Документ взят из кэша поисковой машины. Адрес оригинального документа : http://mccmb.belozersky.msu.ru/2013/abstracts/abstracts/193.pdf Дата изменения: Mon Jun 3 05:06:56 2013 Дата индексирования: Thu Feb 27 21:07:53 2014 Кодировка:

Strong negative selection on CpG dinucleotides in the human gen ome: a compar ison of de novo and in herited mutation rates Serge y A. Spirin
Department of Mathematical Methods in Biology, Belozersky Institute, Moscow State University, sas@belozersky.msu.ru

Sofya A. Medvedeva
Department of Bioengineering and Bioinformatics, Moscow State University , sof.medv@gmail.com

Alexa nder Y. Pa nc hin
Institute for Information Transmission Proble ms, Russian Academy of Science, alexpanchin@yahoo.com

Andre y V. Alexeevs ki
Department of Mathematical Methods in Biology, Belozersky Institute, Moscow State University, , aba@belozersky.msu.ru

Yuri V. Pa nc hin
Institute for Information Transmission Problems, Russian Academy of Sciences , ypanchin@yahoo.com

In a recent article Kong et al.1 meas ured de novo mutatio ns rates in 78 huma n parent-offspring trios. The reported rate o f de novo C to T (a nd also G to A) mutatio ns is 18 ti mes hi gher in CpG sites tha n i n non-Cp G sites and this difference is greater than previo us esti mat es. De novo muta tions in pare nt-o ffspring trios seem to be the best available representation o f muta tions that have not passed through long- ter m filters of na tural selection. Other sources used to ob tai n muta tion data s uc h as SNPs or cross -species variations are infl ue nced by na tural selection to a muc h greater exte nt beca use the y provide infor matio n o n mutatio ns that were probably passed down thro ugh ma ny ge nerations. We co mpared the de novo mutatio n data ob tained b y Ko ng e t. al and muta tion da ta derived fro m a set o f inherited (trans mi tted) mutatio ns tha t resulted i n huma n single nucleotide polymorp his ms (SNPs). The direction o f these inherited muta tions was established by reconstruc ting the a ncestral states of SNPs usi ng the alignme nts of hu ma n, c hi mp a nd oranguta n ge no mes. T he co mparison o f these two muta tion da tasets adds new prospective to


the results obtai ned by Ko ng et al. Bo th de novo and i nherited muta tion da tasets indicate a trend towards the decrease of G+C co nte nt i n the huma n geno me, b ut CpG di nucleotides are accumulated according to i nherited mutatio ns data, yet lost according to de novo muta tions data. B y co mparing muta tion da tasets we were able to estimate the fractio n of CpG dinucleotides experiencing the pressure o f stabilizing selection. Our a nalysi s supports the hypo thesis that na tural selection strongl y favors CpG preservation o n the geno me scale in huma ns. Co mp utatio ns based on dataset co mparisons suggest that a t least 50% of Cp G dinucleotides in the huma n ge no me are under the pressure of stabilizing selection. T his hypo thesis is also supported by additional a nalysis of the allele freque ncies of novel variants resulting fro m gained a nd lost Cp G dinucleotides. 1. Kong, A. et al. (2012) Rate of de novo muta tions a nd the i mpor tance o f father's age to disease risk, Nature, 488:471-475