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Sergey G. Kurdyukov a , Yuri B. Lebedev a , Irena I. Artamonova a , Tatyana N. Gorodentseva a ,

GENE 273 (2001) 51-61 Full-sized HERV-K (HML-2) human endogenous retroviral LTR sequences on human chromosome 21: map locations and evolutionary history. Sergey G. Kurdyukov a , Yuri B. Lebedev a , Irena I. Artamonova a , Tatyana N. Gorodentseva a ,

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Sergey G. Kurdyukov a , Yuri B. Lebedev a , Irena I. Artamonova a , Tatyana N. Gorodentseva a ,

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  1. GENE 273 (2001) 51-61 Full-sized HERV-K (HML-2) human endogenous retroviral LTR sequences on human chromosome 21: map locations and evolutionary history Sergey G. Kurdyukova, Yuri B. Lebedeva, Irena I. Artamonovaa, Tatyana N. Gorodentsevaa, Anastasia V. Batraka, Ilgar Z. Mamedova, Tatyana L. Azhikinaa, Svetlana P. Legchilinab, Irina G. Efimenkob, Katheleen Gardinerc and Eugene D. Sverdlova, b a Shemyakin-Ovchinnikov Inst. of Bioorganic Chemistry, Russian Academy of Science, 16/10 Miklukho-Maklaya, Moscow, 117871, Russia. b Institute of Molecular Genetics, Russian Academy of Science, Moscow, Russiac Eleanor Roosevelt Institute, Denver, CO, USA 발표일시 : 2002년 1월 14일 발 표 자 : 김 명 숙

  2. ABSTRACT One of the evolutionary mechanisms for acquisition of novel functional sequences can be domestication of exogenous retroviruses that have been integrated into the germ line. The whole genome mapping of such elements in various species could reveal differences in positions of the retroviral integration and suggest possible roles of these differences in speciation. Here, we describe the number, locations and sequence features of the human endogenous retrovirus HERV-K (HML-2) long terminal repeat (LTR) sequences on human chromosome 21. We show that their distribution along the chromosome is not only non-random but also roughly correlated with the gene density. Amplification of orthologous LTR sites from a number of primate genomes produced patterns of presence and absence for each LTR sequence and allowed determination of the phylogenetic ages and evolutionary order of appearance of individual LTRs. The identity level and phylogenetic age of the LTRs did not correlate with their map locations. Thus, despite the non-random distribution of LTRs, they have apparently been inserted randomly into the chromosome relative to each other. As evidenced in previous studies of chromosomes 19 and 22, this is a characteristic of HERV-K integration.

  3. +LTR element Retrovirus

  4. 1. INTRODUCTION • Transposons have played an important role in the evolution. • LTRs make important features of the genome. • HERV-K LTR sequences contain •  putative hormone response elements, • enhancers, promoters, polyadenylation signals • and transcription factor binding sites. • To understand the role of the LTRs in the primate evolution •  to perform a whole genome comparison of the LTR • positions in various primates.

  5. Three criteria to choose these LTRs • (i) the LTRs should be full-sized • to comprise all regulatory elements • (ii) they should belong to a most • biologically active HERV-K • (iii) they should be located outside • of the clusters of interspersed repeats

  6. OBJECT • Sequenced human chromosome 21 • Mapping of some LTRs • Performed phylogenetic analysis • Determined the time of their appearance in the primate genomes • Identified human-specific LTRs

  7. 2. MATERIALS AND METHODS Table 1. Primers for genomic PCR 2.1. Oligonucleotide primers 2.2. Cosmid and YAC libraries screening 2.3. Amplification of LTR sequences 2.4. Cosmid analysis  Fluorescent in situ hybridization (FISH) 2.5. Isolation of LTR-flanking regions 2.6. Sequence analysis  Blast N  RepeatMasker 2  ClustalW  PHYLIP  Tree View 1.6

  8. 3. RESULTS 3.1. Isolation and mapping of LTR sequences 3.2. Distribution of the LTRs along Chr21 3.3. LTR sequence diversity 3.4. Non-random LTR distribution along chromosome versus random alternation of various LTRs 3.5. Individual LTR evolutionary ages and maintenance in primates

  9. Fig. 1. A HERV-K LTR nearest neighbor dendrogram (A) and an ideogram of human chromosome 21 (B) with LTR locations and (C) genes density.

  10. Table 2. Human genes in the vicinity of the LTRs

  11. Table 3. Phylogenetic assessment of the integration times for individual HERV-K LTRs in the primate genomes

  12. Fig. 2. The results of three individual LTR-containing loci PCR amplifications in the human and other primate genomes.

  13. 4. DISCUSSION 4.1. The distribution of the HERV-K LTRs along chr21 is roughly correlates with the gene distribution 4.2. LTR-gene relations 4.3. The intra- and interchromosomal distribution of the LTRs 4.4. LTRs of different ages are present on chr21, but relatively young LTRs are more abundant

  14. Fig. 3. Integration times of individual HERV-K elements mapped on Chr21.

  15. Fig. 6. Phylogenetic tree for the putative integration times of endogenous retrovirus/retroposon in primates branching times of the phylogeny should be considered as approximate.

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