Coevolution study of mitochondria respiratory chain proteins: Toward the understanding of proteineprotein interaction Ming Yang a,b , Yan Ge c , Jiayan Wu a , Jingfa Xiao a, * , Jun Yu a, * a CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China b Graduate University of Chinese Academy of Sciences, Beijing 100049, China c College of Biology, China Agricultural University, Beijing 100091, China Received 20 January 2011; revised 8 April 2011; accepted 9 April 2011 Abstract Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of proteineprotein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using “Mirror tree” method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary proteineprotein interaction in intra-complex and the binary proteineprotein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value ¼ 4.4 Â 10 À6 ). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of proteineprotein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Keywords: Coevolution; Respiratory chain proteins; “Mirror tree” method; Supercomplex; Proteineprotein interaction 1. Introduction The protein evolutionary process is affected by many factors, such as temperature, gene localization in the genome, gene expression, and function of proteins. Due to selection pressure, a change in one protein would necessitate compen- satory changes in others (Pazos et al., 1997; Jespers et al., 1999; Goh et al., 2000; Fraser et al., 2004), otherwise, the interaction among proteins is lost as well as its function. This evolutionary process we called “coevolution”, which is critical to almost all biological processes, such as metabolic pathways, signaling cascades and transcription control networks, undergoes adaptive or constructive change without disruption of organism integrity (Pazos and Valencia, 2001; Fraser et al., 2004). Functional correlation proteins (i.e., proteins involve the same metabolic pathway or biological process, or proteins belong to the same structural complex or molecular machine) are ever-present coordinated evolutionary characters. In a living cell, proteins mainly combine with other protein(s) to form protein complex to carry out their functions, especially for structural proteins. As to protein complex system, there are two forms of proteineprotein interactions (Phizicky and Fields, 1995), which refer to binary proteine protein interaction in intra-complex and the binary proteine protein interaction in inter-complex. However, people tend to leave out the existence of the two kinds of interactions in their coevolutional proteins detecting. They prefer to employ one Abbreviations: RC, respiratory chain; CDK, cyclin-dependent kinases; r, correlation coefficient; NADH, reduced nicotinamide adenine dinucleotide; CYTB, cytochrome b; COX, cytochrome c oxidase; SVM, support vector machine. * Corresponding authors. Tel: þ86 10 8299 5384, fax: þ86 10 8299 5401 (J. Xiao); Tel: þ86 10 8299 5357 (J. Yu). E-mail addresses: xiaojingfa@big.ac.cn (J. Xiao), junyu@big.ac.cn (J. Yu). Available online at www.sciencedirect.com Journal of Genetics and Genomics 38 (2011) 201e207 www.jgenetgenomics.org 1673-8527/$ - see front matter Copyright Ó 2011, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved. doi:10.1016/j.jgg.2011.04.003