MERS-CoV Origin,Evolution And Its Relationship With The Host Based On Bioinformatics Analysis

Coronavirus is a type of virus that exists widely and causes serious damage to humans and livestock.The genome is composed of about 30 Kb base and is the largest in all RNA viruses.The Middle East Respiratory Syndrome Coronavirus(MERS-CoV),discovered firstly in Saudi Arabia in 2012,can cause severe respiratory disease with clinical manifestations of acute respiratory distress syndrome,renal failure and even death.Therefore,MERS has become a newly type of coronavirus threatening the health and safety of human life.However,so far,it has not been studied clearly for the origin,evolution,and host of MERS-CoV.In this study,we investigated phylogenetic relationships between MERS-CoV and other coronavirus protein of S,M,E and N by constructing phylogenetic tree.The 190 strains of MERS-CoV strains were divided into 39 categories according to their geographical.We selected representative strains and constructed the phylogenetic tree with the whole genome sequence was to explore the virus origin and evolution.RDP was used to analyze the MERS-CoV recombination,and on this basis,the evolution pattern of the structural protein gene of the virus was analyzed.A codon bias analysis was performed on 9 genes of the MERS-CoV prototype strain to investigate the virus codon usage pattern and its relationship with the host;the differences of codon usage patterns between MERS-CoV and other viruses of coronavirus were compared to study the variation of codon usage of the coronavirus virus.The main results of this paper are as follows:1.Phylogenetic analysis of MERS-CoV and 19 other coronaviruses was performed by MEGA software.The result indicated that MERS-CoV is a new species different from other virus of coronavirus.MERS-CoV is different from three groups of coronavirus and the SARS coronavirus.Therefore,we think that MERS-CoV belongs to fifth coronaviruses.At the same time,phylogenetic analysis was performed on MERS-CoV genome sequences.The results showed that the evolution of MERS-CoV was closely related to the outbreak time and distribution area of the virus.The closer the outbreak time and the geographical distance,the closer the virus genetic relationship is,and the evolution of virus is also related to it s host.Combined and patient travel history and some literature,it is further conjectured that the virus was initially spread from Bisa to Riyadh and then spread to other Saudi cities by these two places.The strain in China is probably traced back to the Jeddah region of Saudi Arabia.2.Recombination analysis of the MERS-CoV virus was performed by RDP.The results showed that there was a most reliable recombinant signal in S gene fragment between MERS-CoV and its near-origin bat strain.Combined with literature data,we speculated that the virus originated from bats and infect ed humans through dromedary eventually.By studying the evolutionary pattern of viral structural protein genes,the results showed that S and N genes undergo negative selection,and the E and M protein genes change from positive selection to negative selection evolution.We speculated that these two genes played an important role in the evolution of the virus adapted to the host.3.The analysis of codon preference of MERS-CoV showed that the virus codon usage bias was a little slight and preferred codons ending with A and T.Finally,the 19 major preference codons for MERS-CoV were defined.According to the neutral drawing analysis and ENC-plot analysis,codon bias is mainly affected by selection pressure in the MERS-CoV genome.Through comparison with the other five kinds of biological codon usage frequency,it was found that in its host system,the MERS-CoV codon usage frequency is relatively close to humans,which may be a reason why the virus easily infects people.In prokaryotic expression system,it was more close to yeast,so eukaryotic systems such as yeast may be suitable as MERS-CoV exogenous expression vectors.4.Comparing the codon usage of MERS-CoV with some other coronavirus,it was showed that the coronavirus is highly specific in the use of codons,which further indicated that the virus of the family has a strict conservatism in the process of long-term evolution.Through cluster analysis,we found that the use of codons didn't reflect the real evolutionary system of species.We hypothesized that codon usage might be traced to different evolutionary pathways in the way of species evolution.