The Evolutionary History Of Human Chromosomes

This section recapitulates the evolutionary history of selected chromosomes, which are rearranged in human and great apes and for which molecular cytogenetic evidence is available. Figure 4 summarizes all hominoid evolutionary rearrangements.

Chromosome 2

The ancestral condition for all mammals is two separate chromosome 2 homologs. One is homologous to human 2pter-q13, the other to the remaining 2q13-qter segment. Comparative studies with a human chromosome 2q arm-specific paint probe, cosmid clones derived from the human V k gene cluster, and yeast artificial chromosomes (YACs) indicated that the chimpanzee and the macaque 2pter-q13 homologs may be ancestral, whereas in gorilla and orangutan, independent and probably convergent inversions involving the pericentromeric region of the 2p homolog may have occurred (45-47). More recently, a detailed FISH study with 2q12-14 cosmids revealed the same clone order in human and chimpanzee, which differed from that in the macaque (48).

Chromosome 3

According to one study, the putative ancestral primate chromosome 3 homolog is conserved in the Brown lemur, from which a pericentric inversion led to the ancestral Old World primate homolog conserved in the Bornean orangutan (49). Human/African ape homologs would differ from this chromosome form by two inversions. An even more complex scenario involving several recurrent sites of new centromere seeding was proposed by Ventura et al. (50), according to which human and Bornean orangutan would differ by three inversions. A third hypothesis suggested that from the ancestral simian homolog a common derived and two independent inversions would lead to Bornean orangutan and human chromosome 3 homologs (51). In conclusion, the evolutionary history of human chromosome 3 is probably the most dynamic and complex of all human chromosomes studied in detail so far.

Chromosome 4

Detailed comparative studies on the evolution of human chromosome 4 homologs of great apes and the macaque (52) indicated that the human homolog would represent the ancestral hominoid chromosome form. A minimum of seven different breakpoints were observed, some of them were located in the 4p pericentromeric region (52). For three of these inversions breakpoint spanning YAC clones were identified, of which one was confirmative for a previous analysis (53). Interestingly, one clone showed a split signal in chimpanzee and macaque, indicating two independent evolutionary breakpoints in close proximity to each other.

Chromosome 5

Both chromosome bar codes and detailed Zoo-FISH studies with YACs and subregional paint probes identified the chromosome forms shared by macaque, orangutan, and human to be ancestral for hominoids (54,55). From this, the homolog of the chimpanzee is directly derived by a pericentric inversion, those of the gorilla by a reciprocal translocation t(5;17) (1).

Chromosome 6

In a recent FISH study (56), it was shown that the remarkable conservation of chromosome 6 is also present at the subchromosomal level. Despite this, evolutionary centromere relocation events were observed. One of these events may have occurred in the ancestor of great apes, where the centromere moved from 6p22.1 to the present day location. This hypothesis gained support from the observation that in the assumed ancestral location in a cluster of intrachromosomal segmental duplications was found, which the authors explained as remnants of duplicons that flanked the ancestral inactivated centromere (56).

Chromosome 7

A FISH study on evolutionary changes of human chromosome 7 revealed that the ancestral mammalian homologs were comprised of two chromosomes (7a and 7b/16p) as observed in carnivores (57). The ancestral primate segment 7a shared by a lemur and higher Old World monkeys is the result of a paracentric inversion. The ancestral higher primate chromosome form was derived by a fission of 7b and 16p, followed by a centric fusion of 7a/7b in higher Old World primates as observed in the orangutan. In hominoids two further inversions with four distinct breakpoints occurred: the pericentric inversion in the human/African ape ancestor and the paracentric inversion in the common ancestor of human and chimpanzees (Fig. 5) (57).

Fig. 5. Hominoid chromosome 7 evolutionary rearrangements delineated by comparative sequence maps of human and rat (R) and cross-species fluorescence in situ hybridization with gibbon painting probes (G). Both data sets visualize the inversion breakpoints and their evolutionary direction by an increasingly simple pattern when tracking the rearrangements in the evolutionary reverse direction. Horizontal bars indicate inversion breakpoints.

Fig. 5. Hominoid chromosome 7 evolutionary rearrangements delineated by comparative sequence maps of human and rat (R) and cross-species fluorescence in situ hybridization with gibbon painting probes (G). Both data sets visualize the inversion breakpoints and their evolutionary direction by an increasingly simple pattern when tracking the rearrangements in the evolutionary reverse direction. Horizontal bars indicate inversion breakpoints.

Chromosome 9

Zoo-FISH with 12 evenly spaced YAC clones (58) revealed an identical marker order in Old and New World monkeys, which may therefore represent the ancestral chromosome form for higher primates. A paracentric inversion would derive the ancestral hominoid chromosome form, which was conserved in orangutan and gorilla. A further pericentric inversion would lead to the chromosome form of the last common ancestor of human and chimpanzee. Human conserved this evolutionary intermediate chromosome form, from which the homolog of chimpanzees differs by another pericentric inversion. One of the inversion breakpoints in the chimpanzee homolog was previously identified (53). As for the evolution of human chromosomes 3 and 6, this reconstruction takes into account the evolutionary emergence of neocentromeres.

Chromosome 10

The evolutionary history of human chromosome 10 was tracked by Zoo-FISH with a panel of partial chromosome paint probes, YACs, and BACs (59). These results suggest that in the inferred primate ancestor chromosome 10 homologs were organized as two separate syntenic units, whereas the observation of a single chromosome 10 homolog in two galago species (prosimians) (14) would argue for a single chromosome 10 in the ancestral primate. Additional data on other prosimian species may be required to clarify this issue. Among hominoid primates, the ancestral chromosome form is conserved by orangutan, from which the ancestor of human and African apes is derived by a paracentric inversion. A further species-specific pericentric inversion occurred in the gorilla homolog (55,59).

Y Chromosome

The mammalian Y chromosome shows a broad spectrum of species-specific rearrangements (60). To explain the morphology of the human Y chromosome in comparison to those of the great apes, at least a pericentric and a paracentric inversion specific for the human lineage have to be assumed. Another pericentric inversion was observed in the gorilla homolog. Further, a translocation from chromosome 1 to the Y chromosome took place in a common ancestor of humans and chimpanzees. In addition, submicroscopic deletions and duplications occurred in human, chimpanzee, and orangutan (60).

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