Dr Mukund Thattai, a faculty member at the National Centre for Biological Sciences (NCBS) Bangalore, wants you to play a card game and discuss your winning strategies with him. Your strategy may uncover the reasons why prokaryotes and eukaryotes reproduce the way they do. "Each strategy is a hypothesis which I can test. In this sense, this game is about outsourcing the hard parts of making a hypothesis to a bunch of clever card players. It is a unique way of doing science, not just a pedagogical tool," says Dr Thattai.

Nearly two billion years ago, cells we now call eukaryotes evolved with traits such as a nucleus, organelles, and sexual mode of reproduction. They had to compete with prokaryotes like bacteria that made up all life then. Though prokaryotes are still the dominant form of life on earth, eukaryotes managed to carve out a niche and survive. The gameplay in Gene Rummy (a pun on gin rummy) simulates reproductive patterns and strategies in prokaryotes and eukaryotes. It is a competition between sexual reproduction of eukaryotes and fission-like asexual reproduction in prokaryotes.

It is a misconception that only eukaryotes mate. When viewed as an event of genetic exchange, the mating process in prokaryotes takes place more often than eukaryotes. Genetic exchange is important for sustenance of a species for two reasons. One, most mutations are deleterious, and a reverse mutation is highly unlikely. If cells exchange genetic material, some offspring will have neither of the mutations its parents have; hence it is fitter. Two, mutations in different cells that are nascent by themselves, can have their full impact when brought together through genetic exchange, thus driving evolution forward. So DNA flows across cells regardless of their mode of reproduction.

Prokaryotes have practically the whole world to exchange DNA with -- and they do so more often - whereas eukaryotes exchange DNA only within their species by advertising their identity, for which they evolved elaborate mechanisms, Anjali Jaiman, a student in Thattai's group, studies the role of the Golgi apparatus in constructing cell-surface molecules called glycans.These glycans are examples of species-advertising molecules: a mouse's sperm is not attracted to a rat's egg because their glycans are not compatible.

Maintaining the complex Golgi machinery imposes an explicit cost on eukaryotes. There is also an implicit cost: eukaryotes have a limited number of partners to exchange genetic material with. But there is a huge benefit to the eukaryotic strategy: genes from a partner closely related to you are likely to be more useful than a random gene from the environment. Prokaryotes exchange genes more often but each gene is likely to be less useful; eukaryotes exchange genes less often with fewer partners but each gene is likely to be more useful.

How then do eukaryotes manage the costs and succeed as a species? What strategies do they employ? Initially, Dr Thattai modelled this system on a computer by putting in parameters like genetic variability, recombination and organisms trying to maximise their fitness. The general ideas were correct, but he was unable to explore the model by putting in different hypotheses. Every time he changed a condition, he had to rework the model from scratch. It was going to take too long. Also, the computer program was not going to give a general 'strategy' to win the game.

That is when he turned to a game played by humans. "The idea was to use humans as computers... the players will come up with something that I did not previously notice," says Dr Thattai. One can run a simulation of the game and get statistical data of the results. But one cannot know the points of frustration, the points that tipped the balance in favour of 'eukaryote' players.  "A human player will know all of that. Even if the game is the exactly the same as the simulation, the human player will have a completely different view of the game," says Dr Thattai. Incidentally, it took a long time to perfect the game-mechanics -- to put in just enough rules to make the game enjoyable.

In Gene Rummy, a player decides to play as an eukaryote or a prokaryote (they "go-pro") after the cards are dealt. The eukaryote player places a card -- presumably from the most frequent suit in his/her hand -- face up (and picks a fresh card from the deck). That suit becomes his/her 'species'. To win the game, eukaryotes should produce a sequence in the suit of their species while prokaryotes can do it in any suit. As in Rummy, in each round, each player gives up one card and picks a fresh card as follows: prokaryotes exchange with the deck in the middle and eukaryotes exchange only from fellow eukaryotes of the same species. Though it seems eukaryotes are limited by their species population, it turns out eukaryotes have greater odds of winning.

Many rules had to be added to make gameplay interesting, which can be seen in the detailed rule sheet. But the basic idea is simple -- it is beneficial to me to exchange genes within my species, but there is a cost to somehow detect cells of my species.

The real analogy between the model and the game is not very obvious. "When I first made the game, the analogy was clearer. I had to make the game interesting to human players, so I added a lot of ingredients for game play. Now I need to sit back and rethink what the analogies are before I ask research questions. That is also worth talking about to players," says Dr Thattai.

About Gene Rummy:

A detailed rule-sheet can be downloaded from here . Dr Mukund Thattai will be very happy to listen to your experiences, memorable or otherwise, and the winning strategies you came up with. So, grab a deck of cards and get cracking!

E-mail address: thattai@ncbs.res.in