Now, scientists led by the Wellcome Sanger Institute and University of Geneva believe they have uncovered the long-sought mechanism responsible for this enigma, involving large loops of DNA that interact with and lead to genetic exchanges involving chromosomal regions millions of letters long. The study, published in Science Advances, resolves much of the confusion concerning gene synteny conservation: the idea that the arrangement of gene clusters is relatively consistent between related species across evolutionary history.
As described in the report, these genomic inversions occur through a molecular machinery—known as non-allelic homologous recombination (NAHR)—where two segments of DNA, not necessarily on the same chromosome, that happen to share significant identity, interact and lead to breakage at the matching locations. Genetic material from these different chromosomal positions can swap or get reversed upon such recombination, thereby switching or changing the orientations of entire gene clusters within chromosomes.
"In mammals, we know that chromosomes come in male- and female-specific variants with different evolutionary histories. We observed a striking accumulation of NAHR events—more frequent compared to autosomes or even sex chromosomes in other vertebrates—on the male sex chromosomes of numerous organisms, from platypus to mouse, cattle, cat, macaque, gibbon, human and great ape species," explains Dr. Manuel Campos from the Wellcome Sanger Institute, leading author of the research.
NAHR can also occur between DNA segments originating from the same duplicated locus on the same chromosome arm; this could happen, for example, following gene duplication events. Gene clustering—especially on sex chromosomes—has also been proposed to aid gene regulation, for instance as gene neighbors often encode for proteins that form part of the same molecular pathways or biological process.
