title: Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution.
abstract: BACKGROUND
  The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus.
  
  
  RESULTS
  Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV.
  
  
  CONCLUSIONS
  To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV.
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. izzanasrullah@gmail.com.
authors: Izza
authors: I
authors: Nasrullah
authors: Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, 53700, Pakistan. azeem@cemb.edu.pk.
authors: Azeem M
authors: AM
authors: Butt
authors: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, F-37380, France. shifa.tahir@tours.inra.fr.|CNRS, UMR7247, F-37380, Nouzilly, France. shifa.tahir@tours.inra.fr.|Université François Rabelais de Tours, Tours, F-37380, France. shifa.tahir@tours.inra.fr.
authors: Shifa
authors: S
authors: Tahir
authors: Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, 53700, Pakistan. idreeskhan@cemb.edu.pk.
authors: Muhammad
authors: M
authors: Idrees
authors: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People's Republic of China. tong.yigang@gmail.com.
authors: Yigang
authors: Y
authors: Tong
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002685:Chiroptera / Q000821:virology; D003062:Codon; D019143:Evolution, Molecular; D016679:Genome, Viral; D006801:Humans; D029024:Marburgvirus / Q000235:genetics*; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D003062:Codon