Chromosomes 21 and 22: Gene Density

Abstract

Isochores are long DNA (deoxyribonucleic acid) segments that are fairly homogeneous in base composition. The GC (guanine+cytosine)‐richest and GC‐poorest isochores of the genomes from warm‐blooded vertebrates are characterised by the highest and the lowest gene concentrations, respectively. They correspond to specific types of chromosomal bands, namely the GC‐richest isochores are in the subset of R‐positive bands generally located at the telomeric chromosomal end and the GC‐poorest are in the darker G‐positive bands. The distribution of the isochores along the chromosomes determines the formation of the light/dark G/R bands, with the compositional difference at the local level having a great relevance. Chromosomes 21 and 22 can be used to show some properties of both the GC‐richest and GC‐poorest isochores of the human genome, being composed by chromosomal bands covering the entire range of GC composition, from the GC‐poorest L1+ bands to the GC‐richest H3+ bands.

Key Concepts

  • The human genome is composed of two compartments endowed with very different genomic properties.
  • The GC‐richest genomic compartment is prevalently composed of isochores from the H2 and H3 families.
  • The GC‐poorest genomic compartment is prevalently composed of isochores from the L1 family.
  • The GC‐richest and the GC‐poorest genomic compartments are located, in the mitotic chromosomes, distantly from one another.
  • The GC‐richest and the GC‐poorest genomic compartments correspond to the gene‐richest and the gene‐poorest region, respectively.
  • The GC‐richest and the GC‐poorest genomic compartments are located in the inner part and at the periphery of the cell nuclei.
  • Human chromosomes 21 and 22 summarise all the properties endowed with the GC‐richest and the GC‐poorest regions.

Keywords: isochores; GC level; chromosome bands; gene density; SINEs

Figure 1. GC (guanine+cytosine) level profiles of chromosomes 21 and 22. GC level of 300 kb nonoverlapping segments (average of the GC level from the corresponding 20 kb subwindows) from the long arm of chromosomes 21 and 22. The standard deviation is indicated for each of the 300 kb DNA (deoxyribonucleic acid) segments. A and B indicate the chromosomal regions (3 Mb in size) shown in Figure in more detail. The yellow area represents the intermediate compositional regions, namely the DNA regions, composed of L2 and H1 isochores, separating the GC‐richer H2/H3 and the GC‐poorer L1 isochores. Two evident band borders are indicated by arrows (see Figure for details). L1, L2, H1, H2 and H3 are the isochores belonging to the light GC‐poor families 1 and 2 and the heavy GC‐rich families 1, 2 and 3, respectively.
Figure 2. Compositional features of bands from chromosomes 21 and 22. (Bottom to top) Bands, ideograms showing the H3+, H3, L1 and L1+ bands. GC%, average GC level of each chromosomal band (horizontal blue lines), and GC levels observed at band borders (red and blue arrows indicate the GC level on the R and G band sides, respectively; vertical red lines indicate the GC difference over 300 kb regions around band borders). All G bands (L1+ or L1 bands) show lower GC levels than the adjacent R bands (H3+ or H3 bands), and all the R bands (H3+ or H3 bands) show higher GC levels than the adjacent G bands (L1+ or L1 bands). Note that the sizes of the two chromosomes were scaled according to the cytogenetic ideograms of Francke . H3+ and H3 are the R bands containing or not containing, respectively, the GC‐richest H3 isochores. L1+ and L1 are the G bands containing or not containing, respectively, the GC‐poorest L1 isochores. Modified from Chromosome Research, Genes, isochores and bands in human chromosomes 21 and 22. Chromosome Research, 9, 2001, 533–539, Saccone S, Pavlicek A, Federico C, Paces J and Bernardi G with permission of Springer.
Figure 3. Gene density at the chromosomal band level. (a) Distribution of genes in chromosomes 21 and 22 showing the very different gene density between the L1+ and the H3+ bands. (b) Plot showing the correlation between the average GC level of each band (from chromosomes 21 and 22) and the relative gene density. Three points, indicated by arrows, represent three outliers (two L1 and one H3+ bands) not taken into consideration when drawing the regression line. Inclusion of these points does not significantly change the lower slope and changes the higher slope only slightly. H3+ and H3 are the R bands containing or not containing, respectively, the GC‐richest H3 isochores. L1+ and L1 are the G bands containing or not containing, respectively, the GC‐poorest L1 isochores. Modified from Chromosome Research, Genes, isochores and bands in human chromosomes 21 and 22. Chromosome Research, 9, 2001, 533–539, Saccone S, Pavlicek A, Federico C, Paces J and Bernardi G with permission of Springer.
Figure 4. GC level‐related properties in two compositionally different genomic regions. (a) and (b) show, at higher resolution, the DNA regions indicated in Figure. Upper panels: Average GC‐level profiles of the 20 kb nonoverlapping windows that form each DNA region. The yellow areas indicate the intermediate compositional regions. The horizontal broken line is the lower limit of the GC‐richest H3 isochores. Bottom panels: At different levels of resolution, gene and repeated sequence contents are shown for each chromosomal region (from the UCSC Human Genome Browser http://genome.ucsc.edu/). Each gene is indicated by vertical (exons) and horizontal (introns) lines. BP, base position, indicating nucleotides from the short arm telomere; Genes Kn., indicate the known protein‐coding genes; Pr., indicate the Fgenesh++ prediction based on Softberry's gene‐finding software (see UCSC Human Genome Browser http://genome.ucsc.edu/); SINEs and LINEs, location of these repeats in the sequence. Printed from http://genome.ucsc.edu/.
close

References

Bernardi G, Olofsson B, Filipski J, et al. (1985) The mosaic genome of warm‐blooded vertebrates. Science 228: 953–958.

Bernardi G (2015) Chromosome architecture and genome organization. PLoS One 2015: 10. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143739.

Federico C, Andreozzi L, Saccone S and Bernardi G (2000) Gene density in the Giemsa bands of human chromosomes. Chromosome Research 8: 737–746.

Federico C, Cantarella CD, Di Mare P, Tosi S and Saccone S (2008) The radial arrangement of the human chromosome 7 in the lymphocyte cell nucleus is associated with chromosomal band gene density. Chromosoma 117: 399–410. DOI: 10.1007/s00412-008-0160-x.

Federico C, Pappalardo AM, Ferrito V, Tosi S and Saccone S (2017) Genomic properties of chromosomal bands are linked to evolutionary rearrangements and new centromere formation in primates. Chromosome Research 25: 261–276. DOI: 10.1007/s10577-017-9560-1.

Francke U (1994) Digitized and differentially shaded human chromosome ideograms for genomic applications. Cytogenetics and Cell Genetics 6: 206–219.

Fukagawa T, Sugaya K, Matsumoto K, et al. (1995) A boundary of long‐range G+C% mosaic domains in the human MHC locus: pseudoautosomal boundary‐like sequence exists near the boundary. Genomics 25: 184–191.

Saccone S, Federico C, Solovei I, et al. (1999) Identification of the gene‐richest bands in human prometaphase chromosomes. Chromosome Research 7: 379–386.

Saccone S, Pavlicek A, Federico C, Paces J and Bernardi G (2001) Genes, isochores and bands in human chromosomes 21 and 22. Chromosome Research 9: 533–539.

Saccone S, Federico C and Bernardi G (2002) Localization of the gene‐richest and the gene‐poorest isochores in the interphase nuclei of mammals and birds. Gene 300: 169–178.

Smit AF (1996) The origin of interspersed repeats in the human genome. Current Opinion in Genetics and Development 6: 743–748.

Soriano P, Meunier‐Rotival M and Bernardi G (1983) The distribution of interspersed repeats is non‐uniform and conserved in the mouse and human genomes. Proceedings of the National Academy of Sciences of the United States of America 80: 1816–1820.

Zoubak S, Clay O and Bernardi G (1996) The gene distribution of the human genome. Gene 174: 95–102.

Further Reading

Comings DE (1978) Mechanisms of chromosome banding and implications for chromosome structure. Annual Review of Genetics 12: 25–46.

Costantini M, Clay O, Federico C, et al. (2007) Human chromosomal bands: nested structure, high definition map and molecular basis. Chromosoma 116: 36–49.

Marshall OJ, Chueh AC, Wong LH and Choo KH (2008) Neocentromeres: new insights into centromere structure, disease development, and karyotype evolution. American Journal of Human Genetics 82: 261–282. DOI: 10.1016/j.ajhg.2007.11.009.

Stanyon R, RocchiM CO, Roberto R, et al. (2008) Primate chromosome evolution: ancestral karyotypes, marker order and neocentromeres. Chromosome Research 16: 17–39.

Watanabe Y and Maekawa M (2013) R/G‐band boundaries: genomicinstability and human disease. Clinica Chimica Acta 419: 108–112. DOI: 10.1016/j.cca.2013.02.011.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Saccone, Salvatore, and Bernardi, Giorgio(Jan 2018) Chromosomes 21 and 22: Gene Density. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005013.pub2]