Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
Mol Biol Evol. 2012 Jan;29(1):179-86. doi: 10.1093/molbev/msr192. Epub 2011 Jul 29.
Intron density is highly variable across eukaryotic species. It seems that different lineages have experienced considerably different levels of intron gain and loss events, but the reasons for this are not well known. A large number of mechanisms for intron loss and gain have been suggested, and most of them have at least some level of indirect support. We therefore figured out that the variability in intron density can be a reflection of the fact that different mechanisms are active in different lineages. Quite a number of these putative mechanisms, both for intron loss and for intron gain, postulate that the enzyme reverse transcriptase (RT) has a key role in the process. In this paper, we lay out three predictions whose approval or falsification gives indication for the involvement of RT in intron gain and loss processes. Testing these predictions requires data on the intron gain and loss rates of individual genes along different branches of the eukaryotic phylogenetic tree. So far, such rates could not be computed, and hence, these predictions could not be rigorously evaluated. Here, we use a maximum likelihood algorithm that we have devised in the past, Evolutionary Reconstruction by Expectation Maximization, which allows the estimation of such rates. Using this algorithm, we computed the intron loss and gain rates of more than 300 genes in each branch of the phylogenetic tree of 19 eukaryotic species. Based on that we found only little support for RT activity in intron gain. In contrast, we suggest that RT-mediated intron loss is a mechanism that is very efficient in removing introns, and thus, its levels of activity may be a major determinant of intron number. Moreover, we found that intron gain and loss rates are negatively correlated in intron-poor species but are positively correlated for intron-rich species. One explanation to this is that intron gain and loss mechanisms in intron-rich species (like metazoans) share a common mechanistic component, albeit not a RT.
真核生物的内含子密度差异很大。似乎不同的谱系经历了相当不同水平的内含子获得和丢失事件，但原因尚不清楚。已经提出了大量的内含子丢失和获得的机制，其中大多数都至少有一定程度的间接支持。因此，我们认为内含子密度的可变性可以反映出不同的机制在不同的谱系中活跃的事实。相当多的这些假定的机制，无论是对于内含子的丢失还是获得，都假设逆转录酶（RT）在这个过程中起着关键作用。在本文中，我们提出了三个预测，这些预测的验证或证伪表明 RT 参与了内含子的获得和丢失过程。测试这些预测需要有关个体基因在真核生物系统发育树的不同分支上的内含子获得和丢失率的数据。到目前为止，还无法计算这些速率，因此，这些预测无法得到严格评估。在这里，我们使用了我们过去设计的一种最大似然算法，即期望最大化的进化重建，该算法允许估计这些速率。使用该算法，我们计算了在 19 种真核生物系统发育树的每个分支上超过 300 个基因的内含子丢失和获得率。基于此，我们发现 RT 活性在内含子获得中几乎没有得到支持。相比之下，我们认为 RT 介导的内含子丢失是一种非常有效的去除内含子的机制，因此其活性水平可能是内含子数量的主要决定因素。此外，我们发现，在内含子较少的物种中，内含子获得和丢失率呈负相关，而在内含子丰富的物种中则呈正相关。对此的一种解释是，内含子丰富的物种（如后生动物）中的内含子获得和丢失机制具有共同的机制成分，尽管不是 RT。
