Introns Evolution in Duplicated Human Genes

Abstract

The material covered herein touches on the recent understanding of the fate of introns in human duplicated genes. A structural genomics framework has been provided to account for the functional asymmetry of sister copies after the duplication event(s). Structural shift between duplicated copies are very remarkable. Indeed, translocation/transposition of newly born copies to other chromosomal areas are accompanied not only by aminoacid substitutions but also by dramatic changes in introns size, composition and splicing patterns, as well as the emergence of intronic CpG‐island and other regulatory DNA elements. As an evolutionary working hypothesis, for the short‐term evolution (within mammalian orders), interchromosomal translocations may be followed by accelerated evolution (relaxed constraints) and consequently alteration in expression patterns of the displaced copy, with major changes in introns constitution. For the long term, namely at the compositional transition that characterises fish/amphibian and mammalian regional genome patterns (isochores), the translocated copies (gene copies of the gene‐dense ‘ancestral genome core’) underwent a strong guanine+cytosine (GC) enrichment to become the genes of the actual ‘genome core’ (actual open chromatin). Introns from these copies, in concert with their genomic surrounding, had accumulated major structural changes and their host genes acquired different functions and/or regulations. Key Concepts: Noncoding DNA; open chromatin; negative selection; recombination hot spots. Noncoding DNA: DNA sequences that do not encode for protein sequences and was therefore sometimes referred to as ‘junk DNA’, but for which there is now ample evidence for functionality (e.g. micro RNAs, ribozymes and long ncRNA). Open chromatin: It forms euchromatin, which contains regions harbouring promoters, enhancers and actively transcribed genes. Recombination hot spots: Regions of the chromosome that have frequent recombination events. Negative selection: Selection acting to eliminate emerging deleterious mutations that reduces carriers fitness. It is also called purifying selection.

The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis

“…This is also supported by gene replacement experiments in transgenic mice [ 11 ]. Antagonistic relations are unlikely, not only because of sequence divergence of the two proteins, but also because of a change in the chromatin context following duplication and translocation [ 43 , 44 ], leading to tissue specificity and limited competition between CTCF and CTCFL on DNA binding sites. Moreover, the physical CTCF-BORIS interaction in germ cells is an argument in favor of cooperative rather than antagonistic relations [ 11 ].…”