Genomes of most vertebrates contain endogenous retroviruses as stably heritable elements. In human genome about eight percent are formed by endogenous retroviruses and their fragments.
The structure of endogenous retroviruses is the key to the interest in their evolution and functional role in the genome due to many regulator elements they include. These elements are a promoter, an enhancer, a polyadenilation site and others.
One of the most widespread and functionally conserved families of endogenous retroviruses, the HERV-K family, is represented in genome not only by retrovirus-like sequences but also by much more abundant long terminal repeats (LTR). A solitary LTR retains many regulator elements and consequently is able to modulate activity of adjacent genes. This study aimed at evolutionary analysis of HERV-K (HML-2) LTRs in the human genome.
The sequences under consideration are relatively abundant in the genome. We estimate the total amount of HERV-K LTR sequences as 1200 copies per haploid genome. We analyzed locations of HERV-K LTRs in the human genome and compiled a complete databank of these LTRs. Distribution of LTR sequences in individual chromosome was studied. It was proved to be highly non-uniform with respect to chromosome lengths. The density of LTRs varies significantly between chromosomes. All human chromosomes can be divided into two classes, those with relatively high or low LTR content. Analysis in LTR positions in individual chromosomes demonstrated that the majority of HERV-K LTR form clusters with the level of local LTR density more than 5 times higher than that for the whole chromosome. Almost every chromosome contains 1-5 LTR clusters. We described 68 clusters of LTR sequences. Clusters are formed by LTRs from different HERV-K subfamilies. However, there is no direct correlation between the proximity of LTRs in the cluster and their structural divergence. This is the ground for a hypothesis that successive infections were independent but human chromosomes contain regions preferable for retrotransposition.
In order to understand the features of the retrotransposition mechanism, we analyzed the genomic environment of the LTR localization sites and statistical and structural characteristics of the LTR cluster regions. There is no correlation between the positions of LTR clusters and the local density of SNPs and boundaries of the mouse-human synteny regions. On the other hand, positions of LTR clusters correlate with the Giemsa segmentation of human chromosomes. Moreover, LTRs tend to localize within GC-rich regions of the genome.
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Kurdyukov, S., Lebedev, Y., Artamonova, I., Gorodentseva, T., Batrak, A., Mamedov, I., Azhikina, T., Legchilina, S., Efimenko, I., Gardiner, K. and Sverdlov, E. (2001) Full-sized HERV-K (HML-2) human endogenous retroviral LTR sequences on human chromosome 21: map locations and evolutionary history. Gene 273, 51-61.
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