ABSTRACT
Matrix metalloproteinases-9 (MMP-9) is an important cancer-associated, zinc-dependent endopeptidase. To investigate the natural selection hypothesis of MMP-9, the orthologous sequences from 12 vertebrates were compared and a molecular evolution analysis was performed. Results suggest that amino acid residues present in the middle region of the protein are more selectively constrained, whereas amino acid residues in the C-terminal region of the MMP-9 protein including exon 13 showed lowest conservation level in non-primate species, suggesting that it is an exon with fast evolving rate compared to the others analyzed. InterProScan analysis shows that exon 13 was located in hemopexin (PEX) domain of MMP-9. Positive selection was detected in PEX domain of MMP-9 protein between human and other species, which indicates that selective pressure may play a role in shaping the function of MMP-9 in the course of evolution.
ABSTRACT
As a secreted glycoprotein that binds to the extracellular domain of Toll-like receptor 4 (TLR4), Lymphocyte Antigen 96 (LY96), also called myeloid differentiation 2 (MD2), is required for the activation of TLR4 by lipopolysaccharide (LPS) and plays an important role in innate immunity, which is the first line of defence against microbial infections. Previous studies have proposed that mammalian toll-like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection. Given the fact that LY96 is highly functionally linked to TLR4, it would be interesting to test whether LY96 is under the intense pressure of natural selection. To investigate the natural selection hypothesis, we compared the coding sequences from 13 vertebrates and evaluated the molecular evolution of LY96 gene in these species. Result shows that natural selection at exon 4 has indeed played a role in shaping the function of LY96 in the course of evolution. In addition to the study of Nakajima, we found the two branch nodes with Ka/Ks ratios greater than 1: the one leading to cow and pig and the other to rabbit and the primates.
ABSTRACT
ObjectiveTo explore the diverse natural and human factors affect the outbreak and spread of avian influenza. We integrated geographic visualization and evolutionary genetics technique to establish a method to track spread of avian influenza in China.MethodsThe sequence data of type A avian flu virus were provided by NCBI Nucleotide and Protein Databases.We transformed the original data to readable structures for Matlab using E-Utilities software.These MATLAB readable structures represented 8 genes of the virus,they are:RNA polymerase B2 (PB2),polymerase B1 (PB1),polymerase A (PA),hemagglutinin (HA),nucleoprotein (NP),ne(ur)al aminidase (NA),matrix (M1),and non-structural ( NS1 ) proteins.Based on these readable structures,we compared Ka/Ks ratio of different virus strains and identified the gene mutation patterns under different selection pressures.Then we selected the gene that exhibited the highest Ka/Ks ratio and performed a phylogenetic analysis by Jukes-Cantor algorithm.Google Earth layer tools were then used to integrate gene variation and geographic transmission information. Results When we compared these 8 virus genes,the NS1,HA and NA were found to exhibit high Ka/Ks ratio and could be seen to represent the transmission capacity of the virus.Among these,the HA gene has the highest Ka/Ks ratio.When we compare the amino acids encoded by the HA gene using clustering analysis,we found that the relationship between H5N1 avian influenza strains since 2003 in Asia made up an evolutionary tree.This evolutionary tree contained 30 nodes ( 14 branch nodes and 16 leaf nodes).All genes were classified into 4 major groups by the first 3 nodes. And these 4 groups exhibit clear geographic patterns in their spread.The impact of geographic factors on the outbreak of avian influenza in China can be ranked as:inland water bodies ( lakes,reservoirs)＞ major railway paths ＞ density of poultry. ConclusionsThe analysis on the dominant strains' gene mutations in China' s H5N1 found that the outbreaks of avian influenza correlate with avian migration and poultry transportation.