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09:31
Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Integration target site selection by a resurrected human endogenous retrovirus
Troy Brady1, Young Nam Lee, Keshet Ronen
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Genes & Development
|March 10, 2009
Summary
Human endogenous retroviruses (HERVs) accumulate in the genome through a two-step process. Initial integration targets gene-rich areas, followed by selection against disruptive elements.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Human endogenous retroviruses (HERVs) constitute a significant portion of the human genome, originating from retroviral DNA integrations.
- Understanding the evolutionary forces shaping HERV distribution is crucial for deciphering their impact on genome evolution.
Purpose of the Study:
- To investigate the forces directing the accumulation of HERVs in the human genome.
- To compare de novo HERV integration targeting with the distribution of fixed HERV elements.
Main Methods:
- Utilized a reconstituted consensus HERV-K (HERV-K(Con)) to study de novo integration targeting.
- Analyzed the distribution of fixed HERV-K proviruses in the human genome.
- Compared integration site preferences, location within transcription units, and transcriptional orientation.
Main Results:
- De novo HERV-K(Con) integration preferentially occurred within transcription units and gene-rich regions.
- Fixed HERV-K proviruses are predominantly located outside transcription units.
- HERVs within transcription units show orientation bias to minimize host gene disruption, unlike de novo integrations.
- Youngest HERV-K elements exhibit an intermediate distribution, suggesting a transition phase.
Conclusions:
- HERV accumulation in the human germline is a two-step process involving initial integration targeting and subsequent purifying selection.
- Integration targeting biases initial HERV accumulation in specific genomic locations.
- Purifying selection acts to remove HERVs that disrupt essential gene functions, influencing their long-term distribution.
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