The principal aim of the Human Genome Project was to obtain the (almost) complete sequence of the nuclear genome. Unlike mitochondrial DNA, chromosomal DNA molecules have regions with long clusters of consecutive repeated DNA sequences (tandem repeats) that are difficult to sequence (assembly of clone contigs across long regions of repetitive DNA is often a challenge). The constitutive heterochromatin of somatic cells is essentially devoid of genes, and it has very long clusters of repetitive DNA whose sequences are difficult to obtain.
Because of the above considerations, heterochromatin was accorded a low priority for DNA sequencing; the primary goal of the Human Genome Project was to sequence the euchromatin fraction of the genome. That meant, however, that essentially all genes would be sequenced. (A notable exception was the large arrays of tandemly repeated ribosomal RNA genes; that was not considered a problem because individual sequences had already been obtained for each of the different rRNA genes.) By 2003, a virtually complete sequence had been obtained for the euchromatic region of human DNA.
By summing the lengths of the DNA molecules in our 24 different chromosomes (22 autosomes, X and Y), the size of our nuclear genome is now estimated to be very close to 3.1 Gb (3100 Mb) in size, and currently approximately 40,000 human genes are recognized, as described below. That gives a comparatively low gene density of roughly one gene per 80 kb, and there is a very low percentage, about 1.1%, of coding DNA. By com parison, the 16.6 kb mitochondrial genome, like bacterial genomes, is packed with genes (with one gene per 450 bp, on average), and has a high proportion (66%) of coding DNA. The nuclear genome is also radically different from the mitochondrial genome in having a very large amount of repetitive DNA, which is especially prevalent in heterochromatin, but also very prominent in euchromatin. Note that unlike the mitochondrial genome, the chromosomal DNA molecules have large amounts of bound protein, both histones and non-histone proteins, and certain associated RNAs can serve structural roles too within the heterochromatic regions, as described below.
All egg cells, and sperm cells bearing an X chromosome, have a haploid genome of 3.04 Gb of DNA (3.1 Gb minus Y-chromosome DNA); sperm cells bearing a Y chromo some have a haploid genome of 2.94 Gb. Most somatic cells are diploid, having two copies of the nuclear genome, but have a much larger and more variable number of copies of the mitochondrial genome. Because the size of the nuclear genome is about 190,000 times the size of an mtDNA molecule, however, the nucleus of a human cell typically contains more than 99% of the DNA in the cell. (The oocyte is a notable exception: its 100,000 mtDNA molecules comprise a total of about 1.6 Gb of DNA, about one-third of the DNA in the cell.)
The DNA of human chromosomes varies considerably in length, from 249.7 Mb for chromosome 1 to 46.7 Mb for chromosome 21 (Table 1). There is also significant variability between chromosomes in the proportions of DNA underlying euchromatin and constitutive heterochromatin. Each chromosome has several megabases of heterochromatic DNA at the centromere, but many chromosomes also have significant amounts of non-centromeric heterochromatin. Thus, chromosomes 1, 9, 16, and 19 have substantial amounts of heterochromatin in regions close to the centromeres (pericentromeric heterochromatin)—see the chromosome banding figure in the inside back cover. The acrocentric chromosomes (having a centromere very close to one end of the chromo some; that is, chromosomes 13, 14, 15, 21, and 22) each have two sizeable heterochromatic regions in their short arms. But the Y chromosome has by far the largest proportion of heterochromatic DNA, with a particularly large segment of non-centromeric hetero chromatin on the long arm (see the figure on the inside back cover).
Table1. REFERENCE SEQUENCES AND SOME CHARACTERISTICS OF THE 24 HUMAN CHROMOSOMAL DNA MOLECULES
Table1. (Continued) REFERENCE SEQUENCES AND SOME CHARACTERISTICS OF THE 24 HUMAN CHROMOSOMAL DNA MOLECULES
