Dear Brian and Evoldir Members, some time ago, I had asked a question in Evoldir regarding examples of aa indels. The answers were very helpful for me, and I thank everybody. Here is a compilation of the replies. I also put the emails of the people who gave the replies to facilitate further communications. all the best pavlos ----- Many examples of conserved insertions and deletions that are evolutionarily highly significant are described in our published work. Most of the conserved indels reported thus far are for different groups of microorganisms, and information for their sequence alignments and group-specificities can be found at the following website (Microbial Evolution and Molecular Signatures and the references described there. You may also look at the Wikipedia page on *Conseved Signature Indel*s, which describes significance and some general characteristics of the Conserved Indels in protein sequences. Further, as shown in the following work "Singh, B. and Gupta, R. S. (2009) Conserved inserts in the Hsp60 (GroEL) and Hsp70 (DnaK) proteins are essential for cellular growth. *Mol Genet Genomics* 281*,* 361-373", conserved indels in a number of proteins have been shown to be essential for the group of organisms where they are found. Hopefully, the information provided will help clarify the evolutionarry/functional significance of conserved indels. by gupta@mcmaster.ca ----- try the fast-evolving genes for venom proteins in tropical conus snails http://phys.org/news/2012-04-snails-fast-genes-predatory-refine.html also the MHC genes and, as anthropo-selected artifacts, the monoclonal antibodies that have found major medical or industrial success. by marcos.antezana@gmail.com ----- The lentivirus (such as HIV-2, HIV-2, EIAV, FIV) envelope protein grows and shrinks in length over very short time spans. The "variable loops" on the surface of the envelope shield the virus from the host immune system. The longer the lops, the more of the of the conserved parts of the envelope are hidden. But those conserved parts are needed to bind to the host cell surface receptors (CD4 and CCR5 host proteins). You can download alignments of HIV-1 envelope here: http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html Shorter V1-V2 loops are favored at transmission and early in the infection process before the host immune system has created neutralizing antibodies which bind the CD4 receptor-biding site of the envelope. So the loops tend to grow over time in each infected individual and then shorter ones are selected at transmission. Of course this is only on average, and not a solid rule that is always followed. I did a PubMed search for [amino acid insertion] and found these: Diversity and Complexity of the Mouse Saa1 and Saa2 genes. Mori M, Tian G, Ishikawa A, Higuchi K. Exp Anim. 2014;63(1):99-106. PMID: 24521869 A unique *insertion* of low complexity *amino acid* sequence underlies protein-protein interaction in human malaria parasite orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase. Imprasittichail W, Roytrakul S, Krungkrai SR, Krungkrail J. Asian Pac J Trop Med. 2014 Mar;7(3):184-92. doi: 10.1016/S1995-7645(14)60018-3. PMID: 24507637 The 19-*amino acid insertion* in the tumor-associated splice isoform Rac1b confers specific binding to p120 catenin. Orlichenko L, Geyer R, Yanagisawa M, Khauv D, Radisky ES, Anastasiadis PZ, Radisky DC. J Biol Chem. 2010 Jun 18;285(25):19153-61. doi: 10.1074/jbc.M109.099382. Epub 2010 Apr 15. PMID: 20395297 Extension of the hydrolysis spectrum of AmpC beta-lactamase of Escherichia coli due to *amino acid insertion* in the H-10 helix. Mammeri H, Poirel L, Nordmann P. J Antimicrob Chemother. 2007 Sep;60(3):490-4. Epub 2007 Jun 22. Erratum in: J Antimicrob Chemother. 2008 Apr;61(4):971. PMID: 17586561 A 59 *amino acid insertion* increases Ca(2+) sensitivity of rbslo1, a Ca2+ -activated K(+) channel in renal epithelia. Hanaoka K, Wright JM, Cheglakov IB, Morita T, Guggino WB. J Membr Biol. 1999 Dec 1;172(3):193-201. PMID: 10568789 A novel isoform of rat estrogen receptor beta with 18 *amino acid insertion* in the ligand binding domain as a putative dominant negative regular of estrogen action. Maruyama K, Endoh H, Sasaki-Iwaoka H, Kanou H, Shimaya E, Hashimoto S, Kato S, Kawashima H. Biochem Biophys Res Commun. 1998 May 8;246(1):142-7. PMID: 9600083 Neuronal pp60c-src contains a six-*amino acid insertion* relative to its non-neuronal counterpart. Martinez R, Mathey-Prevot B, Bernards A, Baltimore D. Science. 1987 Jul 24;237(4813):411-5. PMID: 2440106 Brian Foley, btf@lanl.gov HIV Databases ----- http://en.wikipedia.org/wiki/Cystic_fibrosis#Cause "CF is caused by a point mutationin the gene cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, ÄF508 , is a deletion (Äsignifying deletion) of three nucleotides [40] that results in a loss of the amino acid phenylalanine(F) at the 508th position on the protein. This mutation accounts for two-thirds (66-70%[18]) of CF cases worldwide and 90% of cases in the United States; however, there are over 1500 other mutations that can produce CF.[41]Although most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an autosomal recessive disease ." suzanne.joneson@gmail.com ----- I don't have an functional indel example for you off the top of my head, but I do have one of the functional cooption of UTR: http://mbe.oxfordjournals.org/cgi/content/abstract/26/12/2679 Best, Joanna, masel@email.arizona.edu ----- Classic (but not uncontroversial) insertion in EF1a at base of opisthokonts by Laura Katz, lkatz@smith.edu ----- Thanks sincerely all of you for your replies pavlos -- Pavlos Pavlidis, PhD Foundation for Research and Technology - Hellas Institute of Molecular Biology and Biotechnology Íikolaou Plastira 100, Vassilika Vouton GR - 711 10, Heraklion, Crete, Greece Pavlos Pavlidis