title: Analysis of coevolution in nonstructural proteins of chikungunya virus.
abstract: BACKGROUND
  RNA viruses are characterized by high rate of mutations mainly due to the lack of proofreading repair activities associated with its RNA-dependent RNA-polymerase (RdRp). In case of arboviruses, this phenomenon has lead to the existence of mixed population of genomic variants within the host called quasi-species. The stability of strains within the quasi-species lies on mutations that are positively selected which in turn depend on whether these mutations are beneficial in either or both hosts. Coevolution of amino acids (aa) is one phenomenon that leads to establishment of favorable traits in viruses and leading to their fitness.
  
  
  RESULTS
  Fourteen CHIKV clinical samples collected over three years were subjected to RT-PCR, the four non-structural genes amplified and subjected to various genetic analyses. Coevolution analysis showed 30 aa pairs coevolving in nsP1, 23 aa pairs coevolving in nsP2, 239 in nsP3 and 46 aa coevolving pairs in nsP4 when each non-structural protein was considered independently. Further analysis showed that 705 amino acids pairs of the non-structural polyproteins coevolved together with a correlation coefficient of ≥0.5. Functional relevance of these coevolving amino acids in all the nonstructural proteins of CHIKV were predicted using Eukaryotic Linear Motifs (ELMs) of human.
  
  
  CONCLUSIONS
  The present study was undertaken to study co-evolving amino acids in the non-structural proteins of chikungunya virus (CHIKV), an important arbovirus. It was observed that several amino acids residues were coevolving and shared common functions.
authors.affiliation: Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Jain
authors.affiliation: Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
authors.forename: Kalika
authors.initials: K
authors.lastname: Mathur
authors.affiliation: Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
authors.forename: Jatin
authors.initials: J
authors.lastname: Shrinet
authors.affiliation: Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Bhatnagar
authors.affiliation: Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India. sujatha@icgeb.res.in.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Sunil
mesh_terms: D000596:Amino Acids / Q000235:genetics; D065632:Chikungunya Fever / Q000821:virology*; D002646:Chikungunya virus / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D006801:Humans; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*
chemical_list: D000596:Amino Acids; D017361:Viral Nonstructural Proteins
keywords: Chikungunya virus; Coevolution; Eukaryotic linear motifs; Nonstructural proteins