Impact of non-LTR retrotransposons in the differentiation and evolution of anatomically modern humans

Abstract

BackgroundTransposable 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s13100-018-0133-4) contains supplementary material, which is available to authorized users.

Factors Regulating the Activity of LINE1 Retrotransposons

“…However, the genomic architecture of L1 elements in ancient humans (Homo sapiens sapiens) and related subspecies, ancient hominids, (Neanderthals and Denisovans) are poorly understood due to the difficulties of genomic mapping of repeat elements using short reads available from the sequencing of ancient DNA. Nevertheless, several studies carried out an analysis of the mobile elements, which showed the presence of introgression of the L1 insertion loci of ancient people in the DNA of modern people, the nature of which corresponds to the same for SNV [98,99].…”

“…Thus, the origin of L1Ta1d could have occurred in the common ancestor of ancient hominids and modern humans more than 800 thousand years ago [98]. An analysis of the insertion loci in genes in ancient people and modern humans showed that most of the repeat insertion loci specific to modern humans, including L1, originated in the genes that are highly expressed in the brain and are involved in neuronal maturation [99].…”

Involvement of non-LTR retrotransposons in mammal cancer incidence and ageing

“…The longest living bat species here considered are Myotis lucifugus and Myotis myotis (Figure 1). As seen above (Figure 3, Figure 5, Table 1), the non-LTR retrotransposons are the most present types of TEs in Rodents and the most extensively investigated by biomedical research given that they are the only active TEs in the human genome [11]. Since the TEs that may pose the highest health threat to organisms are the ones presently active, we compared the most recent accumulation of non-LTR retrotransposons between long-lived and cancer-resistant species (H. glaber) and short-lived species commonly affected by cancer (Figure 3, Figure 5) using the density of insertion (DI).…”

“…They can accumulate in genomes and account for most of the organism genome size, for example, the human genome is > 50% repetitive [3]. Many studies show that TEs are implicated in gene duplications, inversions, exon shuffling, gene expression regulation and may play an important role in the long-term evolution of organisms [4][5][6][7][8][9][10][11][12]. For example, the co-option of TE-related proteins gave rise to vertebrate acquired immune system and mammalian placenta [13][14][15][16][17][18][19].…”

Evolutionary insights in Amazonian turtles (Testudines, Podocnemididae): co-location of 5S rDNA and U2 snRNA and wide distribution of Tc1/Mariner

“…Studies suggest that sites rich in repetitive sequences can be critical points for double-strand breaks, non-homologous recombination, and chromosomal reorganization in several organisms (Cazaux et al, 2011;Barros et al 2017;Cavalcante et al, 2018). Moreover, the high mobility of certain sequences (as transposable elements, or TEs) can enable them to interrupt the coding sequences of endogenous genes and modify their expression (Kemp and Longworth, 2015;Yin et al, 2018), or be co-opted for the regulation of host genes and thereby interfere with genome function and evolution (McCullers and Steiniger, 2017;Guichard et al, 2018).…”