Independent Effects of Alternative Splicing and Structural Constraint on the Evolution of Mammalian Coding Exons

被引:12
作者
Chen, Feng-Chi [1 ,2 ,3 ]
Pan, Chia-Lin [1 ]
Lin, Hsuan-Yu [1 ]
机构
[1] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Miaoli County, Taiwan
[2] Natl Chiao Tung Univ, Dept Life Sci, Hsinchu, Taiwan
[3] Chinese Med Univ, Dept Dent, Taichung, Taiwan
关键词
alternative splicing; intrinsically disordered region; nonsynonymous to synonymous substitution rate ratio; SELECTION PRESSURE; PROTEINS; SEQUENCE; MOUSE; PREDICTION; PATTERNS; SUBJECT; REGIONS;
D O I
10.1093/molbev/msr182
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alternative splicing (AS) is known to significantly affect exon-level protein evolutionary rates in mammals. Particularly, alternatively spliced exons (ASEs) have a higher nonsynonymous-to-synonymous substitution rate (dN/dS) ratio than constitutively spliced exons (CSEs), possibly because the former are required only occasionally for normal biological functions. Meanwhile, intrinsically disordered regions (IDRs), the protein regions lacking fixed 3D structures, are also reported to have an increased evolutionary rate due to lack of structural constraint. Interestingly, IDRs tend to be located in alternative protein regions. Yet which of these two factors is the major determinant of the increased dN/dS in mammalian ASEs remains unclear. By comparing human-macaque and human-mouse one-to-one orthologous genes, we demonstrate that AS and protein structural disorder have independent effects on mammalian exon evolution. We performed analyses of covariance to demonstrate that the slopes of the (dN/dS-percentage of IDR) regression lines differ significantly between CSEs and ASEs. In other words, the dN/dS ratios of both ASEs and CSEs increase with the proportion of IDR (PIDR), whereas ASEs have higher dN/dS ratios than CSEs when they have similar PIDRs. Since ASEs and IDRs may less frequently overlap with protein domains (which also affect dN/dS), we also examined the correlations between dN/dS ratio and exon type/PIDR by controlling for the density of protein domain. We found that the effects of exon type and PIDR on dN/dS are both independent of domain density. Our results imply that nature can select for different biological features with regard to ASEs and IDRs, even though the two biological features tend to be localized in the same protein regions.
引用
收藏
页码:187 / 193
页数:7
相关论文
共 31 条
[1]   Comparing Models of Evolution for Ordered and Disordered Proteins [J].
Brown, Celeste J. ;
Johnson, Audra K. ;
Daughdrill, Gary W. .
MOLECULAR BIOLOGY AND EVOLUTION, 2010, 27 (03) :609-621
[2]   Evolutionary rate heterogeneity in proteins with long disordered regions [J].
Brown, CJ ;
Takayama, S ;
Campen, AM ;
Vise, P ;
Marshall, TW ;
Oldfield, CJ ;
Williams, CJ ;
Dunker, AK .
JOURNAL OF MOLECULAR EVOLUTION, 2002, 55 (01) :104-110
[3]   Alternatively and constitutively spliced exons are subject to different evolutionary forces [J].
Chen, FC ;
Wang, SS ;
Chen, CJ ;
Li, WH ;
Chuang, TJ .
MOLECULAR BIOLOGY AND EVOLUTION, 2006, 23 (03) :675-682
[4]   Different alternative splicing patterns are subject to opposite selection pressure for protein reading frame preservation [J].
Chen, Feng-Chi ;
Chuang, Trees-Juen .
BMC EVOLUTIONARY BIOLOGY, 2007, 7
[5]   Opposite evolutionary effects between different alternative splicing patterns [J].
Chen, Feng-Chi ;
Chaw, Shu-Miaw ;
Tzeng, Yun-Huei ;
Wang, Sheng-Shun ;
Chuang, Trees-Juen .
MOLECULAR BIOLOGY AND EVOLUTION, 2007, 24 (07) :1443-1446
[6]   Identification and evolutionary analysis of novel exons and alternative splicing events using cross-species EST-to-genome comparisons in human, mouse and rat [J].
Chen, Feng-Chi ;
Chen, Chuang-Jong ;
Ho, Jar-Yi ;
Chuang, Trees-Juen .
BMC BIOINFORMATICS, 2006, 7 (1)
[7]   PreDisorder: ab initio sequence-based prediction of protein disordered regions [J].
Deng, Xin ;
Eickholt, Jesse ;
Cheng, Jianlin .
BMC BIOINFORMATICS, 2009, 10
[8]   MUSCLE: multiple sequence alignment with high accuracy and high throughput [J].
Edgar, RC .
NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :1792-1797
[9]   Fast rate of evolution in alternatively spliced coding regions of mammalian genes [J].
Ermakova, EO ;
Nurtdinov, RN ;
Gelfand, MS .
BMC GENOMICS, 2006, 7 (1)
[10]   The Pfam protein families database [J].
Finn, Robert D. ;
Mistry, Jaina ;
Tate, John ;
Coggill, Penny ;
Heger, Andreas ;
Pollington, Joanne E. ;
Gavin, O. Luke ;
Gunasekaran, Prasad ;
Ceric, Goran ;
Forslund, Kristoffer ;
Holm, Liisa ;
Sonnhammer, Erik L. L. ;
Eddy, Sean R. ;
Bateman, Alex .
NUCLEIC ACIDS RESEARCH, 2010, 38 :D211-D222