Problems in Evolutionary Theory

对生存或生育有有害影响的等位基因的基因突变发生在所有生物体的种群中，任何生物体基因组中所有位点的净突变率现在被认为是非常高的。严重有害的突变是人类群体中许多疾病的原因，而影响较小的突变可能是人类疾病中最重要的，尽管人们对这些突变知之甚少，因为它们很难研究。在初步研究中，研究人员发现，在基因组的一个区域发生有害突变会影响同一区域DNA序列的进化。他们发现，在不影响适应度的核苷酸位点上的遗传变异在这样一个区域会大大减少。研究人员将量化这种影响与基因图谱上基因之间距离的关系，并将研究扩展到确实有轻微适应性影响的序列差异。在解释这些数据时，重要的是要包括一些生物学上重要的现象，如基因图谱中邻近位点的有害突变。这在以前的理论研究中还没有做过。结果将对解释种群内变异性和种群间进化差异的数据产生影响。DNA序列的这种差异已被用作确定物种起源时间的“分子钟”，也被用来推断自然选择导致了观察到的差异。当遗传背景中的其他基因座被纳入模型时，除了正在研究的基因座之外，自然选择的推断可能变得不那么确定，并且分子钟的速率可能被证明受到基因在遗传图谱中的位置和近交种群水平的影响。

9317683 Charlesworth Mutation of genes to alleles with deleterious effects on survival or fertility occurs in the populations of all living organisms, and the net rate of mutation summed up over all the loci in the genome of any organism is now thought to be very high. Severely deleterious mutations are the cause of many diseases in human populations, and mutations with lesser effects are probably most important in human disease, though little is known about these as they are difficult to study. In a preliminary study, the investigators found that the occurrence of deleterious mutations in a region of the genome affects the evolution of DNA sequences in the same region. They have found that genetic variability at nucleotide sites that themselves do not affect fitness can be greatly reduced in such a region. The investigators will quantify this effect in relation to distances between the genes on the genetic map, and will extend studies to sequence differences that do have slight fitness effects. It is important in interpreting such data to include such biologically important phenomena as deleterious mutations of loci nearby in the genetic map to those under study. This has not previously been done in theoretical studies. %%% Results will have implications for the interpretation of data on variability within populations and on evolutionary divergence between populations. Such divergence in DNA sequences has b een used as a "molecular clock" to date the times of origin of species, and has also been used to infer that natural selection caused the observed differences. When other loci in the genetic background are included in the models, in addition to the loci under study, the inference of natural selection may become less certain, and that the rate of the molecular clock may prove to be influenced by the locations of genes in the genetic map, and by the level of inbreeding populations.