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The Human SERPIN Repertoire and the Evolution of 14q32.1 and 18q21.3 Gene Clusters

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Abstract

The human genome comprises two large clusters of serine protease–inhibitor genes (SERPINs) originated by duplication events that occurred at different moments of vertebrate evolution. The 14q32.1 cluster includes 11 members, all sharing a similar gene structure to alpha-1-antitrypsin, and the 18q21.3 cluster comprises 10 members, characterized by their homology to chicken ovalbumin. Although the majority of these genes are widespread across mammalian species, some are restrained to certain phylogenetic groups, making the repertoire of each species unique. In primates, events of gene duplication and divergence were associated to the origin of SERPINA2 and SERPINB3. Evolutionary processes specific to the human lineage included the loss of SERPINA13, an ancient gene only kept in primates, and the pseudogenization of SERPINB11, a gene under strong constrains in other species. More recently in humans, natural selection acted in SERPINA2 and SERPINB11 favoring, on one hand, a nonfunctional allele carrying a 2 kb deletion and, on the other, a resurrected gene linked to a novel non-inhibitory function. Considering a possible role of SERPINs in inflammation and immunity, together with the perception of the impact of infectious diseases in the natural history of human populations and other species, raised the hypothesis of an evolution driven by host–pathogens interactions. Overall, gains and losses of genes seem to have had an important adaptive value in the long-term evolution of 14q32.1 and 18q21.3 clusters with current implications in SERPIN activities and effects in human diseases.

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  1. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200-465, Porto, Portugal

    Susana Seixas

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Editors and Affiliations

  1. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margarethe Geiger

  2. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Felix Wahlmüller

  3. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margareta Furtmüller

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Seixas, S. (2015). The Human SERPIN Repertoire and the Evolution of 14q32.1 and 18q21.3 Gene Clusters. In: Geiger, M., Wahlmüller, F., Furtmüller, M. (eds) The Serpin Family. Springer, Cham. https://doi.org/10.1007/978-3-319-22711-5_1

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