Evidence for turnover of functional noncoding DNA in mammalian genome evolution.

@article{citeulike:1097343, abstract = {The vast majority of the mammalian genome does not code for proteins, and a fundamental question in genomics is: What proportion of the noncoding mammalian genome is functional? Most attempts to address this issue use sequence comparisons between highly diverged mammals such as human and mouse to identify conservation due to negative selection. But such comparisons will underestimate the true proportion of functional noncoding DNA if there is turnover, if patterns of negative selection change over time. Here we test whether the inferred level of negative selection differs between different pairwise species comparisons. Using a multiple alignment of more than a megabase of contiguous sequence from eight mammalian species, we find a strong negative relationship between inferred levels of negative selection and pairwise divergence using 21 pairwise comparisons. This result suggests that there is a high rate of turnover of functional noncoding elements in the mammalian genome, so measures of functional constraint based on human-mouse comparisons may seriously underestimate the true value.}, address = {Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyv\"{a}gen 18D, 752 36 Uppsala, Sweden. n.g.smith@lancaster.ac.uk <n.g.smith@lancaster.ac.uk>}, author = {Smith, N. G. and Brandstr\"{o}m, M. and Ellegren, H. }, citeulike-article-id = {1097343}, comment = {do some alignments. estimate two parameters of interest: proportion of sites under purifying selection and the turnover rate}, doi = {10.1016/j.ygeno.2004.07.012}, issn = {0888-7543}, journal = {Genomics}, keywords = {turnover}, month = {November}, number = {5}, pages = {806--813}, posted-at = {2007-02-09 20:07:10}, priority = {0}, title = {Evidence for turnover of functional noncoding DNA in mammalian genome evolution.}, url = {http://dx.doi.org/10.1016/j.ygeno.2004.07.012}, volume = {84}, year = {2004} }

TY - JOUR ID - citeulike:1097343 L3 - citeulike-article-id:1097343 TI - Evidence for turnover of functional noncoding DNA in mammalian genome evolution. JF - Genomics VL - 84 IS - 5 SP - 806 EP - 813 AD - Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18D, 752 36 Uppsala, Sweden. n.g.smith@lancaster.ac.uk <n.g.smith@lancaster.ac.uk> SN - 0888-7543 N2 - The vast majority of the mammalian genome does not code for proteins, and a fundamental question in genomics is: What proportion of the noncoding mammalian genome is functional? Most attempts to address this issue use sequence comparisons between highly diverged mammals such as human and mouse to identify conservation due to negative selection. But such comparisons will underestimate the true proportion of functional noncoding DNA if there is turnover, if patterns of negative selection change over time. Here we test whether the inferred level of negative selection differs between different pairwise species comparisons. Using a multiple alignment of more than a megabase of contiguous sequence from eight mammalian species, we find a strong negative relationship between inferred levels of negative selection and pairwise divergence using 21 pairwise comparisons. This result suggests that there is a high rate of turnover of functional noncoding elements in the mammalian genome, so measures of functional constraint based on human-mouse comparisons may seriously underestimate the true value. KW - turnover N1 - do some alignments. estimate two parameters of interest: proportion of sites under purifying selection and the turnover rate AU - Smith, NG AU - Brandström, M AU - Ellegren, H PY - 2004/11// UR - http://dx.doi.org/10.1016/j.ygeno.2004.07.012 ER -