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Báo cáo y học: "Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals. | Research Open Access Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals JV Chamary and Laurence D Hurst Address Department of Biology and Biochemistry University of Bath Bath BA2 7AY UK. Correspondence Laurence D Hurst. E-mail l.d.hurst@bath.ac.uk Published 16 August 2005 Genome Biology 2005 6 R75 doi 10.1 186 gb-2005-6-9-r75 The electronic version of this article is the complete one and can be found online at http genomebiology.com 2005 6 9 R75 Received 27 April 2005 Revised 8 June 2005 Accepted 20 July 2005 2005 Chamary and Hurst licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http creativecommons.org licenses by 2.0 which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background In mammals contrary to what is usually assumed recent evidence suggests that synonymous mutations may not be selectively neutral. This position has proven contentious not least because of the absence of a viable mechanism. Here we test whether synonymous mutations might be under selection owing to their effects on the thermodynamic stability of mRNA mediated by changes in secondary structure. Results We provide numerous lines of evidence that are all consistent with the above hypothesis. Most notably by simulating evolution and reallocating the substitutions observed in the mouse lineage we show that the location of synonymous mutations is non-random with respect to stability. Importantly the preference for cytosine at 4-fold degenerate sites diagnostic of selection can be explained by its effect on mRNA stability. Likewise by interchanging synonymous codons we find naturally occurring mRNAs to be more stable than simulant transcripts. Housekeeping genes whose proteins are under strong purifying selection are also under the greatest pressure to maintain stability. Conclusion