Biology Reference
In-Depth Information
bottlenecks, have been suggested. Both the evidence of changing levels of TE
diversity, as well as for large fluctuation in insertion rates over evolutionary time,
demonstrate that the relationship between TE and host genome is not a static one.
Both host and TE are concurrently evolving and external perturbations from the
environmental can cause the landscape of insertion rates and element diversity to
shift, sometimes dramatically. Across taxa, this can be observed in the existence of a
diverse genomic ecologies of TEs and host [discussed in Brookfield, 2005]. These
range fromsystems containing a large diversity of elements, eachof whichhave but a
few genomic instances, to those systems, like the human, where a select few families
achieve very high copy numbers. While many important questions remain to be
answered regarding the impact of host demographic history on TE expression, it has
become clear that factoring heavily into the resulting TE ecology is the extent to
which host molecular biology augments or intervenes with TE proliferation. To
understand how the molecular biology of the host cell can help or hinder the
mobilization process, we will now examine in more detail the life cycle of the
human retrotransposon.
III. EXPRESSION AND REGULATION
In order to survive and impose lasting genetic alterations on future generations, TE-
associated modification of the host genome must ultimately occur in the germline—
at least within organisms that have a sequestered germline. From the selfish gene
perspective, activity in somatic cells would appear to only reduce genetic fitness of
the host without resulting in any increase in TE copy number. This relatively
simple—yet ultimately incomplete—evolutionary logic resulted in decades of
near-exclusive focus on the germline as the principal site of mammalian TE expres-
sion. While TE expression and proliferation within the germline remains the only
means of ensuring long-termTE survival, as we describe below, there is now emerging
evidence that somatic TE activity is considerably higher than once suspected.
A more complete characterization of this somatic activity is a vital component of
understanding the full impact of TEs on organismal fitness and, ultimately, human
health, and well being. On account of the ongoing tension in the TE-host coexis-
tence, a network of defense mechanisms has been erected by host cells to shield
the genome from unchecked TE activity. An understanding of the TE life cycle is
essential for appreciating the breadth and complexity of this regulatory network.
A. Life cycle of human retroelements
Among the human TEs that have retained their activity throughout the course of
evolution are three main groups of non-LTR retrotransposons (L1, Alu, and
SVA) that stand apart from the LTR group of retroelements such as HERVs.
