Birth and Death in Terminal Complement Pathway

Abstract

The 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 vertebrate C6 gene. The subsequent duplication and divergence of this vertebrate C6 gene formed the C7, C8α, C8β, and C9 genes. Compared to the widespread conservation of TCP components within vertebrates, we discovered that C9 has 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 the C9 locus. 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 the C9 gene in the chicken. We find multiple CR1 (chicken repeat 1) element insertions within and near the remnant exons of C9 in several galliform bird genomes. The reconstructed chronology of events shows that the CR1 insertions occurred after C9 gene loss in an early galliform ancestor. Our study of C6 gene birth in an early vertebrate ancestor and C9 gene death in galliform birds provides insights into the evolution of the TCP.

Concurrent loss of ciliary genesWDR93andCFAP46in phylogenetically distant birds

“…The concurrent loss of WDR93 and CFAP46 in multiple independent lineages of birds, in contrast to conservation across hundreds of other vertebrate species, suggests rapid shifts in selective forces acting on these genes. Loss of genes with host defense functions may result from relaxed selection following a change in pathogen repertoire or invasion strategy [65][66][67]. The ongoing arms race between host and pathogen involves constantly evolving new and complex mechanisms to counter each other and can also cause gene loss [68][69][70].…”

Hitchhiking of bactericidal/permeability-increasing protein-like gene with the fibromelanosis locus in Kadaknath black-bone-chicken

“…In the chicken genome, five BPI -like genes occur near BPI 44 , which works as a bactericidal protein and helps arrest bacterial growth and phagocytosis by neutrophils 45,46 . In chickens, defense against gram-negative bacteria may be especially important as they lack the complement C9 gene required to effectively eliminate pathogens through the Membrane Attack Complex (MAC) formation 47 . Notably, another BBC breed from Korea, YOSK, has signatures of selection at the TLR4 gene involved in detecting gram-negative bacteria 20 .…”

Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds

“…The concurrent loss of WDR93 and CFAP46 in multiple independent lineages of birds, in contrast to conservation across hundreds of other vertebrate species, suggests rapid shifts in selective forces acting on these genes. Loss of genes with host defence functions may result from relaxed selection following a change in pathogen repertoire or invasion strategy [72][73][74]. The ongoing arms race between host and pathogen involves constantly evolving new and complex mechanisms to counter each other and can also cause gene loss [75][76][77].…”