Biology Reference
In-Depth Information
distant evolutionary past, however. Active mobile lineages continue to propa-
gate within the majority of eukaryotic species surveyed thus far, including
humans. Whereas the activity of these elements was once believed to be focused
exclusively within the germline, there is now emerging evidence for substantial
TE activity within somatic tissues. Much remains to be understood concerning
the impact of this ongoing somatic activity on organismal fitness and, ultimately,
upon human health. Here, we examine recent progress in human TE research,
focusing on advances in our understanding of the relationship between element
and host. Concentrating on the human genome and its current set of TE
inhabitants, we examine both the positive and negative consequences of histori-
cal and ongoing TE activity.
A. Mobilization and classification
TE mobilization mechanisms can be divided into two broad categories, based on
whether an RNA or DNA intermediate is used during the transposition process.
These two varieties of mobilization have been conveniently described as “copy and
paste” and “cut and paste,” and they form the basis of a common categorization
scheme of TEs introduced by Finnegan (1989), which divides TEs into Class I and
Class 2 elements. According to the original criteria, Class 2 elements are those
that mobilize directly from DNA to DNA, without the use of an RNA intermedi-
ate (Van Duyne, 2002). With some exceptions, noted below, DNA transposition
occurs through a “cut and paste,” strategy, where the original double-stranded
DNA source element is excised from its existing location and reintroduced to a
novel location in the genome. This excision is accomplished by transposase
proteins that are encoded directly by the transposons themselves, or, in some
cases, hijacked from other transposons in the host genome that possess protein-
coding capacity. These same transposase proteins also facilitate the reintegration
of the excised element elsewhere in the genome. With some important exceptions
that allow for copy number increase, this type of mobilization is conservative in
nature, resulting in no overall increase in the total number of TE elements within a
host genome. It was representatives of the Class 2 type of elements that McClin-
tock first observed in maize (McCLINTOCK, 1950). Discoveries of additional
DNA transposons varieties that, despite their use of a DNA intermediate, did not
include a double-stranded DNA removal step during the transposition process,
necessitated the updating of Class 2 DNA transposon class to include three
distinct subcategories. These include the original “cut and paste transposons,”
Helitrons, and Mavericks (reviewed in Feschotte and Pritham, 2007). The second
major class of TEs, termed Class 1 elements (also commonly referred to as retro-
transposons), mobilize by generating RNA transcripts that are subsequently con-
verted into DNA prior to reintegration at a novel location in the host genome.
Again, the process is mediated by proteins that are either encoded directly by the
