Evolutionary dynamics of mammalian mRNA untranslated regions by comparative analysis of orthologous human, artiodactyl and rodent gene pairs

Evolutionary dynamics of mammalian mRNA untranslated regions by comparative analysis of orthologous human, artiodactyl and rodent gene pairs
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DOI:
10.1016/s0097-8485(02)00009-8
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发表时间:
2002-07-01
期刊:
COMPUTERS & CHEMISTRY
影响因子:
--
通讯作者:
Saccone, C
Saccone, C
中科院分区:
其他
文献类型:
--
作者:
Larizza, A;Makalowski, W;Saccone, C

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大多数基于分子数据的进化研究涉及编码蛋白质的基因组部分。然而,今天,人们越来越关注所谓的“非编码”区域,它构成了后生动物核基因组的重要部分。其中信使rna的非翻译区(mRNA UTRs)尤为重要,它参与调控基因表达,控制翻译效率以及mRNA的定位和稳定性。到目前为止,很少有研究集中分析utr的组成和结构特征,或对其进化动态进行定量研究。为此,我们对灵长类(智人)、偶蹄目(兽类)和啮齿类(鼠目)共93个同源基因三联体(通过系统发育方法选择,共645 625 nt)的5′和3′utr对应编码区的进化率进行了序间研究。我们的研究只考虑了可能的同源基因,揭示了这些区域在核苷酸取代率、索引和重复元件分布方面的有趣进化特征。来自不同基因的utr在进化动力学上表现出显著的异质性,一些同源基因的高度分化使其无法排列,而另一些则相当保守,至少在某些区域是如此;大多数发散序列对被排除在我们的分析之外。通过比较5‘和3’核苷酸替代率与同义编码位置的核苷酸替代率,我们可以验证和测量作用于不同基因的核苷酸替代率的功能约束的存在,这表明,在许多情况下,正选择驱动进化动力学。(C) 2002 Elsevier Science Ltd.版权所有。
Most evolutionary studies based on molecular data refer to the portion of genomes encoding for proteins. Today, however, more and more attention is paid to the so-called 'non-coding' regions, which constitute a notable portion of the metazoan nuclear genome. Among them, the untranslated regions of messenger RNAs (mRNA UTRs) are particularly important, as they are involved in the regulation of gene expression, controlling translation efficiency as well as mRNA localization and stability. Up to now, only few studies have focused on the analysis of the compositional and structural features of UTRs, or carried out to investigate quantitatively their evolutionary dynamics. For this reason we have carried out an inter-order study on the evolutionary rate of 5' and 3' UTRs with respect to the corresponding coding region in 93 triplets of orthologous genes (selected through a phylogenetic approach, for a total of 645 625 nt) belonging to Primates (Homo sapiens), Artiodactyla (Bos taunts) and Rodentia (Mus spp.). Our study, that considered only likely orthologous genes, has revealed interesting features on the evolution of these regions concerning nucleotide substitution rate and indels and repetitive element distribution. UTRs from different genes showed a remarkable heterogeneity in the evolutionary dynamics, with some homologous so highly divergent to prevent their alignment, and other rather conserved, at least in some regions; most divergent sequence pairs were excluded from our analysis. The comparison between the nucleotide substitution rates calculated for 5' and 3' UTRs with those calculated on synonymous coding position allowed us to verify and measure the existence of functional constraints acting upon the UTRs of different genes which have shown, in many cases, a positive selection driven evolutionary dynamics. (C) 2002 Elsevier Science Ltd. All rights reserved.