Plasticity of human chromosome 3 during primate evolution

doi:10.1016/j.ygeno.2003.08.012

Genomics

Volume 83, Issue 2, February 2004, Pages 193-202

https://doi.org/10.1016/j.ygeno.2003.08.012 Get rights and content

Abstract

Comparative mapping of more than 100 region-specific clones from human chromosome 3 in Bornean and Sumatran orangutans, siamang gibbon, and Old and New World monkeys allowed us to reconstruct ancestral simian and hominoid chromosomes. A single paracentric inversion derives chromosome 1 of the Old World monkey Presbytis cristata from the simian ancestor. In the New World monkey Callithrix geoffroyi and siamang, the ancestor diverged on multiple chromosomes, through utilizing different breakpoints. One shared and two independent inversions derive Bornean orangutan 2 and human 3, implying that neither Bornean orangutans nor humans have conserved the ancestral chromosome form. The inversions, fissions, and translocations in the five species analyzed involve at least 14 different evolutionary breakpoints along the entire length of human 3; however, particular regions appear to be more susceptible to chromosome reshuffling. The ancestral pericentromeric region has promoted both large-scale and micro-rearrangements. Small segments homologous to human 3q11.2 and 3q21.2 were repositioned intrachromosomally independent of the surrounding markers in the orangutan lineage. Breakage and rearrangement of the human 3p12.3 region were associated with extensive intragenomic duplications at multiple orangutan and gibbon subtelomeric sites. We propose that new chromosomes and genomes arise through large-scale rearrangements of evolutionarily conserved genomic building blocks and additional duplication, amplification, and/or repositioning of inherently unstable smaller DNA segments contained within them.

Section snippets

Syntenic relationships of HSA 3 and PPY 2

To track the evolutionary history of HSA 3 in primates, we selected more than 100 yeast artificial chromosomes (YACs) that are more or less evenly spaced on the human chromosome 3 (Supplementary Table 1). Hybridization of these YACs on Bornean and Sumatran orangutan chromosomes (Fig. 1, second column; Figs. 2A–2C) allowed us to delineate four DNA segments, which have been conserved in their entirety between human and Bornean orangutan (Fig. 3). For convenience's sake these segments were marked

Chromosome preparations

Metaphase chromosomes were obtained from peripheral blood lymphocytes, EBV-transformed lymphoblasts and fibroblasts of humans, Bornean and Sumatran orangutans and their hybrids, siamang gibbon, silvered-leaf monkey, and Geoffroy's marmoset following standard protocols. Briefly, 10 μg/ml colcemid (Roche) was added to the culture medium (RPMI 1640 or DMEM) supplemented with 10% fetal bovine serum, 2 mM glutamine, and antibiotics 25 min before cell harvest to arrest cells in metaphase. The cell

Acknowledgements

The authors thank Reinhard Göltenboth, Johannes Wienberg, Fengtang Yang, and Hans Zischler for primate blood samples and cell lines; Susanne Freier, Corinna Menzel, and Karen Stout for technical support; and Gail Craswell for critically reading the manuscript. This study was supported by the German Research Foundation (HA 1374/5-2) and the Boehringer Ingelheim Foundation.

References (47)

J. Rogers et al.
A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms
Genomics
(2000)
A. de Pontbriand et al.
Synteny comparisons between apes and human using fine-mapping of the genome
Genomics
(2002)
E. Nickerson et al.
Molecular definition of pericentric inversion breakpoints occurring during the evolution of humans and chimpanzees
Genomics
(1998)
H. Kehrer-Sawatzki et al.
Molecular characterization of the pericentric inversion that causes differences between chimpanzee chromosome 19 and human chromosome 17
Am. J. Hum. Genet.
(2002)
F.C. Chen et al.
Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees
Am. J. Hum. Genet.
(2001)
J.K. Sherlock et al.
Homologies between human and marmoset (Callithrix jacchus) chromosomes revealed by comparative chromosome painting
Genomics
(1996)
D.J. Amor et al.
Neocentromeres: role in human disease, evolution, and centromere study
Am. J. Hum. Genet.
(2002)
R.W. DeBry et al.
Human/mouse homology relationships
Genomics
(1996)
P. Stankiewicz et al.
Molecular-evolutionary mechanisms for genomic disorders
Curr. Opin. Genet. Dev.
(2002)
V. Brand-Arpon et al.
A genomic region encompassing a cluster of olfactory receptor genes and a myosin light chain kinase (MYLK) gene is duplicated on human chromosome regions 3q13–q21 and 3p13
Genomics
(1999)

G.R. Sutherland et al.

Fragile sites still breaking

Trends Genet.

(1998)

C. Brewer et al.

A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality — and tolerance of segmental aneuploidy — in humans

Am. J. Hum. Genet.

(1999)

H. Telenius et al.

Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer

Genomics

(1992)

S.J. O'Brien et al.

Ancestral primate viewed

Nature

(1999)

B.P. Chowdhary et al.

Emerging patterns of comparative genome organization in some mammalian species as revealed by Zoo-FISH

Genome Res.

(1998)

F. Yang et al.

Reciprocal chromosome painting among human, aardvark, and elephant (superorder Afrotheria) reveals the likely eutherian ancestral karyotype

Proc. Natl. Acad. Sci. USA

(2003)

U. Köhler et al.

Genomic reorganization and disrupted chromosomal synteny in the siamang (Hylobates syndactylus) revealed by fluorescence in situ hybridization

Am. J. Phys. Anthropol.

(1995)

M. Schmid et al.

First report on chicken genes and chromosomes 2000

Cytogenet. Cell Genet.

(2000)

I.G. Woods et al.

A comparative map of the zebrafish genome

Genome Res.

(2000)

F. Grützner et al.

Four-hundred million years of conserved synteny of human Xp and Xq genes on three Tetraodon chromosomes

Genome Res.

(2002)

J.A. Bailey et al.

Segmental duplications: organization and impact within the current Human Genome Project assembly

Genome Res.

(2001)

J.A. Bailey et al.

Recent segmental duplications in the human genome

Science

(2002)

A. Fujiyama et al.

Construction and analysis of a human–chimpanzee comparative clone map

Science

(2002)

Cited by (22)

Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice
2006, Genomics
Expression of Robo receptor molecules is important for axon guidance across the midline of the mammalian central nervous system. Here we describe novel isoform a of human ROBO2, which is initially strongly expressed in the fetal human brain but thereafter only weakly expressed in adult brain and a few other tissues. The known isoform b of ROBO2 shows a more or less ubiquitous expression pattern, suggesting diverse functional roles. The genomic structure and distinct expression patterns of Robo2a and Robo2b have been conserved in the mouse, but in contrast to human ROBO2a mouse Robo2a is also abundant in adult brain. Exons 1 and 2 of human ROBO2a lie in an inherently unstable DNA segment at human chromosome 3p12.3 that is associated with segmental duplications, independent chromosome rearrangements during primate evolution, and homozygous deletion and loss of heterozygosity in various human cancers. The 5′ end of mouse Robo2a lies in a <150-kb DNA segment of break in synteny between mouse chromosome 16C3.1 and the human genome.
Role of selection in fixation of gene duplications
2006, Journal of Theoretical Biology
New genes commonly appear through complete or partial duplications of pre-existing genes. Duplications of long DNA segments are constantly produced by rare mutations, may become fixed in a population by selection or random drift, and are subject to divergent evolution of the paralogous sequences after fixation, although gene conversion can impede this process. New data shed some light on each of these processes. Mutations which involve duplications can occur through at least two different mechanisms, backward strand slippage during DNA replication and unequal crossing-over. The background rate of duplication of a complete gene in humans is 10⁻⁹–10⁻¹⁰ per generation, although many genes located within hot-spots of large-scale mutation are duplicated much more often. Many gene duplications affect fitness strongly, and are responsible, through gene dosage effects, for a number of genetic diseases. However, high levels of intrapopulation polymorphism caused by presence or absence of long, gene-containing DNA segments imply that some duplications are not under strong selection. The polymorphism to fixation ratios appear to be approximately the same for gene duplications and for presumably selectively neutral nucleotide substitutions, which, according to the McDonald–Kreitman test, is consistent with selective neutrality of duplications. However, this pattern can also be due to negative selection against most of segregating duplications and positive selection for at least some duplications which become fixed. Patterns in post-fixation evolution of duplicated genes do not easily reveal the causes of fixations. Many gene duplications which became fixed recently in a variety of organisms were positively selected because the increased expression of the corresponding genes was beneficial. The effects of gene dosage provide a unified framework for studying all phases of the life history of a gene duplication. Application of well-known methods of evolutionary genetics to accumulating data on new, polymorphic, and fixed duplication will enhance our understanding of the role of natural selection in the evolution by gene duplication.
A rhesus macaque radiation hybrid map and comparative analysis with the human genome
2005, Genomics
The genomes of nonhuman primates are powerful references for better understanding the recent evolution of the human genome. Here we compare the order of 802 genomic markers mapped in a rhesus macaque (Macaca mulatta) radiation hybrid panel with the human genome, allowing for nearly complete cross-reference to the human genome at an average resolution of 3.5 Mb. At least 23 large-scale chromosomal rearrangements, mostly inversions, are needed to explain the changes in marker order between human and macaque. Analysis of the breakpoints flanking inverted chromosomal segments and estimation of their duplication divergence dates provide additional evidence implicating segmental duplications as a major mechanism of chromosomal rearrangement in recent primate evolution.
Comparative cytogenetics of human chromosome 3q21.3 reveals a hot spot for ectopic recombination in hominoid evolution
2005, Genomics
Fluorescence in situ hybridization mapping of fully integrated human BAC clones to primate chromosomes, combined with precise breakpoint localization by PCR analysis of flow-sorted chromosomes, was used to analyze the evolutionary rearrangements of the human 3q21.3-syntenic region in orangutan, siamang gibbon, and silvered-leaf monkey. Three independent evolutionary breakpoints were localized within a 230-kb segment contained in BACs RP11-93K22 and RP11-77P16. Approximately 200 kb of the human 3q21.3 sequence was not present on the homologous orangutan, siamang, and Old World monkey chromosomes, suggesting a genomic DNA insertion into the breakpoint region in the lineage leading to humans and African great apes. The breakpoints in the orangutan and siamang genomes were narrowed down to 12- and 20-kb DNA segments, respectively, which are enriched with endogenous retrovirus long terminal repeats and other repetitive elements. The inserted DNA segment represents part of an ancestral duplication. Paralogous sequence blocks were found at human 3q21, approximately 4 Mb proximal to the evolutionary breakpoint cluster region; at human 3p12.3, which contains an independent orangutan-specific breakpoint; and at the subtelomeric and pericentromeric regions of multiple human and orangutan chromosomes. The evolutionary breakpoint regions between human chromosome 3 and orangutan 2 as well their paralogous segments in the human genome coincide with breaks of chromosomal synteny in the mouse, rat, and/or chicken genomes. Collectively our data reveal reuse of the same short recombinogenic DNA segments in primate and vertebrate evolution, supporting a nonrandom breakage model of genome evolution.
Mammalian phylogenomics comes of age
2004, Trends in Genetics
The relatively new field of phylogenomics is beginning to reveal the potential of genomic data for evolutionary studies. As the cost of whole genome sequencing falls, anticipation of complete genome sequences from divergent species, reflecting the major lineages of modern mammals, is no longer a distant dream. In this article, we describe how comparative genomic data from mammals is progressing to resolve long-standing phylogenetic controversies, to refine dogma on how chromosomes evolve and to guide annotation of human and other vertebrate genomes.
The evolutionary history of human chromosome 7
2004, Genomics
We report on a comparative molecular cytogenetic and in silico study on evolutionary changes in human chromosome 7 homologs in all major primate lineages. The ancestral mammalian homologs comprise two chromosomes (7a and 7b/16p) and are conserved in carnivores. The subchromosomal organization of 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 then derived by a fission of 7b/16p, followed by a centric fusion of 7a/7b as observed in the orangutan. In hominoids two further inversions with four distinct breakpoints were described in detail: the pericentric inversion in the human/African ape ancestor and the paracentric inversion in the common ancestor of human and chimpanzee. FISH analysis employing BAC probes confined the 7p22.1 breakpoint of the pericentric inversion to 6.8 Mb on the human reference sequence map and the 7q22.1 breakpoint to 97.1 Mb. For the paracentric inversion the breakpoints were found in 7q11.23 between 76.1 and 76.3 Mb and in 7q22.1 at 101.9 Mb. All four breakpoints were flanked by large segmental duplications. Hybridization patterns of breakpoint-flanking BACs and the distribution of duplicons suggest their presence before the origin of both inversions. We propose a scenario by which segmental duplications may have been the cause rather than the result of these chromosome rearrangements.

View all citing articles on Scopus

View full text

Plasticity of human chromosome 3 during primate evolution

Abstract

Section snippets

Syntenic relationships of HSA 3 and PPY 2

Chromosome preparations

Acknowledgements

Genomics

Genomics

Genomics

Am. J. Hum. Genet.

Am. J. Hum. Genet.

Genomics

Am. J. Hum. Genet.

Genomics

Curr. Opin. Genet. Dev.

Genomics

Trends Genet.

Am. J. Hum. Genet.

Genomics

Ancestral primate viewed

Nature

Emerging patterns of comparative genome organization in some mammalian species as revealed by Zoo-FISH

Genome Res.

Reciprocal chromosome painting among human, aardvark, and elephant (superorder Afrotheria) reveals the likely eutherian ancestral karyotype

Proc. Natl. Acad. Sci. USA

Genomic reorganization and disrupted chromosomal synteny in the siamang (Hylobates syndactylus) revealed by fluorescence in situ hybridization

Am. J. Phys. Anthropol.

First report on chicken genes and chromosomes 2000

Cytogenet. Cell Genet.

A comparative map of the zebrafish genome

Genome Res.

Four-hundred million years of conserved synteny of human Xp and Xq genes on three Tetraodon chromosomes

Genome Res.

Segmental duplications: organization and impact within the current Human Genome Project assembly

Genome Res.

Recent segmental duplications in the human genome

Science

Construction and analysis of a human–chimpanzee comparative clone map

Science