Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

Abstract

Transposable elements (TEs) are recognized as major players in genome plasticity and evolution. The high abundance of TEs in the human genome, especially the Alu and Long Interspersed Nuclear Element-1 (LINE-1) repeats, makes them responsible for the molecular origin of several diseases. This involves several molecular mechanisms that are presented in this review: insertional mutation, DNA recombination and chromosomal rearrangements, modification of gene expression, as well as alteration of epigenetic regulations. This literature review also presents some of the more recent and/or more classical examples of human diseases in which TEs are involved. Whether through insertion of LINE-1 or Alu elements that cause chromosomal rearrangements, or through epigenetic modifications, TEs are widely implicated in the origin of human cancers. Many other human diseases can have a molecular origin in TE-mediated chromosomal recombination or alteration of gene structure and/or expression. These diseases are very diverse and include hemoglobinopathies, metabolic and neurological diseases, and common diseases. Moreover, TEs can also have an impact on aging. Finally, the exposure of individuals to stresses and environmental contaminants seems to have a non-negligible impact on the epigenetic derepression and mobility of TEs, which can lead to the development of diseases. Thus, improving our knowledge of TEs may lead to new potential diagnostic markers of diseases.

Human leukocyte antigen super-locus: nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes

“…Transposable elements (TEs) have important, albeit, often poorly defined roles in generating haplotypes via recombination mechanisms such as integration (insertion), duplication, rearrangements, deletions and gene conversion 64 , 65 . TEs and other repeat sequences appear to have been integral in the generation of MHC segmental duplications of the class I and class II regions 6 , 66 , and of different haplotypes, mainly by acting both as recombination acceptor and suppression sequence regions for DNA binding Rec proteins and enzymes such as PRDM9 depending on their genomic distribution, sequence conservation or diversity, and evolutionary age of integration and transposition 13 , 14 .…”

Genome‐wide identification, phylogeny, and gene duplication of the epigenetic regulators in Fagaceae

“…An alternative hypothesis is that some Fagaceae proteins might have suffered deletion events which could be related with the presence of high number of TEs that are present in gene rich regions of the Fagaceae genomes (Alves et al, 2012 ; Mishra et al, 2022 ; Rocheta et al, 2012 ). In the human genome, the high abundance of LINE‐1 and Alu repeats favors recombination between non‐homologous loci leading to significant chromosomal rearrangements such as gene duplications and deletions (Chénais, 2022 ). Non‐LTR and LTR elements are represented in our data (Table S8 ), which is in overall accordance with what is described for their genomic representativity in these species (Mishra et al, 2022 ; Ramos et al, 2018 ; Shirasawa et al, 2021 ; Wang et al, 2020 ).…”

Nucleosomes and flipons exchange energy to alter chromatin conformation, the readout of genomic information, and cell fate

“…Over 20% of nucleotides are derived from long interspersed elements (LINEs), 13.2% from short interspersed elements (SINEs, of which 10.6% are from the Alu repeat family), 8.3% from long terminal repeat (LTR) retrotransposons, 2.8% from DNA transposons, and 6.8 % from simple sequences built with 1-6 nucleotides repeats (SSR). [103,104] SSR are the most mutagenic of these elements, with 8 983 547 loci reported, 4 551 080 of which are perfect repeats. [104] Just through the process of slippage during replication, SSR made from tetranucleotide repeats have a mutation rate of 10.01 × 10 −4 per locus per generation while the rate for dinucleotide SSR is 2.73 × 10 −4 per locus per generation.…”