Analysis Of Host-Specific Microsatellites Landscape In Severe Acute Respiratory Syndrome-Related Coronavirus Genome

Microsatellite is a sort of DNA or RNA repeats of 2 to 6 bases,also known as Simple Sequence Repeats(SSR).Microsatellite sequences are widely distributed in the non-coding region,coding region and intergenic region of eukaryotes and prokaryotic genomes.Microsatellite sequences are highly variable and diverse,so microsatellite sequences are widely used as a molecular marker in applications such as identification,paternity testing,and gene-association analysis between populations or individuals.Besides,microsatellites also play an important physiological role in living organisms and more than 40 forms of human congenital disease are caused by changes in the number of microsatellite repeats.At present,the research on microsatellites mainly focuses on prokaryotes and eukaryotes,but the research in the viral genome is still very limited.The Severe Acute Respiratory Syndrome-Related Coronavirus(SARS-CoV)caused a global SARS outbreak in 2002-2003 with 774 deaths in 37 countries.Bats are the natural host of SARS-CoV which infected to civets at the end of 2002.It eventually led to outbreaks of SARS-CoV among the population.The short outbreak time and high infectious rate may be related to the ability of microsatellite of quick adaptment to the environment in some speices.In this paper,SARSr-CoV infecting with bats.civets and human beings are used.From microsatellite,combined with statistical and computerized methods,the microsatellite distributions are analyzed and revealed.This article mainly has the following two aspects:Analysis of microsatellite sequences in SARS-CoV genome sequences(Chapter 2)In this study,we downloaded 165 SARS-CoV genome sequences from the NCBI Genbank database and divided them into three groups according to their host.The following results were obtained:(1)The similarity of genomic sequences was high.SARS-CoV infected with different hosts had short evolutionary time;(2)There are differences in the number distribution of microsatellites between groups.The number of mononucleotide microsatellites in civets SARSr-CoV are the lowest quantity in three groups;Dinucleotide microsatellites in bats SARS-CoV genome sequences are the higest quantity in three groups while dinucleotide microsatellites in civets and humans are almost equal;(3)Microsatellites of different types of repeat units differ much more.One of the main differences is reflected in mononucleotide microsatellite,indicating that mononucleotide microsatellites may be the key to promoting evolution.Dinucleotide microsatellites are very stable,indicating that type dinucleotide microsatellites may play an important physiological role.Trinucleotide microsatellites in humans/civets SARS-CoV are highly consistent,and bats are quite different from them,and there is its unique microsatellite.Indicating that SARS may have evolved from a small population of bat SARSr-CoVs.while the large number of evolved SARSr-CoVs in bats are well prepared for cross-host transmission.Analysis of microsatellite host-specific distribution in SARS-CoV genome(Chapter 3)The number and type of microsatellites in the SARS-CoV genome sequence were analyzed in Chapter 2,but the analysis failed to obtain detailed information on the microsatellite distribution.In Chapter 3,a C ++ software developed by our research group was used to further analyze the three groups of S ARSr-CoVs infected with different hosts to obtain microsatellite distribution patterns in different regions of the SARSr-CoV genome.The results showed that microsatellites were nonrandomly distributed at different locations in the genome.The distribution of microsatellites in the genome of the virus was in a region-specific manner.The distribution of microsatellites in the same region of SARSr-CoV infected with different hosts was host-specific.(1)Mononucleotide microsatellites are mostly distributed in the S gene region,and show obvious host specificity.There is no microsatellite in the bats SARSr-CoV at the microsatellite loci of the S gene region,and there are some perfect microsatellites and some imperfect microsatellites in the civets SARSr-CoV,while humans SARSr-CoV has perfect microsatellite at all.S gene express the protein in the invasion of cells to play a role in receptor recognition and cytolysis.(2)Dinucleotide microsatellites are mostly distributed in the ORFlab gene region,and there is not a large number difference of dinucleotide microsatellites in the same region among the three groups of viruses.This region is responsible for producing the required RNA helicases in the normal physiological processes of the virus,RNA polymerase and protease and other important substances,in order to ensure the survival of individual virus,this region must be conservative,so dinucleotide microsatellites in this region did not occur a larger mutation.(3)The trinucleotide microsatellites exist in the same area in the humans/civet genome sequences,but the distribution of the trinucleotide microsatellites in the genomic region is more dispersed and average.It is speculated that the trinucleotide microsatellites are evolving.Trinucleotide microsatellites can provide a rich gene pool for the bat SARSr-CoV population,and abundant gene pools make it possible to cross-host from bats to civets or humans.