Tài liệu Báo cáo khoa học: Domain deletions and substitutions in the modular protein evolution doc

Domain deletions and substitutions in the modular protein

evolution

January Weiner 3rd, Francois Beaussart and Erich Bornberg-Bauer

Division of Bioinformatics, School of Biological Sciences, The Westfalian Wilhelms University of Mu¨nster, Germany

Proteins are well known to evolve not only by point

mutations, but also by modular rearrangements [1–

3]. By and large, these rearrangements occur at the

level of domains, which are independent folding units

and have been proposed to represent the unit of

modular evolution [3,4]. Most domains always form

the same combinations; that is, they are always

found next to the same neighbours. For example,

domains found in ribosomal proteins are not found

elsewhere and are present always in the same con￾text. Also, it has been reported that many domains

appear in a very much conserved order (suprado￾mains) [5], and that the frequent occurrence of cer￾tain modular arrangements (arrangements of modules

along a sequence) across phyla is the result of con￾servation [6].

While few domains co-occur with many others at

least once in the same protein, most domains have few

partner domains, or are even always singletons [3,7–9].

Well-known examples of highly linked domains occur￾ring in many different combinations are the P-loop

nucleotide triphosphate hydrolase domain, the epider￾mal growth factor (EGF) domain, the SH3 domain,

the P-kinase domain and the domains involved in the

blood clotting cascade [1,10].

The phenomenon of differential arrangements has

often been termed domain mobility [11]. However,

this term may be misleading as it implies that single

Keywords

domain loss; fission; fusion; protein

domains; protein evolution

Correspondence

E. Bornberg-Bauer, Division of

Bioinformatics, School of Biological

Sciences,The Westfalian Wilhelms

University of Mu¨nster, Schlossplatz 4,

D48149 Mu¨nster, Germany

Fax: +49 251 8321631

Tel: +49 251 8321630

E-mail: [email protected]

(Received 5 December 2005, revised 13

February 2006, accepted 9 March 2006)

doi:10.1111/j.1742-4658.2006.05220.x

The main mechanisms shaping the modular evolution of proteins are

gene duplication, fusion and fission, recombination and loss of frag￾ments. While a large body of research has focused on duplications and

fusions, we concentrated, in this study, on how domains are lost. We

investigated motif databases and introduced a measure of protein simi￾larity that is based on domain arrangements. Proteins are represented as

strings of domains and comparison was based on the classic dynamic

alignment scheme. We found that domain losses and duplications were

more frequent at the ends of proteins. We showed that losses can be

explained by the introduction of start and stop codons which render the

terminal domains nonfunctional, such that further shortening, until the

whole domain is lost, is not evolutionarily selected against. We demon￾strated that domains which also occur as single-domain proteins are less

likely to be lost at the N terminus and in the middle, than at the C ter￾minus. We conclude that fission ⁄fusion events with single-domain

proteins occur mostly at the C terminus. We found that domain substi￾tutions are rare, in particular in the middle of proteins.We also showed

that many cases of substitutions or losses result from erroneous annota￾tions, but we were also able to find courses of evolutionary events where

domains vanish over time. This is explained by a case study on the bac￾terial formate dehydrogenases.

Abbreviations

Domain ID, domain identification number; EGF, epidermal growth factor; FDHF, formate dehydrogenase H.

FEBS Journal 273 (2006) 2037–2047 ª 2006 The Authors Journal compilation ª 2006 FEBS 2037