Transcript Allelic Variation of HERV-K(HML

Allelic Variation of HERV-K(HML-2)
Endogenous Retroviral Elements
in Human Populations
138th lab seminar
신호수
2005.02.12
Introductions
HERV-K
1. putative tRNA primer binding sites for
Lysine
2. HERV-K10, phylogenetic analysis of RT
region : 6 HERV-K subgroups, HML-1 to
HML-6
3. HML-2 group was integrated
approximately 28 million years ago
4. HML-2 proviral genomes are classified 2
types
Introductions
In this study,
Examined the genomic structure and
integration sites of HML-2 elements that
are unique to humans and have
investigated their potential role in the
remodeling of human genome. and
analyzed their utility for the study of
human genomic diversity
Materials and Methods
1. Identification of HERV-K(HML-2)
polymorphism
2. DNA samples and PCR primers and
conditions – samples from chimpanzee and gorilla
along with 25 Africans, 28 Asians, 22 European, and 34
Papua New Guinean humans
3. Sequence and population genetic analysis
Results
1. Activity of HERV-K elements within the
human lineage
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3 novel sequences – 4p16,Xq28,10q24.2
Formerly identified complete and nearcomplete sequences
8 of 18 human specific HML-2
proviral genomes type Ⅰand 10
were type Ⅱ
Results
2. Inter- and Intra elements recombination –
comparison of direct repeat sequences
Results
3. Phylogeny of HML-2 LTRs unique to humans
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87 full length HML-2 LTR aligned – NJ tree
Individual LTR sequences are identified
according to their consensus name or genomic
location
HERV-K 115
LTR
divergence
Intraelement
recombination
Results
4. Relative age of HML-2 Loci
Discussion
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Copy number of HML-2 LTRs
Interlocus Recombination
Gene conversion of HML-2 proviral Loci
HERV-K(HML-2) polymorphisms for the
study of human evolution
Discussion
HERV-K(HML-2) polymorphisms for the
study of human evolution
Advantages for study human genomic diversity with HERV
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Largr numbers of DNA samples can be rapidly typed using PCR
De-novo insertionof a HERV suquence within the germ line represents a
unique event in human genome evolution
HERV sequences are stable
Ancestal state of a HERV squence is ultimately its absence and is
represented by preintegration site
LTRs can serve as a molecular clock
Discussion
These results further emphasize that for
recent evolutionary events,the accumulative nucleotide
differences of the LTRs of a HML-2 provirus do not serve
as an accurate measure of time since insertion. world.
Our survey of the human genomic diversity of HML-2 loci
Indicates that the genetic diversity of the African
population is far higher than non-African populations and
that 90.2 to 99.4% of this genetic variability is within a
population, supporting a recent demographic expansion
of modern humans from Africa.