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Background  In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes.    Results  Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years ago.    Hypotheses  I propose that, unlike recurrent Robertsonian translocations in humans, the HSA2 fusion was a single nonrecurrent event that spread through a small polygamous clan population bottleneck. Its heterozygous to homozygous conversion, fixation, and accumulation in the succeeding populations was likely facilitated by an evolutionary advantage through the genomic loss rather than deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.    Conclusions  The origin of HSA2 might have been a critical evolutionary event influencing higher cognitive functions in various early subspecies of hominins. Next generation sequencing of  Homo heidelbergensis  and  Homo erectus  genomes and complete reconstruction of DNA sequence of the orthologous subtelomeric chromosomes in Great Apes should enable more precise timing of HSA2 formation and better understanding of its evolutionary consequences.

One pedigree we all may have come from – did Adam and Eve have the chromosome 2 fusion?