Adaptive evolution of peptidoglycan recognition protein family regulates the innate signaling against microbial pathogens in vertebrates.

The innate immune system is the first line of defense in vertebrates against microbial pathogens. This defense system depends on the peptidoglycan pathogen recognition of receptors (PGRPs) existing in both invertebrates and vertebrates. Although some studies revealed the structural and functional differences between them, however, the evolutionary history and the selection pressures on these genes during adaptive evolution are poorly understood. In this study, we examined four (PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4) genes of 127 vertebrates' species, conserved across vertebrates to evaluate positive selection pressure drives by adaptive evolution. The codons under positive selection were recognized through likelihood tests by comparing different models based on ω ratios in these genes across the vertebrate species. The positive selection test used two sets of models M1a vs. M2a and M7 vs. M8. The results showed that the test of these genes in M1a vs. M2a was not significant with the likelihood value 2ΔlnL = 0, while the likelihood ratios (2ΔlnL) were 2ΔlnL = 12.386, 2ΔlnL = 4.9283, 2ΔlnL = 24.031, and 2ΔlnL = 103.39 for PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4 in M7 vs. M8, respectively. Our study identified the evidence of robust positive selection for these four genes across the vertebrates. These protuberant changes in PGRPs evolution of vertebrates reveal their role in innate immunity. Our study provides an insight based on PGRP genes to understand the evolution of host and pathogens interaction that leads to the progress of the novel conducts for immune diseases that include proteins linked to the recognition of pathogens.

Bioinformatics Approaches to Explore the Phylogeny and Role of BRCA1 in Breast Cancer.

BRCA1 and BRCA2 are the two major vulnerability genes involved in hereditary breast cancer. BRCA1 gene programs for a tumor suppressor protein that helps in repairing DNA. The purpose of this study was to reveal the position and nature of amino acid residues involved in breast cancer, and it provides a complete characterization of BRCA1 and its evolutionary relationship with 34 selected organisms. The sequences were retrieved from NCBI, and after analyzing them in BLAST, a complete annotation of both types of genes from a human was done; in addition, a phylogenetic analysis was performed from 34 different organisms to study evolutionary relationships of BRCA1. A total of 1080 positions of genes were found in the dataset in which the first 3 were noncoding positions and the remaining were all coding regions. A tree was originated using MEGA that showed strong evolutionary relationships among three orders (Catertiodactyla, carnivore, and primates) of these organisms, which are closely related to each other. All features of wild and mutant proteins were studied by ProtParam. The location and number of alpha helices, beta sheets, coils, strands, and the binding regions, disordered regions were identified using different tools (SOPMA, PHD, and GOR4) and their percentages greatly varied. Our study revealed that the BRCA1 gene involved in cancer development had a weaker selection than those involved in sporadic cancer. Our investigation showed that in mammals, selection acting on human cancer genes drives adaptive variations in behaviors related to organismal fitness, rather than select for biological roles directly linked to cancer.