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Citation for Study 15931

Citation title: "Molecular evolution of NASP and conserved histone H3/H4 transport pathway".

Study name: "Molecular evolution of NASP and conserved histone H3/H4 transport pathway".

This study is part of submission 15931 (Status: Published).

Citation

Nabeel-shah S., Ashraf K., Pearlman R.E., & Fillingham J.S. 2014. Molecular evolution of NASP and conserved histone H3/H4 transport pathway. BMC Evolutionary Biology, 14(139).

Authors

• Nabeel-shah S.
• Ashraf K.
• Pearlman R.E.
• Fillingham J.S.

Abstract

Background: NASP is an essential protein in mammals that functions in histone transport pathways and maintenance of a soluble reservoir of histones H3/H4. NASP has been studied exclusively in Opisthokonta lineages where some functional diversity has been reported. In humans, growing evidence implicates NASP miss-regulation in the development of a variety of cancers. Although a comprehensive phylogenetic analysis is lacking, NASP-family proteins that possess four TPR motifs are thought to be widely distributed across eukaryotes. Results: We characterize the molecular evolution of NASP by systematically identifying putative NASP orthologs across diverse eukaryotic lineages ranging from excavata to those of the crown group. We detected extensive silent divergence at the nucleotide level suggesting the presence of strong purifying selection acting at the protein level. We also observed a selection bias for high frequencies of acidic residues which we hypothesize is a consequence of their critical function(s), further indicating the role of functional constraints operating on NASP evolution. Our data indicate that TPR1 and TPR4 constitute the most rapidly evolving functional units of NASP and may account for the functional diversity observed among well characterized family members. We also show that NASP paralogs in ray-finned fish have different genomic environments with clear differences in their GC content and have undergone significant changes at the protein level suggesting functional diversification. Conclusion: We draw four main conclusions from this study. First, wide distribution of NASP throughout eukaryotes suggests that it was likely present in the last eukaryotic common ancestor (LECA) possibly as an important innovation in the transport of H3/H4. Second, strong purifying selection operating at the protein level has influenced the nucleotide composition of NASP genes. Further, we show that selection has acted to maintain a high frequency of functionally relevant acidic amino acids in the region that interrupts TPR2. Third, functional diversity reported among several well characterized NASP family members can be explained in terms of quickly evolving TPR1 and TPR4 motifs. Fourth, NASP fish specific paralogs have significantly diverged at the protein level with NASP2 acquiring a NNR domain.

Keywords

NASP, H3/H4 transport, Hif1, N1/N2, molecular evolution, chromatin, phylogenetics, SHNi-TPR, histone chaperone

External links

• DOI: 10.1186/1471-2148-14-139
• Other URL: http://www.biomedcentral.com/1471-2148/14/139

About this resource

• Canonical resource URI: http://purl.org/phylo/treebase/phylows/study/TB2:S15931
• Other versions: Nexus NeXML
• Show BibTeX reference

  		@ARTICLE{TreeBASE2Ref23301,
  	 author = {Syed  Nabeel-Shah and Kanwal  Ashraf and Ronald E Pearlman and Jeffrey S Fillingham},
  	 title = {Molecular evolution of NASP and conserved histone H3/H4 transport pathway},
  	 year = {2014},
  	 keywords = {NASP, H3/H4 transport, Hif1, N1/N2, molecular evolution, chromatin, phylogenetics, SHNi-TPR, histone chaperone},
  	 doi = {10.1186/1471-2148-14-139},
  	 url = {http://www.biomedcentral.com/1471-2148/14/139},
  	 pmid = {},
  	 journal = {BMC Evolutionary Biology},
  	 volume = {14},
  	 number = {139},
  	 pages = {},
  	 abstract = {Background: NASP is an essential protein in mammals that functions in histone transport pathways and maintenance of a soluble reservoir of histones H3/H4. NASP has been studied exclusively in Opisthokonta lineages where some functional diversity has been reported. In humans, growing evidence implicates NASP miss-regulation in the development of a variety of cancers. Although a comprehensive phylogenetic analysis is lacking, NASP-family proteins that possess four TPR motifs are thought to be widely distributed across eukaryotes.
  Results: We characterize the molecular evolution of NASP by systematically identifying putative NASP orthologs across diverse eukaryotic lineages ranging from excavata to those of the crown group. We detected extensive silent divergence at the nucleotide level suggesting the presence of strong purifying selection acting at the protein level. We also observed a selection bias for high frequencies of acidic residues which we hypothesize is a consequence of their critical function(s), further indicating the role of functional constraints operating on NASP evolution. Our data indicate that TPR1 and TPR4 constitute the most rapidly evolving functional units of NASP and may account for the functional diversity observed among well characterized family members. We also show that NASP paralogs in ray-finned fish have different genomic environments with clear differences in their GC content and have undergone significant changes at the protein level suggesting functional diversification.
  Conclusion: We draw four main conclusions from this study. First, wide distribution of NASP throughout eukaryotes suggests that it was likely present in the last eukaryotic common ancestor (LECA) possibly as an important innovation in the transport of H3/H4. Second, strong purifying selection operating at the protein level has influenced the nucleotide composition of NASP genes. Further, we show that selection has acted to maintain a high frequency of functionally relevant acidic amino acids in the region that interrupts TPR2. Third, functional diversity reported among several well characterized NASP family members can be explained in terms of quickly evolving TPR1 and TPR4 motifs. Fourth, NASP fish specific paralogs have significantly diverged at the protein level with NASP2 acquiring a NNR domain.}
  }
  		

• Show RIS reference

  		TY  - JOUR
  ID  - 23301
  AU  - Nabeel-Shah,Syed 
  AU  - Ashraf,Kanwal 
  AU  - Pearlman,Ronald E
  AU  - Fillingham,Jeffrey S
  T1  - Molecular evolution of NASP and conserved histone H3/H4 transport pathway
  PY  - 2014
  KW  - NASP
  KW  - H3/H4 transport
  KW  - Hif1
  KW  - N1/N2
  KW  - molecular evolution
  KW  - chromatin
  KW  - phylogenetics
  KW  - SHNi-TPR
  KW  - histone chaperone
  UR  - http://www.biomedcentral.com/1471-2148/14/139
  N2  - Background: NASP is an essential protein in mammals that functions in histone transport pathways and maintenance of a soluble reservoir of histones H3/H4. NASP has been studied exclusively in Opisthokonta lineages where some functional diversity has been reported. In humans, growing evidence implicates NASP miss-regulation in the development of a variety of cancers. Although a comprehensive phylogenetic analysis is lacking, NASP-family proteins that possess four TPR motifs are thought to be widely distributed across eukaryotes.
  Results: We characterize the molecular evolution of NASP by systematically identifying putative NASP orthologs across diverse eukaryotic lineages ranging from excavata to those of the crown group. We detected extensive silent divergence at the nucleotide level suggesting the presence of strong purifying selection acting at the protein level. We also observed a selection bias for high frequencies of acidic residues which we hypothesize is a consequence of their critical function(s), further indicating the role of functional constraints operating on NASP evolution. Our data indicate that TPR1 and TPR4 constitute the most rapidly evolving functional units of NASP and may account for the functional diversity observed among well characterized family members. We also show that NASP paralogs in ray-finned fish have different genomic environments with clear differences in their GC content and have undergone significant changes at the protein level suggesting functional diversification.
  Conclusion: We draw four main conclusions from this study. First, wide distribution of NASP throughout eukaryotes suggests that it was likely present in the last eukaryotic common ancestor (LECA) possibly as an important innovation in the transport of H3/H4. Second, strong purifying selection operating at the protein level has influenced the nucleotide composition of NASP genes. Further, we show that selection has acted to maintain a high frequency of functionally relevant acidic amino acids in the region that interrupts TPR2. Third, functional diversity reported among several well characterized NASP family members can be explained in terms of quickly evolving TPR1 and TPR4 motifs. Fourth, NASP fish specific paralogs have significantly diverged at the protein level with NASP2 acquiring a NNR domain.
  L3  - 10.1186/1471-2148-14-139
  JF  - BMC Evolutionary Biology
  VL  - 14
  IS  - 139
  ER  -