Sequence, structure, and evolution of a complete human olfactory receptor gene cluster.

Area of Science:

• Genomics
• Human Genetics
• Olfactory Receptor Research

Background:

• The olfactory receptor (OR) gene cluster on human chromosome 17p13.3 is crucial for smell perception.
• Understanding the genomic organization and evolutionary history of OR clusters provides insights into chemosensory diversity.

Purpose of the Study:

• To perform automated DNA sequencing of the human chromosome 17p13.3 OR gene cluster.
• To identify and characterize OR coding regions, pseudogenes, and regulatory elements within the cluster.
• To investigate the genomic structure and evolutionary implications of this OR gene cluster.

Main Methods:

• Mixed shotgun automated DNA sequencing of a 412 kb genomic region.
• Sequence analysis to identify OR coding regions, pseudogenes, and repetitive elements.
• Comparative analysis of DNA sequences to determine gene structure and identify potential regulatory sites.

Main Results:

• Sequenced 412 kb of the 17p13.3 OR cluster, identifying 17 OR coding regions (6 pseudogenes) and discovering 6 novel coding regions.
• Identified a common gene structure with intronless coding regions and upstream noncoding exons, along with potential gene control regions (Olf-1 sites).
• Found four extensive CpG islands, one evolved from a pseudogene, and a flanking unidentified open reading frame (C17orf2). Approximately 60% of the sequence comprises interspersed repetitive elements, predominantly LINE repeats.

Conclusions:

• The human chromosome 17p13.3 OR cluster exhibits a complex genomic organization with intermixed gene families and random orientations.
• The identified gene structures, regulatory elements, and repetitive sequences suggest a history of complex evolutionary events shaping this region.
• This detailed genomic characterization provides a foundation for further research into OR gene function and evolution.