Kondrashov A S
Section of Ecology and Systematics, Cornell University, Ithaca, NY 14853, USA.
J Theor Biol. 1995 Aug 21;175(4):583-94. doi: 10.1006/jtbi.1995.0167.
It is well known that when s, the selection coefficient against a deleterious mutation, is below approximately 1/4Ne, where Ne is the effective population size, the expected frequency of this mutation is approximately 0.5, if forward and backward mutation rates are similar. Thus, if the genome size, G, in nucleotides substantially exceeds the Ne of the whole species, there is a dangerous range of selection coefficients, 1/G < s < 1/4Ne. Mutations with s within this range are neutral enough to accumulate almost freely, but are still deleterious enough to make an impact at the level of the whole genome. In many vertebrates Ne approximately 10(4), while G approximately 10(9), so that the dangerous range includes more than four orders of magnitude. If substitutions at 10% of all nucleotide sites have selection coefficients within this range with the mean 10(-6), an average individual carries approximately 100 lethal equivalents. Some data suggest that a substantial fraction of nucleotides typical to a species may, indeed, be suboptimal. When selection acts on different mutations independently, this implies too high a mutation load. This paradox cannot be resolved by invoking beneficial mutations or environmental fluctuations. Several possible resolutions are considered, including soft selection and synergistic epistasis among very slightly deleterious mutations.
众所周知，当针对有害突变的选择系数s低于约1/4Ne（其中Ne是有效种群大小）时，如果正向和反向突变率相似，该突变的预期频率约为0.5。因此，如果以核苷酸计的基因组大小G大大超过整个物种的Ne，就存在一个危险的选择系数范围，即1/G < s < 1/4Ne。s在此范围内的突变足够中性，可以几乎自由地积累，但仍然有害到足以在整个基因组水平上产生影响。在许多脊椎动物中，Ne约为10^4，而G约为10^9，因此危险范围包括四个以上数量级。如果所有核苷酸位点的10%发生的替换其选择系数在此范围内，平均值为10^-6，那么一个平均个体携带约100个致死当量。一些数据表明，一个物种特有的相当一部分核苷酸可能确实并非最优。当选择独立作用于不同突变时，这意味着突变负荷过高。这个悖论无法通过引入有益突变或环境波动来解决。文中考虑了几种可能的解决方案，包括软选择和非常轻微有害突变之间的协同上位性。
