Abstract

Gene and genome editing improves the prognosis by preventing non-target or pleiotropic consequences. Genomic editing targets can be assessed by localizing their structural and functional traits on the most polymorphic genomic elements, e.g., by transposons. This research clarified the distribution of transposons in the most popular gene editing targets and on their flanks in different mammalian species.
The study covered the genomic sequences of humans (Homo sapiens), cattle (Bos taurus), domestic rabbits (Oryctolagus cuniculus), and house mice (Mus musculus). It involved the protein-coding genes of myostatin (mstn), melanophilin (mlph), leptin receptor (lepr), X-localized chromatin remodeling protein (atrx), and three genes in the evolutionarily conserved chromatin loop (transcrip-tion regulation factor – auts2, N-acetylgalactosaminyl transferase – galnt17, calcium binding protein 1 – caln1), as well as at least four genes on their flanks. The distribution of transposons was estimated using RepeatMasker; the statistical processing relied on the Jamovi software. The analysis was conducted for the following gene and genomic traits: 1) the frequency of dispersed repeats that were dominant in ancestral species to be displaced by later varieties; 2) the correlation between the frequency and the localization in autosomes and chromosome X, the functional affiliation of gene groups, their localization in the same and different chromosomes, and gene overlap.
The differences in the frequencies of ancient and young transposons between humans, cattle, and rodents were associated with different rates of generational exchange. The research also revealed some links between the protein functions and the conservatism of genetic linkage. The blocks of genetically linked genes across the species differed in ancient transposons, which depended on the species-specific differences in the protection of the corresponding genomic regions from transpositions.
The data on species- and gene-specific traits of transposons distribution may help to prevent undesirable pleiotropic effects of genetic modifications.

Keywords

Gene editing, genetic linkage, chromatin loop, evolutionary conservatism, ancient and young transposons, Homo sapiens, Bos taurus, Oryctolagus cuniculus, Mus musculus

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