The public consortium that assembled the human genome dream team considered Evan Eichler a "must have." And for good reason: Eichler, an expert in analyzing genomic duplications, was able to combine computational and experimental techniques to identify the regions and determine the approximate percentage of the human genome in large, recently duplicated segments—a task that required overcoming significant problems with the sequence data available at the time.
An estimated five percent of the human genome contains duplicated sequences of genes. Eichler and others recently showed that the human genome changes constantly—and duplicate sequences are among the fastest evolving regions, telling an interesting evolutionary tale and contributing to human disease.
Eichler focuses on the role of duplicate regions within the human genome. How did this complex architecture evolve? How variable are these regions? How do they contribute to disease? Have genomic duplications helped humans, or primates, adapt?
Using computer software to screen randomly shuffled sequences, Eichler and colleagues located all the human genome's large duplicated sequences and built a map of evolutionary "hot spots"—sites likely to undergo repeated chromosomal rearrangement and thus evolve quickly. Because duplicated regions are particularly susceptible to breaks and rearrangement as genes naturally recombine, they underlie many genetic diseases. Eichler's lab plans to search for specific regions that can be linked to inherited conditions, such as congenital birth defects and mental disability.
To gain a broader evolutionary perspective, Eichler and colleagues have compared the distribution of genomic duplicates between the human and chimpanzee genomes. They have demonstrated that a significant fraction of these genes expressed differently in the two species' brains occur in duplicated sequences. Eichler's lab intends to build on this work with studies of natural genome variation between humans and other primates. One long-term goal is to reconstruct the evolution of every duplicated sequence in the human genome that has arisen in the last 40 million years—what evolutionary biologists consider recent history.
Eichler is particularly focused on genetic diseases caused by chromosomal abnormalities, such as Prader-Willi and Angelman syndromes. At the genomic level, these diseases are characterized by chromosome instability that overlaps areas of evolutionarily recent genome duplication. Those who have followed Eichler's work closely say these diseases are a potentially rich source of information, and he's just the person to lead the charge in this area of unexplored human variation.