The Little Rock Zoo

.The Little Rock Zoo needs to step up and care for the animals better! Please read the several artciles here with deaths, sickness and a bald chimp!

Wednesday, April 22, 2009

What Makes Us Human

  • "Chimpanzees are the closest living relatives of humans and share nearly 99 percent of our DNA.
  • Efforts to identify those regions of the human genome that have changed the most since chimps and humans diverged from a common ancestor have helped pinpoint the DNA sequences that make us human.
  • The findings have also provided vital insights into how chimps and humans can differ so profoundly, despite having nearly identical DNA blueprints.

Six years ago I jumped at an opportunity to join the international team that was identifying the sequence of DNA bases, or “letters,” in the genome of the common chimpanzee (Pan troglodytes). As a biostatistician with a long-standing interest in human origins, I was eager to line up the human DNA sequence next to that of our closest living relative and take stock. A humbling truth emerged: our DNA blueprints are nearly 99 percent identical to theirs. That is, of the three billion letters that make up the human genome, only 15 million of them—less than 1 percent—have changed in the six million years or so since the human and chimp lineages diverged.

Evolutionary theory holds that the vast majority of these changes had little or no effect on our biology. But somewhere among those roughly 15 million bases lay the differences that made us human. I was determined to find them. Since then, I and others have made tantalizing progress in identifying a number of DNA sequences that set us apart from chimps.

An Early Surprise
Despite accounting for just a small percentage of the human genome, millions of bases are still a vast territory to search. To facilitate the hunt, I wrote a computer program that would scan the human genome for the pieces of DNA that have changed the most since humans and chimps split from a common ancestor. Because most random genetic mutations neither benefit nor harm an organism, they accumulate at a steady rate that reflects the amount of time that has passed since two living species had a common forebear (this rate of change is often spoken of as the “ticking of the molecular clock”). Acceleration in that rate of change in some part of the genome, in contrast, is a hallmark of positive selection, in which mutations that help an organism survive and reproduce are more likely to be passed on to future generations. In other words, those parts of the code that have undergone the most modification since the chimp-human split are the sequences that most likely shaped humankind.

In November 2004, after months of debugging and optimizing my program to run on a massive computer cluster at the University of California, Santa Cruz, I finally ended up with a file that contained a ranked list of these rapidly evolving sequences. With my mentor David Haussler leaning over my shoulder, I looked at the top hit, a stretch of 118 bases that together became known as human accelerated region 1 (HAR1). Using the U.C. Santa Cruz genome browser, a visualization tool that annotates the human genome with information from public databases, I zoomed in on HAR1. The browser showed the HAR1 sequences of a human, chimp, mouse, rat and chicken—all of the vertebrate species whose genomes had been decoded by then. It also revealed that previous large-scale screening experiments had detected HAR1 activity in two samples of human brain cells, although no scientist had named or studied the sequence yet. We yelled, “Awesome!” in unison when we saw that HAR1 might be part of a gene new to science that is active in the brain.

We had hit the jackpot. The human brain is well known to differ considerably from the chimpanzee brain in terms of size, organization and complexity, among other traits. Yet the developmental and evolutionary mechanisms underlying the characteristics that set the human brain apart are poorly understood. HAR1 had the potential to illuminate this most mysterious aspect of human biology.

We spent the next year finding out all we could about the evolutionary history of HAR1 by comparing this region of the genome in various species, including 12 more vertebrates that were sequenced during that time. It turns out that until humans came along, HAR1 evolved extremely slowly. In chickens and chimps—whose lineages diverged some 300 million years ago—only two of the 118 bases differ, compared with 18 differences between humans and chimps, whose lineages diverged far more recently. The fact that HAR1 was essentially frozen in time through hundreds of millions of years indicates that it does something very important; that it then underwent abrupt revision in humans suggests that this function was significantly modified in our lineage."


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