Characteristic features of the SERA multigene family in the malaria parasite

<jats:title>Abstract</jats:title><jats:p>Serine repeat antigen (SERA) is conserved among species of the genus<jats:italic>Plasmodium</jats:italic>.<jats:italic>Sera</jats:italic>genes form a multigene family and are generally tandemly clustered on a single chromosome. Although all<jats:italic>Plasmodium</jats:italic>species encode multiple<jats:italic>sera</jats:italic>genes, the number varies between species. Among species, the members share similar sequences and gene organization. SERA possess a central papain-like cysteine protease domain, however, in some members, the active site cysteine residue is substituted with a serine. Recent studies implicate this gene family in a number of aspects in parasite biology and induction of protective immune response. This review summarizes the current understanding on this important gene family in several<jats:italic>Plasmodium</jats:italic>species. The<jats:italic>Plasmodium falciparum</jats:italic>(<jats:italic>Pf</jats:italic>)-<jats:italic>sera</jats:italic>family, for example, consists of nine gene members. Unlike other multigene families in<jats:italic>Plasmodium</jats:italic>species,<jats:italic>Pf-sera</jats:italic>genes do not exhibit antigenic variation.<jats:italic>Pf</jats:italic>-<jats:italic>sera5</jats:italic>nucleotide diversity is also low. Moreover, although<jats:italic>Pf-sera5</jats:italic>is highly transcribed during the blood stage of malaria infection, and a large amount is released into the host blood following schizont rupture, in malaria endemic countries the sero-positive rates for Pf-SERA5 are low, likely due to Pf-SERA5 binding of host proteins to avoid immune recognition. As an antigen, the N-terminal 47 kDa domain of Pf-SERA5 is a promising vaccine candidate currently undergoing clinical trials. Pf-SERA5 and Pf-SERA6, as well as<jats:italic>P. berghei</jats:italic>(Pb)-SERA3, and Pb-SERA5, have been investigated for their roles in parasite egress. Two<jats:italic>P. yoelii</jats:italic>SERA, which have a serine residue at the protease active center, are implicated in parasite virulence. Overall, these studies provide insight that during the evolution of the<jats:italic>Plasmodium</jats:italic>parasite, the<jats:italic>sera</jats:italic>gene family members have increased by gene duplication, and acquired various functions that enable the parasite to survive and successfully maintain infection in the host.</jats:p>