Sequence diversity at the proximal 14q32.1 SERPIN subcluster: Evidence for natural selection favoring the pseudogenization of SERPINA2

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Susana Seixas (Author) Other; Gianpaolo Suriano (Author) Other; Filipa Carvalho (Author) FMUP; Raquel Seruca (Author) FMUP; Jorge Rocha (Author) FCUP; Anna Di Rienzo (Author) Other

Journal

Title: Molecular Biology and Evolution

Vol. 24

Pages: 587-598

ISSN: 0737-4038

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 18 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-004-C3M

DOI: 10.1093/molbev/msl187

Abstract (EN): The superfamily of serine protease inhibitors (SERPINs) plays a key role in controlling the activity of proteinases in diverse biological processes. alpha 1-antitrypsin (SERPINA1), the most studied member of this family, is encoded by a gene located within the proximal 14q32.1 SERPIN subcluster, together with the highly homologous alpha 1-antitrypsin-like sequence (SERPINA2), which was previously proposed to be a pseudogene. Here, we performed a resequencing study encompassing both SERPINA1 and SERPINA2 as well as the adjacent gene coding for corticosteroid-binding globulin (SERPINA6) in samples from Europe and West Africa. In the African sample, we found that a common haplotype carrying a 2-kb deletion in the SERPINA2 gene is associated with remarkable long-range homozygozity as if it was quickly driven to high frequency by natural selection acting on an advantageous variant. An analysis of the HapMap Phase I data for the Yoruba sample confirmed that variation in this subcluster carries a strong signal of positive selection. We also show that the SERPINA2 gene is expressed and probably encodes a functional SERPIN. Finally, comparisons with orthologous sequences in nonhuman primates showed that SERPINA2 is present in some great apes, but in chimpanzees it was lost by a deletion event independent from that observed in humans. In agreement with the "less is more" hypothesis, we propose that loss of SERPINA2 is an ongoing process associated with a selective advantage during recent primate evolution, possibly because of a role in fertility or in host-pathogen interactions.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12