what makes us human?

Scientific American | Language Clues - Whole-genome comparisons in other species have also provided another crucial insight into why humans and chimps can be so different despite being much alike in their genomes. In recent years the genomes of thousands of species (mostly microbes) have been sequenced. It turns out that where DNA substitutions occur in the genome—rather than how many changes arise overall—can matter a great deal. In other words, you do not need to change very much of the genome to make a new species. The way to evolve a human from a chimp-human ancestor is not to speed the ticking of the molecular clock as a whole. Rather the secret is to have rapid change occur in sites where those changes make an important difference in an organism’s functioning.

HAR1 is certainly such a place. So, too, is the FOXP2 gene, which contains another of the fast-changing sequences I identified and is known to be involved in speech. Its role in speech was discovered by researchers at the University of Oxford in England, who reported in 2001 that people with mutations in the gene are unable to make certain subtle, high-speed facial movements needed for normal human speech, even though they possess the cognitive ability to process language. The typical human sequence displays several differences from the chimp’s: two base substitutions that altered its protein product and many other substitutions that may have led to shifts affecting how, when and where the protein is used in the human body.

A recent finding has shed some light on when the speech-enabling version of FOXP2 appeared in hominids: in 2007 scientists at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, sequenced FOXP2 extracted from a Neandertal fossil and found that these extinct humans had the modern human version of the gene, perhaps permitting them to enunciate as we do. Current estimates for when the Neandertal and modern human lineages split suggest that the new form of FOXP2 must have emerged at least half a million years ago. Most of what distinguishes human language from vocal communication in other species, however, comes not from physical means but cognitive ability, which is often correlated with brain size. Primates generally have a larger brain than would be expected from their body size. But human brain volume has more than tripled since the chimp-human ancestor—a growth spurt that genetics researchers have only begun to unravel.

One of the best-studied examples of a gene linked to brain size in humans and other animals is ASPM. Genetic studies of people with a condition known as microcephaly, in which the brain is reduced by up to 70 percent, uncovered the role of ASPM and three other genes—MCPH1, CDK5RAP2 and CENPJ—in controlling brain size. More recently, researchers at the University of Chicago and the University of Michigan at Ann Arbor have shown that ASPM experienced several bursts of change over the course of primate evolution, a pattern indicative of positive selection. At least one of these bursts occurred in the human lineage since it diverged from that of chimps and thus was potentially instrumental in the evolution of our large brains.

Other parts of the genome may have influenced the metamorphosis of the human brain less directly. The computer scan that identified HAR1 also found 201 other human accelerated regions, most of which do not encode proteins or even RNA. (A related study conducted at the Wellcome Trust Sanger Institute in Cambridge, England, detected many of the same HARs.) Instead they appear to be regulatory sequences that tell nearby genes when to turn on and off. Amazingly, more than half of the genes located near HARs are involved in brain development and function. And, as is true of FOXP2, the products of many of these genes go on to regulate other genes. Thus, even though HARs make up a minute portion of the genome, changes in these regions could have profoundly altered the human brain by influencing the activity of whole networks of genes.