a few years.” under a pile of bedding (back) and assembled all the food supplies in the enormous potential for evolution, and middle of the room. we previously knew nothing about it,” ISLAND MICE GO THEIR says Tautz. OWN WAY The studies carried out at the Max Planck Institute in Plön also showed Tautz and his colleagues are able to that the emergence of new genes can in- study the consequences of adaptive ra- crease significantly under certain cir- diation and the very rapid adaptation cumstances. A lot of new genes arise af- of animals to new conditions using the ter major ecological changes: for house mouse in different locations in instance, a particularly high number of Germany, including the island of Hel- new genes emerged during the transi- goland. Located 50 kilometers from the

tion to the Cenozoic era, when the di- mainland, house mice arrived on this Photo: Tom Pingel

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Comparison of some ultrasounds of animals from the same subspecies, M. m. domesticus, from France (top) and Germany (bottom). The animals communicate using complex syllables that can differ from one region to the next. The females communicate a lot with each other – especially when they are alone together. The females make fewer and different sounds when in contact with males.

North Sea island on board ships only a graphical isolation, combined with limited extent, as the hybrid offspring few hundred years ago. “This is a mere new adaptations, is considered to be suffer from a weak immune system and blink of an eye in terms of evolution. one of the mechanisms for the emer- are more vulnerable to parasite infesta- Nevertheless, the animals on the island gence of new species. tions. This also has an impact on the already differ considerably from their This species formation, which is rodents’ intestinal flora. John Baines, a conspecifics living on the mainland,” known as allopatric speciation, is al- visiting professor at the Max Planck In- says the Max Planck researcher. ready further advanced in the eastern stitute in Plön, carried out a genetic Evolutionary biologists attribute and western subspecies M. m. musculus analysis of the biodiversity of these in- this to, among other things, differenc- and M. m. domesticus. The two still be- testinal bacteria. He found that the hy- es in the food supply: while house mice long to one species. However, they are brids’ intestinal flora includes fewer on the mainland have a mostly plant- clearly distinguishable both genetical- bacterial species, and that the different based diet, their relatives on Helgoland ly and in terms of their external appear- species also occur with different levels were forced to become accustomed to ance, and the two groups’ ability to re- of frequency. For example, a hybrid eating meat, as there is no farming on produce with each other is now limited. mouse has considerably more helico- the island. They now presumably eat This can be observed particularly well bacter bacteria than its purebred par- dead sea birds instead of plants, and in the range boundary of the two sub- ents. In humans, these microbes can their chewing apparatus has developed species along the climate divide be- cause intestinal ulcers. toward that of a predominantly meat-­ tween the Atlantic and continental cli- eating species. mates: their ranges overlap in a 40-ki- IMMUNE SYSTEM ALTERS The Helgoland mice hardly mix lometer-wide strip – known as a hybrid INTESTINAL FLORA with their relatives that are constantly zone – along this divide. The animals arriving from the mainland, so it’s only come into contact with each other here The scientists explain this as follows: a matter of time before the Helgoland and reproduce regularly. Different variants of genes for the im- animals become a separate species: Consequently, the genome of the mune system result in the formation of when two populations no longer ex- resulting hybrids consists of those of different immune cells. The hybrid change genes, different mutations arise the western and eastern subspecies. mice thus have different T cells. These in the two groups and they develop in However, the two species’ genomes are immune cells also occur in intestinal

Photo: Tom Pingel Photos: MPI for Evolutionary Biology different directions. This kind of geo- evidently now compatible only to a tissue and evidently have an adverse ef-

1 | 18 MaxPlanckResearch 61 62 produce offspringtogethercan leadto males and females can theoretically highly diversegroupin which all ing pointforseparation.In this way, a ences inbehaviorareoften thestart- solely byphysicaldifferences; differ concludes DiethardTautz. populations inevitablydriftapart,” brid are less fitthan their parents,the the longterm.“Ifoffspringofahy subspecies can’t innature survive arate species.Crossbreedsofthetwo eventually giverisetocompletelysep- each otheruntilthetwosubspecies forms ofmouseconstantlyreinforce this way, thedifferencesbetween brids overthecourseofevolution.In prevent reproductionbetweenthehy- tween differentgeneregionsthatcan complex networkofinteractionsbe- mer colleagues of Tautz, discovered a Leslie Turner andBettinaHarr, twofor ing themtoproducefeweroffspring. severely impairedinthehybrids,caus infections thantheirparents. brids aremorepronetointestinaltissue appear tobenefitthemice,ashy- fect onthebacteriathere.Thisdoesn’t MaxPlanckResearch 1 MaxPlanckResearch But aspeciessplitisn’t triggered In addition,spermmaturationis | 18 - - - - moniously –beitbecausetheanimals populations thatceasetooperatehar- Massif Centralinourmouse house, the samespeciesfrom French brid zone,togetherwithmembers of around Cologne,farwest of thehy France differintheirmating behavior. western Germanyandthesouthof example, thatwesternhousemicefrom tions. The researchers discovered, for ties” form between individual popula- and ensuresthatdifferent“personali it isknown, controls several behaviors partner selection. ThisPWSregion, as that cruciallyinfluencestheanimals’ that ismadeupofseveralgenesand tered acomplexinthemousegenome Tautz andhisteamrecently encoun- GENES FORPARTNER SELECTION this sympatricspeciation. within apopulation.Researchers call cipient isolationofoneormoregroups havior arethemainreasonforin- at adifferenttime.Suchchangesinbe nests, orbecausethefemalesarefertile because one group builds different no longerfindeachotherattractive, “If weputanimalsfromthe area - - - separated fromeachotherlong enough populations clearlywere physically tinues. TheGermanandFrench mouse cause ofthepaternalpreference con- populations, butthesearch forthe contributes totheseparation ofthe belonging tothesamesubspecies.This as itwere,differentlanguages–despite the soundstheymake,andthusspeak, together,” saysTautz. other, particularlywhentheyarealone males communicatefarmorewitheach that fe birds. But then we observed make, justlikethechirpingofsong- mating signals through the sounds they that themales,inparticular, convey 70 kilohertz.“We originallysuspected sounds intheultrasoundrangeof50to is conveyedthroughodorantsand that, in mice,a partner’s attractiveness es suchpreferences. What isknown igin astheirfather.” preference forpartnersofthesameor- and oneFrenchparentlatershowa spring: themicewithoneGerman surprising happens with their off- ly,” saysTautz. “However, something they allmatewitheachotherinitial- It is still unclear precisely what caus- French andGermanmicedifferin -

Photo: Tom Pingel BIOLOGY & MEDICINE_Evolution

Left page Diethard Tautz (standing), Johana Fajardo, Derek Caetano-Anolles, Chen Xie, Kristian Ullrich and Wenyu Zhang (clockwise) discuss their projects. Right DNA sections with varying degrees of activity in the genomes of different mouse species (black lines indicate the relationships between them): dark gray boxes represent regions that are translat- ed into RNA molecules and the height of the triangles above the boxes indicates the volume of RNA produced. While 10 percent of the DNA in all the animals is used identically (box on the left), non-coding sections are read at varying levels of intensity. The resulting RNA molecules are retained only if they offer an evolutionary advantage. New genes can then form from these sections.

for the initial indications of separate development to emerge within the TO THE POINT subspecies. l In addition, another aspect of sexu- The modification of existing genes isn’t the only thing that gives rise to new char- acteristics in evolution: completely new genes can also be created from previously al behavior accelerates speciation: al- non-coding sections of DNA. This happens especially when major ecological chang- though mice have many different sex- es occur or when species populate new habitats.

ual partners, the researchers also regu- l As hemerophiles – animal and plant species that thrive in habitats altered by hu- larly observed cases of fidelity and mans – house mouse populations and subspecies have spread throughout the world inbreeding. Large families in which fa- and repeatedly adapted to new environmental conditions. Accordingly, they consti- thers produce offspring with daughters tute a natural experiment on the part of evolution – one that enables scientists to study the emergence of new species. and mothers with sons often arise in l the behavioral rooms. This promotes Differences in behavior, for example in partner selection, and in the formation of social systems are the first steps in one species splitting into two separate species. the formation of genetically uniform groups and thus strengthens the specia- tion process. This natural inbreeding is GLOSSARY also the reason why mice are such a good genetic and biomedical model Allopatric speciation: Individuals of one species are separated by external factors such system: the requisite genetically uni- as mountains or estuaries. Over the long term, this spatial isolation results in the accu- mulation of different mutations in the subpopulations and, consequently, the formation form inbred strains are particularly easy of genetic differences. The animals can no longer reproduce successfully with each oth- to establish with mice. er, and two new species form. When species split in the absence of spatial separation, it The research by Diethard Tautz and is referred to as sympatric speciation. his colleagues shows that mice are Radiation: Diversification of a group of organisms or a species into a larger number of much more than pests and carriers of new species, which adapt to new ecological niches and thus form new characteristics. disease. On the contrary, their prolifer- This can cause an abrupt increase in the number of new species, for example when a new habitat is populated. In contrast, the fragmentation of an originally contiguous ation across the globe is an object les- habitat can also trigger the emergence of new species, but this is a continuous process son in how organisms can adapt to new that unfolds over a long period of time. New species can also take over the vacated eco- habitats. The different house mouse logical niches when competitors disappear, as was the case with mammals when the di- populations on earth constitute evolu- nosaurs went extinct, for example. A successful evolutionary innovation can also result tionary experiments from which new in the emergence of many new species.

Photo: Tom Pingel Graphic: MPI for Evolutionary Biology species could one day emerge.

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