Birth and Death in Terminal Complement Pathway

Abstract

AbstractThe cytolytic activity of the membrane attack complex (MAC) has a crucial role in the complement-mediated elimination of pathogens. Terminal complement pathway (TCP) genes encode the proteins that form the MAC. Although the TCP genes are well conserved within most vertebrate species, the early evolution of the TCP genes is poorly understood. Based on the comparative genomic analysis of the early evolutionary history of the TCP homologs, we evaluated four possible scenarios that could have given rise to the vertebrate TCP. Currently available genomic data support a scheme of complex sequential protein domain gains that may be responsible for the birth of the vertebrateC6gene. The subsequent duplication and divergence of this vertebrateC6gene formed theC7, C8α,C8β, andC9genes. Compared to the widespread conservation of TCP components within vertebrates, we discovered thatC9has disintegrated in the genomes of galliform birds. Publicly available genome and transcriptome sequencing datasets of chicken from Illumina short read, PacBio long read, and Optical mapping technologies support the validity of the genome assembly at theC9locus. In this study, we have generated a >120X coverage whole-genome Chromium 10x linked-read sequencing dataset for the chicken and used it to verify the loss of theC9gene in the chicken. We find multiple CR1 (chicken repeat 1) element insertions within and near the remnant exons ofC9in several galliform bird genomes. The reconstructed chronology of events shows that the CR1 insertions occurred afterC9gene loss in an early galliform ancestor. Our study ofC6gene birth in an early vertebrate ancestor andC9gene death in galliform birds provides insights into the evolution of the TCP.