The Scientist: Alon Keinan

“The next major explosion is going to be when genetics and computers come together,” American writer and futurist, Alvin Toffler, once said. A manifestation of this explosion apparently resides with one of Cornell’s newcomers, Professor Alon Keinan, biological statistics and computational biology.

Alon Keinan was born and raised in Israel. He immigrated to the United States for postdoctoral research. “It’s pretty mandatory to have post-doctoral experience from a good university outside of Israel in order to then get a faculty position in Israel,” he said.

While Keinan had originally planned to someday return to Israel, working at universities such as Cornell, Harvard and the Massachusetts Institute of Technology (MIT) has changed his mind: “After being in the US for a while, I stopped wanting to go back to Israel for all kinds of different reasons … The level of the universities here … the colleagues, the kind of funding you can get here to do your research and so on is at least one level above what you would get in Israel.”

With a PhD from Tel Aviv University in computer science, Keinan curiously shifted his focus to genetics upon moving to the United States. “What really interested me all along, in parallel to my studies, is evolution in general … As part of my PhD, I was involved in genetic algorithms and evolutionary computation in general … as I was heading towards the end of my PhD I realized that what I would like to do next is cross the line and go closer to the other side of real evolution, real biology.”

As for his current work, Keinan says that the field that best describes his research is “human population genomics,” or the study of human chromosomes, including DNA sequencing and other genetic mapping efforts. According to Keinan, his research spans three separate but related fields.

“On the first level I’m using genetic variation within human populations and between different human populations to study about human evolutionary history,” he said. His most recent results in this field were published in Nature Genetics magazine earlier this year. Stemming from the widely accepted “out of Africa” hypothesis, Keinan’s research rests on the theory that every living human being descended from a small group in ancient Africa who then migrated throughout the world.

Keinan’s most recent study compares autosomes — the non-sex chromosomes — with chromosome X, the sex chromosome that females inherit from each parent and males inherit from their mother.

Using various mathematical and statistical comparisons, Keinan and his mentor, David Reich, arrived at the conclusion that the original “out of Africa” population consisted of more males than females, followed by other groups of mostly male migrants. “Males carry only one copy of chromosome X, while females carry two, [which] would explain all the asymmetries that we see between [chromosome] X and the autosomes,” Keinan explained.

In a population consisting of an equal number of males and females, it is expected that there are three copies of chromosome X for every four autosomes. However, after calculating the ratio within a West African population (which was used as a substitute for the original Africans) only around two copies of chromosome X were found, thus displaying an increased ratio of X- related drift. This indicated that males play more of a part in this out of Africa dispersal.

On the second level of his research, Keinan says that once there is a basic understanding of how history in general has shaped human genetic variation, it is possible to look for specific genes that seem different from what is expected by genetic drift, or a type of evolution that, along with natural selection, changes the characteristics of certain species over time.

”We focused very carefully on four brain related genes, [which were chosen because] there is evidence that there has been some selection going on since the separation between human and chimpanzee … What interested us [was] to look more recently within human populations and see whether these genes have been under very recent selection … in the last 100,000 years.” The results were mixed: two genes show a strong signal of being under recent selection, while the others have not been as differentiated.

On the third and final level of his research, Keinan says he is trying to understand how genetic drift has shaped our genome and bring this understanding to medical genetic studies. As part of the research in this field, Keinan is currently taking part in an international experiment, the Thousand Genomes Project. “[For the project], we are sequencing 2000 people from all across the world…with one of the goals being to find genetic variances that are pretty rare…[because by] using these rare findings we have more of a chance to figure out what’s going on with common diseases.”

With a recently successful study about male migration from Africa as well as his participation in the Thousand Genomes Project, Alon Keinan is a very busy man. He is excited to be continuing his research here at Cornell, and will, in about three weeks, be visiting Hawaii to attend The Annual Conference of the American Society of Human Genetics.