Whether we become what we are through our genes or through our experiences in life is the old chestnut that this debut novelist tackles with refreshing originality, wit and verve.

The memorable comic hero, Professor Don Tillman, a university teacher of genetics living in Melbourne, exhibits characteristics of Asperger's syndrome  although does not yet realise it  and his compulsively readable first-person narration demonstrates the gulf between his literal interpretations of human behaviour and the actuality, creating considerable dramatic tension. "Predicting the impact of actions on other people is incredibly difficult," he explains, deadpan.

The subject of autism has been tackled in fiction before, most famously in The Curious Incident of the Dog in the Night-Time by Mark Haddon, published in 2003 and currently on stage in the West End. Whereas that novel filtered life through the perspective of 15-year-old Christopher Boone, Simsion here explores the effects of the condition upon adulthood  and his comic approach is what makes this novel distinctive. "I am an expert at being laughed at," Don acknowledges, but this is far more subtle than two-dimensional comedy, for while we laugh at him, we also come to laugh  and cry  with him, as Simsion skilfully creates empathy for Don and his struggle to empathise.

Intent on marrying, the chronically single professor embarks upon "The Wife Project", devising an obsessively detailed screening questionnaire for prospective partners, ruling out smokers, drinkers and bad time-keepers, among many others. The feisty young smoker Rosie is far from his ideal but he becomes engrossed in "The Father Project", helping her to search for her biological father, a detective puzzle that involves ingenious ways of garnering DNA samples from suspected fathers  which cleverly reveals much about Don's own identity.

What role should emotion play in life? Don's initial instinct is "to be vigilant that emotions do not cripple us". The novel excels in showing how human character is far from fixed, demonstrating Don's development as he gradually grows in emotional literacy and self-awareness through reading, observation and "educational material", devouring films from When Harry Met Sally to To Kill a Mockingbird, until he "slowly began to make sense of it all".

This entertaining romantic comedy began life as a screenplay, which is reflected in the pacy plot that takes the protagonists on a journey from Melbourne to New York, and through the fascinating terrain of human DNA, shedding insight into the science of how we are what we are. First published in Australia, the book has become a global phenomenon, with publication deals in more than 30 countries, reportedly earning the author advances of more than £1.2m.

Filled with engaging specificities of character and setting, the professor's struggle to understand the "fundamental, insurmountable problem of who I was" also becomes a poignant universal story about discovering how best to reconcile logic and emotion, head and heart, and connect our lives with others.

The hero of The Rosie Project is one of those rare fictional characters destined to take up residence in the popular consciousness. Don Tillman, Graeme Simsion's geeky, gawky geneticist, seems set to join Adrian Mole and Bridget Jones as a creation with a life beyond the final chapter. The Rosie Project may be a lighthearted romp to be gobbled up in a couple of sittings, but it is also an important book, because Don is on the autistic spectrum.

Autistic characters have featured in many works of fiction. The most notable is Christopher Boone, the innocent savant of Mark Haddon's The Curious Incident of the Dog in the Night-Time, whose immutability is the touchstone for the moral behaviour of all the other characters. But in Don we find, for I believe the first time, a thoroughly comic autistic hero. Some readers may feel, uneasily, that Don is a figure of fun, but for me Simsion pitches the humour perfectly. Yes, we laugh at Don, but we're rooting for him.

Don is 39, fit, solvent, intelligent. "Logically, I should be attractive to a wide range of women," he states, but on a series of disastrous dates, logic fails to do its stuff. Finding a wife is like looking for a bone-marrow donor, Don decides. He devises a questionnaire ("Question 35: Do you eat kidneys? Correct answer is c) occasionally") to track down the perfect partner. "I believe I can eliminate most women in less than forty seconds."

Enter Rosie, who ticks none of the right boxes. Clearly, to the reader familiar with the romcom format, she's the one, but as Don himself observes: "Humans often fail to see what is close to them and obvious to others." Misunderstandings and slapstick setpieces abound, as when the virginal Don works his way through a manual of sexual positions with the aid of the laboratory skeleton, to the consternation of the dean. How will this unlikely leading man, who shops, eats and socialises according to a rigid set of self-imposed rules, work his way towards happiness with emotional, volatile, utterly unautistic Rosie?

Rosie wants to trace her biological father. Don has the know-how and the lab equipment; together they collect DNA samples from a range of suspects. This isn't easy. "The best I had been able to think of was to construct a ring with a spike that would draw blood when we shook hands, but Rosie considered this socially infeasible." I didn't take to moody, self-absorbed Rosie, but I'm not sure we're meant to. Simsion subtly shows how the script Rosie's written for her own life blinkers her just as effectively as does Don's inability to read social cues.

Don doesn't regard himself as autistic: he lectures on Asperger's syndrome but fails to link its salient features with his own. "Asperger's isn't a fault. It's a variant. It's potentially a major advantage," he tells his audience; at the heart of The Rosie Project lies the belief that we all behave according to our own "variant", and what passes for normal can cause as many problems as any named condition. Don's friend and colleague, the aptly named Gene, is on a mission to have sex with women of as many nationalities as possible; he marks each conquest with a pin on a world map. "North Korea predictably remained without a pin," records deadpan Don. Don likes Gene's wronged wife Claudia as much as he likes any other human, but at first he accepts his friend's behaviour as part of his professional remit  "Sexual attraction is Gene's area of expertise". As Don's involvement with Rosie deepens, and he allows "feelings" to disrupt his "sense of wellbeing", he becomes aware that Gene's "variant", accepted as normal, is in fact corrosive, dysfunctional and  yes  wrong.

With such awareness comes pain. As Don breaks down his boundaries and becomes a player in the game of life, he finds that he can be unprofessional, deceitful  a rule-breaker. "I had been corrupted. I was like everyone else," he mourns. Though the comedy never falters, this moral seriousness saves the book from being simple-minded.

Simsion is brilliant at getting us to read between Don's literal-minded lines. "I'm not good at understanding what other people want," Don tells Rosie. "Tell me something I don't know," she sighs. "I thought quickly ...Ahhh ... the testicles of drone bees and wasp spiders explode during sex." This good-hearted, pacy, thoroughly enjoyable novel takes a significant step towards showing that all human variants are a potential source of lifeaffirming comedy.