Fluorescence hybridization image of human chromosomes in metaphase. The probe glowing red is one that binds to telomeric DNA. The chromosome in the zoomed inset is human chromosome 2, which has telomeric DNA near its center, the point where two ancestral chromosomes fused together. Image from Ijdo and coworkers (1991).
Most living people have 23 pairs of chromosomes, as did our relatives known from ancient DNA, the Neandertals and Denisovans. All of our closest primate relatives—chimpanzees, bonobos, gorillas, and orangutans—have 24 pairs. From comparing these genomes with each other, it is clear that sometime during human evolution two ancestral chromosomes fused together, reducing our number. The product of that fusion is human chromosome 2, the second-largest of our chromosomes.
Evolutionary geneticists often focus closely on differences in chromosome numbers, which can be related to reproductive incompatibility between sister species. Structural changes to chromosomes may also affect gene regulation or other functions. Did the chromosome 2 fusion make a difference to our ancestors, maybe even cause an ancient speciation in our lineage?
Maybe the biggest barrier to understanding how this chromosome fusion mattered is a better knowledge of exactly when it happened. Recently geneticists led by Barbara Poszewiecka applied a creative approach to estimate how long ago the two ancestral chromosomes fused together. They found a surprisingly recent range of times: between 400,000 and 1.5 million years ago.
A new paper just published suggests that a major bottleneck in our evolutionary history happened between 930,000 and 800,000 years ago, and points to the chromosome 2 fusion as one possible consequence. This interval is a very interesting time. Our African ancestors, Neandertal ancestors, and Denisovan ancestors all diverged from each other around 700,000 years ago—and all these branches share the fused chromosome. It seems likely that the population that gave rise to these later hominins was the one in which the chromosome 2 fusion first evolved. That may have made a big difference to their interaction with other hominins that lived at the same time.
Characterizing the fusion
Geneticists demonstrated the correspondences of human and great ape chromosomes more than 40 years ago, visualizing their chromatin content by using special chemical stains. The resulting pattern of bands, still used in genetic maps, makes it very clear which chromosomes are homologous among these species and how they have changed. Aside from our fused chromosome 2, in other ways the human arrangement of chromosomes is actually conservative. For example, the common ancestors of chimpanzees and bonobos underwent pericentric inversions on seven different chromosomes, compared with only two for our ancestral lineage.
Genetic map ideogram of human chromosome 2 compared to the homologous chromosomes of other great apes. Map redrawn from Yunis and Prakash 1982.
Two great ape chromosomes correspond to the two halves of our chromosome 2, and geneticists often designate these as 2a and 2b. The chimpanzee and bonobo chromosomes are a closer match to ours than gorillas, because the human-chimpanzee ancestral population had a pericentric inversion of this ancestral chromosome, reversing the area immediately around its centromere.
When the ancestral chromosomes fused together, the shorter arm of ancestral 2a became connected to the shorter end of ancestral 2b. For some time the newly-fused chromosome had two centromeres. This is an unstable situation. Today the 2a centromere continues to function, while ancestral 2b centromere is just a tiny shadow of its former self. In a 2017 study, Georgia Chiatante and coworkers investigated how this happened. Centromeres differ in sequence and composition, but what they share is a large number of DNA repeats known as α (alpha) satellites, organized into arrangements that form higher-order repeat (HOR) units that are repeated hundreds or thousands of times. These sequence features interact with specialized histones and epigenetic processes to assemble the kinetochore protein complex that enables DNA replication. In human ancestors, a major deletion had eliminated most of the α satellite content of 2b, including most HOR structure.
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