It's one of the basic questions of our existence: what makes humans different from our close cousins, the apes? Are we distinct owing to many genetic mutations or, as some have postulated, just a few key base changes? A new study by Enard et al. in Nature suggests that two amino-acid mutations in one gene might have contributed greatly to the evolution of modern humans.

One defining trait for humanity is our ability to communicate through language, and thus develop culture over time. In a 2001 Nature paper, Lai et al. reported that mutations in the FOXP2 gene impaired some humans' ability to speak and to use language properly. The FOXP2 protein is a forkhead transcription factor that presumably controls the expression of other genes. So, it might seem like a perfect lead to the biological basis of that unique trait — the use of language.

This discovery led Enard et al. to scrutinize FOXP2 sequence for polymorphisms in humans and between humans and other species. Although no amino-acid polymorphisms were found in various human populations, all humans have two amino-acid changes that are specific to our lineage, and that are not shared with either four ape species or our distant mouse relatives. Furthermore, one of these changes might be functionally important, as it creates a target site for phosphorylation on, and therefore regulation of, the FOXP2 transcription factor protein.

When Enard et al. studied nucleotide polymorphisms in FOXP2 they found that the pattern of polymorphisms suggests that it is the genomic region that has experienced strong positive selection. Amazingly, selection has been maintained even though Newbury et al. reported that this chromosomal region undergoes recombination at five times the genomic average. As the nearest gene is 286 kb away, the most likely explanation is that FOXP2 itself is the target of the positive selection.

Finally, Enard et al. used evolutionary modelling to speculate that the human-specific changes occurred at the time of emergence of anatomically modern humans. So, they propose that the development of language, a key factor in allowing early humans to migrate and spread to new territories, was aided by key changes in FOXP2, which quickly swept through the human population. Although other genes are certainly involved in the process, Enard et al. have set forth a blueprint for how to determine the roots of our human family tree, one gene at a time.