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Scientists document complex genomic events leading to the birth of new genes

py in humans but only a single copy in all other species tested. They then turned their attention to the gene that exhibited the most dramatic of these duplications: RanBP2. RanBP2 is the largest protein found at the nuclear pore complex, helping to regulate nucleic acid and protein traffic in and out of the nucleus. The corresponding gene is present in all sequenced animal genomes but not in other eukaryotes, such as plants or fungi.

The new gene family characterized by Dr. Bork and his colleagues was largely derived from RanPB2, but it had also acquired a domain from the neighboring GCC2 gene, whose protein product contains a GRIP domain that localizes intracellularly to the trans-Golgi network. The new gene family, spanning approximately 10% of human chromosome 2, was named RGP (for RanBP2-like, GRIP domain-containing proteins).

By analyzing the gene order around the RanBP2 and GCC2 genes, Bork's team was able to reconstruct the genomic rearrangements leading to the formation of the ancestral RGP locus. These events included a combination of duplication, inversion, partial deletion, and domain acquisition, and this was followed by a series of duplications that gave rise to each RGP family member. A total of eight RGP-family genes were identified, all of which are believed to be fully functional.

To demonstrate that RGP-family genes have functions that are significantly divergent from those of RanBP2, Bork and his co-workers examined the subcellular localization of one of the RGP-family isoforms. In contrast to RanBP2, which is found exclusively at the nuclear envelope, this RGP-family protein was detected in discrete cytoplasmic locations, thereby confirming its functional divergence from RanBP2.

Identifying and characterizing genes that are responsible for primate or human distinctiveness has been a major challenge to scientists. However, this work by Bork and his colleagues should further enable studies focused on the molecular b
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Source:Cold Spring Harbor Laboratory


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