Thursday, January 10, 2013

An acronym in genetics: HAR1 for human accelerated region 1

A recent Special Collector's Edition of Scientific American is entitled What Makes Us Human. The missing question mark suggests that some knowledge exists today on what makes humans evolutionary different from closely related hominids and also from other mammals—despite nearly identical DNA blueprints. A key finding concerning this difference is presented in an exciting article by Katherine Pollard, entitled What Makes Us Different? [1]. Notice the question mark here! The discussed difference: the evolutionary change of a DNA sequence of 118 bases known as human accelerated region 1, HAR1 for short [1-4].

The name for this stretch of letters (bases) refers to the rapid change of letters (18 out of the 118 bases) in the human sequence that occurred over the last 6 million years relative to the conforming chimpanzee sequence. In contrast, comparison of this sequence between chimps, chickens and other vertebrate species over the past 300 million years reveals extremely slow changes (two out of 118 letters differing in the chimp and chicken sequence). Conclusion: the HAR1 genome region remained almost unchanged during most of the vertebrate evolution, while—throughout the dawn of humanity—it quickly acquired new and significant functions in humans, relative to the offsprings of their common chimp-like ancestors.

HAR1 does not directly encode proteins, but RNA. HAR1 is the first documented example of an RNA-encoding sequence that might have undergone positive selection (directional selection), a special mode of natural selection. Recent research suggests that HAR1 has a significant role in the development of a healthy cerebral cortex, the wrinkled outermost brain layer [1].

Many other accelerated genome regions have been predicted and identified, including HAR2, which drives limb (wrist and thumb) development and may be responsible for human dexterity [1,4], as well as a sequence within the FOXP2 gene, which is associated with speech and language development [1,5]. 

Keywords: biology, biostatistics, bioinformatics, mammalian genome, genome scanning, human-specific brain features, evolutionary anthropology.

References and more to explore
[1] Katherine S. Pollard: What Makes Us Different? Scientific American Winter 2013, 22 (1), 30-35.
[2] Katherine S. Pollard et al.: An RNA gene expressed during cortical development evolved rapidly in humans. Nature 2006, 443, 167-172. DOI: 10.1038/nature05113.
[3] Artemy Beniaminov, Eric Westhof and Alain Kroi: Distinctive structures between chimpanzee and human in a brain noncoding RNA. RNA 2008, 14, 1270-1275.
DOI: 10.1261/rna.1054608.
[4] Jeffrey Norris: What Makes Us Human? Studies of Chimp and Human DNA May Tell Us. June 28, 2010 [].
Note: this post also features Katie Pollard, a biostatistician at the University of California in San Francisco, who played an important role in creating mathematical algorithms and software for comparative genomics.
[5] FOXP2: A genetic window into speech and language. [].

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