Transcript human endogenous retroviral LTR

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, Russia
c Eleanor Roosevelt Institute, Denver, CO, USA
발표일시 : 2002년 1월 14일
발 표 자 : 김 명 숙
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 nonrandom 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.
+LTR element
Retrovirus
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.
• 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
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
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
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
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.
Table 2. Human genes in the vicinity of the LTRs
Table 3. Phylogenetic assessment of the integration times for
individual HERV-K LTRs in the primate genomes
Fig. 2. The results of three individual LTR-containing loci PCR amplifications
in the human and other primate genomes.
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
Fig. 3. Integration times of individual HERV-K elements mapped on Chr21.
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.