ABSTRACT
BACKGROUND:
Transposable elements are biologically important components of
eukaryote genomes. In particular, non-LTR
retrotransposons (N-LTRrs) played a key
role in shaping the
human genome throughout evolution. In this study, we compared
retrotransposon insertions differentially present in the
genomes of Anatomically Modern
Humans,
Neanderthals, Denisovans and
Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the
human lineage.
RESULTS:
We first identified species-specific N-LTRrs and established their distribution in present day
human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern
Humans. These insertions are associated with an increase in the number of transcriptional/splicing variants of those
genes they inserted in. The
analysis of the functionality of
genes containing
human-specific N-LTRr insertions reflects changes that occurred during
human evolution. In particular, the expression of
genes containing the most recent N-LTRr insertions is enriched in the
brain, especially in undifferentiated
neurons, and these
genes associate in networks related to
neuron maturation and migration. Additionally, we identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern
humans, whose genomic loci show traces of positive selection.
CONCLUSIONS:
Our results strongly suggest that N-LTRr impacted our differentiation as a species, most likely inducing an increase in neural complexity, and have been a constant source of genomic variability all throughout the evolution of the
human lineage.
