Innovation in genetic variation research garners Jonathan Pritchard HHMI investigator appointment at University

Jonathan Pritchard, Professor in Human Genetics and the College, has been selected to become a Howard Hughes Medical Institute investigator.

The institute is committing more than $600 million to support 56 of the nation’s top scientists over their first term of appointment. HHMI chose the 56 scientists from among 1,070 applications submitted in a nationwide competition.

“These 56 scientists will bring new and innovative ways of thinking about biology to the HHMI community,” said Thomas Cech, president of HHMI. “They are poised to advance scientific knowledge dramatically in the coming years, and we are committed to providing them with the freedom and flexibility to do so.”

The investigator program employs more than 300 of the nation’s most innovative scientists, who lead Hughes laboratories at 64 institutions. These scientists are widely recognized for their creativity and productivity: 124 are members of the National Academy of Sciences and 12 have been honored with a Nobel Prize.

The principle of “people, not projects” guides HHMI, which appoints scientists as Hughes investigators rather than awarding research grants. HHMI investigators have the freedom to explore and, if necessary, change direction in their research. Moreover, they have support to follow their ideas to fruition, even if that process takes many years.

Pritchard has studied “a wider range of topics than most biologists cover in a lifetime,” according to the HHMI. He has analyzed the patterns in human DNA created by historical migrations, the consequences of natural selection and even the tantalizing question of whether modern humans and Neanderthals interbred.

 “Sometimes I have a hard time describing exactly what I work on,” admits the Chicago biologist. “But almost everything I do is connected to understanding aspects of human genetic variation.”

 Pritchard grew up in England, about an hour away from Charles Darwin’s countryside manor. He shares Darwin’s fascination with natural history. “I collected insects and snakes when I was younger, and still do quite a bit of birding,” he said. But he also was captivated by mathematics. “Applying mathematics to understand the evolutionary and genetic mechanisms that create biological diversity was a natural way for me to combine my interests,” he said.

Since coming to the University in 2001, he has been working to understand the links between genetic variation and human traits. When a particular genetic variant gives an individual a survival advantage in a given environment, such as being able to survive malaria or digest milk from animals, that individual has a greater opportunity to pass on his or her genes to future generations. As a result, the variant can become more common in a population. This natural selection of advantageous genes—the raw material of evolution—leaves signals in the DNA that can be detected when researchers compare human genomes.

In a 2006 paper, Pritchard and his colleagues described the identification of several hundred DNA regions in various human populations that show signals of selection. Included within those regions are genes that influence reproduction, olfaction and degradation of environmental toxins, skin pigmentation and skeletal development.

Using more extensive data that have recently become available, his group has been examining the relative roles of chance (which can lead to changes in the gene pool known as genetic drift) and selection in favoring these genes. “Selection may be a weaker force than we thought,” he said. “It seems to be a combination of drift and selection acting together.”

But gene expression is the area he finds especially promising. He plans a comprehensive analysis, cataloging all of the variations in DNA that are common among the human population and have an impact on gene expression. His goal is to determine how these variations alter gene regulation throughout the genome and to link them to diseases and other traits.

“Selection and gene regulation are where we think we can have the biggest impact in the next few years,” he said.