#Diverging sequences how to#

Namely, how far can two sequences diverge while continuously maintaining the same molecular function? What are the temporal patterns of this divergence across billions of years of evolution? And how different protein sites contribute to the long-term divergence between orthologs with the same molecular function? We note that the requirement for the continuous conservation of molecular function is crucial in this context, as multiple examples of convergent evolution and protein engineering demonstrate that the same molecular function, such as catalysis of a specificВ chemical reaction, can in principle be accomplished by proteins with unrelated sequences and evenВ different folds ( Bork et al., 1993 Galperin et al., 1998 Omelchenko et al., 2010). In this work, we focused on a different and currently unaddressed set of questions. For example, the likelihood that two proteins share the same molecular function, given their sequenceВ ( Tian and Skolnick, 2003) or structural ( Wilson et al., 2000) similarity, has been used to investigate the emergence of new protein functions ( Rost, 2002 Conant and Wolfe, 2008), and to perform functional annotations of protein sequences ( Lee et al., 2007 Wilson et al., 2000). Multiple previous studies have investigated the relationship between the conservation of protein molecular function, sequence identity ( Lee et al., 2007 Tian and Skolnick, 2003 Worth et al., 2009) and structural similarity ( Chothia and Lesk, 1986 Wilson et al., 2000).

The Reviewing Editor's assessment is that all the issues have been addressed ( see decision letter).ДЄs proteins evolve from a common ancestor, their sequences and structures diverge from each other ( Chothia and Lesk, 1986 Povolotskaya and Kondrashov, 2010).

#Diverging sequences how to#

Our analysis also reveals different divergence patterns for protein sites with experimentally determined small and large fitness effects of mutations.Д®ditorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. Instead, less than four amino acid types are accepted, on average, per site across orthologous protein sequences. The effective divergence limit (>25% sequence identity) is not primarily due to protein sites universally conserved in all linages. As a result, the sequence and structural similarities between ancient orthologs have not substantially decreased for the past billion years. Our results demonstrate that the decline of sequence and structural similarities between such orthologs significantly slows down after ~1вЂ“2 billion years of independent evolution. We investigate these fundamental questions by characterizing the divergence between ancient protein orthologs with conserved molecular function. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. Functional conservation is known to constrain protein evolution.