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mFISH Mapped 16 of 22 Rhesus Macaque Chromosome Types to a Single Human Chromosome

Male rhesus macaque in Gokarna, Nepal

Multicolor fluorescence in situ hybridization (mFISH) mapped large-scale chromosome homology between humans and rhesus macaques (Macaca mulatta) and showed that most rhesus chromosome types correspond closely to a single human chromosome. The study used metaphase chromosomes from blood samples of three untreated adult male macaques and analysed about 3,000 cells.

mFISH is a molecular cytogenetic form of chromosome painting. Mixtures of fluorescently labelled DNA probes specific to each human chromosome are allowed to hybridize to matching DNA on macaque chromosomes. The resulting colour pattern identifies homologous chromosome material by DNA sequence content rather than relying only on chromosome shape or G-banding — characteristic staining patterns traditionally used to distinguish chromosomes.

Sixteen of 22 chromosome types had one-to-one homology

Rhesus macaques have 42 chromosomes — 20 pairs of autosomes plus X and Y. When each homologous pair is counted as one chromosome type, the karyotype, or complete chromosome set, contains 22 types. Sixteen of these each matched a single human chromosome, and thirteen had a human homologue carrying the same chromosome number. The result illustrates how much of the overall primate chromosome arrangement has remained conserved.

Three rhesus chromosomes preserved ancestral combinations

Three rhesus chromosome types had more complex one-to-two relationships. Rhesus chromosome 2 (MMU 2) contained material homologous to human chromosomes 7 and 21; MMU 7 corresponded to human chromosomes 14 and 15; and MMU 13 corresponded to human chromosomes 20 and 22. These patterns preserve chromosome combinations that were later separated in the human lineage. The ancestral 14/15 association, for example, is retained as MMU 7, whereas a fission around 25 million years ago produced separate human chromosomes 14 and 15 and was accompanied by new centromere positions, or neocentromeres.

Human chromosome 2 showed the opposite pattern

A single probe for human chromosome 2 labelled two pairs of acrocentric rhesus chromosomes — chromosomes whose centromere lies close to one end. MMU 9 matched the long arm of human chromosome 2 and MMU 15 the short arm. This split correspondence reflects the well-known evolutionary fusion that created human chromosome 2 from two ancestral primate chromosomes.

The molecular map also resolved disagreements left by older comparisons based largely on chromosome shape and G-banding. Several rhesus chromosomes had historically been assigned to the wrong human homologues because visually similar banding patterns did not always reflect DNA content accurately. The authors describe their work as the first complete rhesus macaque karyotype produced with the 24XCyte human mFISH probe set.

mFISH does not provide a gene-by-gene genome comparison; its strength is in revealing chromosome-scale homology and rearrangement. In that role, the study shows both sides of primate chromosome evolution: extensive conservation alongside a smaller number of fissions, fusions and other rearrangements that distinguish the human and rhesus karyotypes.

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