Part 2. Genome Anatomies Chapter 7. Eukaryotic nuclear genomes Chapter 8. Genomes of prokaryotes and eukaryotic organelles Chapter 9. virus genomes and mobile genetic elements

Chapter 7. Eukaryotic nuclear genomes

7.1. Nuclear genomes are contained in chromosomes Chromosome number is unrelated to biological features of the organism. Yeast (16), fruit fly(4). Nor is chromosome number linked to genome size (some salamanders have genomes 30 times bigger than human but about half the number of chromosomes) How do chromosome number change? An unexpected way. Saccharomyces cerevisiae (budding yeast, brewer’s yeast, distiller’s yeast or wine yeast, ) Schizosaccharomyces pombe (fission yeast)

7.1.1 Packaging of DNA into chromosome

Nucleosome and higher level package

Something new Tilgner, H. et al. Nucleosome positioning as a determinant of exon recognition. Nature Struct. Mol. Biol. 16, 996–1001 (2009) Schwartz, S. et al. Chromatin organization marks exon–intron structure. Nature Struct. Mol. Biol. 16, 990–995 (2009) Andersson, R. et al. Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res. 19, 1732-41 (2009). When chromatin meets splicing. Nature Struct. Mol. Biol. 16, 902 - 903 (2009) Chromatin: A peak for exons. Nature Rev. Genet. 10, 664-665 (October 2009)

Something New The long-standing view of chromosome packaging is that 10-nm beads-on-a string chromatin fibres fold into higherorder 30-nm fibres, which further twist and coil to form highly condensed chromosomes. Nishino et al (2012) demonstrates that regular 30-nm fibres are absent from human mitotic chromosomes. The emerging view is that chromosome-level condensation can be achieved through packaging of 10-nm fibres in a fractal manner. 1. Hansen JC: Human mitotic chromosome structure: what happened to the 30-nm fibre? EMBO J 2012, 31:1621-1623. 2. Nishino Y, et al.: Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure. EMBO J 2012, 31:1644-1653.

The typical appearance of a metaphase chromosome

Untypical chromosomes Minichromosomes and macrochromosomes B chromosomes Holocentric chromosomes，in Caenorhabditis elegans Heterochromatin: not totally silenced.

Arabidopsis centromeres span 0. 9-1 Arabidopsis centromeres span 0.9-1.2 Mb of DNA and each one is made up largely of 180-bp repeat sequences. In humans the equivalent sequences are 171 bp and are called alphoid DNA. The special centromeric proteins in humans include at least seven that are not found elsewhere in the chromosome Telomeric DNA is made up of hundreds of copies of a repeated motif, 5-TTAGGG-3 in humans. It critical to the survival of the chromosome and may be a key to understanding cell senescence and death. See the Nobel price 2009.

7. 2 The genetic features of eukaryotic nuclear genome 7. 2 7.2 The genetic features of eukaryotic nuclear genome 7.2.1 Where are the genes in a nuclear genome?

isochore

Isochore and gene density

7.2.2 How are the genes organized in a nuclear genome The genes make up only a small part of the human genome. The yeast genome and other small organisms (especially for symbiotic organisms) are very compact.

A segment of the human genome

The composition of the human genome

Genome size

C-value paradox

原生生物界 真菌界 植物界 哺乳动物 其他脊椎动物 无脊椎动物

Compactness of the yeast, fruit-fly and human genomes

A comparison among species

Previous milestone work: Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA (2002) Selection for short introns in highly expressed genes. Nature Genetics 31: 415-418.

发展中国家的穷实验室如何发展？ 没钱，但我们有时间。静下心来，多读一些文献，还是能找到省钱的课题。建议大家多翻翻Nature, Science, Nature Genetics, PNAS, Current Biology, Genome Research这几种高级别杂志，至少我发现了很多论文不用花多少钱，属于脑力密集型研究，关键是新颖的思路和丰富的背景知识。 哪个领域富于脑力密集型科研项目呢？ 生物信息学和比较基因组学。

Where are the genes in a eukaryotic genome? In most organisms, genes appear to be distributed more at less at random (really?), with substantial variations in gene density at different positions within a chromosome. Recent study: expression-position, GC content, gene density, intron length expression level, and SINE density

7.2.3 How many genes are there and what are their functions

Categorization of the human gene catalog Gene Ontology

Comparison of the gene catalogs

Protein domains

Families of genes Ribosomal genes are present in multiple copies because there is a heavy demand for rRNA synthesis during cell division, when several tens of thousands of new ribosomes must be assembled. The globin genes are expressed at different stages in human development. The different biochemical properties of the resulting globin proteins are thought to reflect slight changes in the physiological role that hemoglobin plays during the course of human development.

Pseudogenes and other evolutionary relics Conventional pseudogene Processed pseudogene Pseudogenes may be backup genetic information.

7.2.4 The repetitive DNA content of eukaryotic nuclear genomes Junk DNA

Tandemly repeated DNA, also called satellite DNA Minisatellites Microsatellites---although their function, if any, is known, they have been proved very useful to geneticists.

No two individuals have the same genetic profile because each person has a different set of microsatellite length variants, which give rise to bands of different size.

Further Reading Hurst, L. D. et al. 2004. The evolutionary dynamics of eukaryotic gene order. Nat. Rev. Genet. 5:299-310. Szekvolgyi, L. et al. 2007. Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA. PNAS 104:14964-14969. Our data imply that the double-stranded genomic DNA is composed of contiguous rather than continuous single strands and reveal an aspect of higher-order chromatin organization with ribonucleoprotein-associated persistent nicks defining {approx}50-kbp domains. Satou, Y. et al. 2008. Improved genome assembly and evidence-based global gene model set for the chordate Ciona intestinalis: new insight into intron and operon populations. Genome Biol. 2008, 9:R152. ~20% of Ciona genes reside in operons and that operons contain a high proportion of single-exon genes Zheng D, Gerstein MB: The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends Genet 2007, 23:219-224.