Genomes and their evolution Chapter 21 Genomes and their evolution

Genomics is the study of whole sets of genes and their interactions http://www.youtube.com/watch?v=mmgIClg0Y1k Bioinformatics is the application of computational methods to the storage and analysis of biological data http://www.youtube.com/watch?v=xODTm4a6nsM&feature=related

Overlapping fragments Figure 21.2-4 Chromosome bands Cytogenetic map Genes located by FISH 1 Linkage mapping Genetic markers 2 Physical mapping Figure 21.2 Three-stage approach to sequencing an entire genome. Overlapping fragments 3 DNA sequencing

Whole-Genome Shotgun Approach to Genome Sequencing The whole-genome shotgun approach was developed by J. Craig Venter in 1992 http://www.wiley.com/legacy/wileychi/reecegenes/chapter9_ani.html This approach skips genetic and physical mapping and sequences random DNA fragments directly Powerful computer programs are used to order fragments into a continuous sequence

Cut the DNA into overlapping frag- ments short enough for sequencing. Figure 21.3-3 1 Cut the DNA into overlapping frag- ments short enough for sequencing. 2 Clone the fragments in plasmid or phage vectors. 3 Sequence each fragment. Figure 21.3 Whole-genome shotgun approach to sequencing. 4 Order the sequences into one overall sequence with computer software.

Identifying Protein-Coding Genes and Understanding Their Functions Using available DNA sequences, geneticists can study genes directly in an approach called reverse genetics The identification of protein coding genes within DNA sequences in a database is called gene annotation Gene annotation is largely an automated process Comparison of sequences of previously unknown genes with those of known genes in other species may help provide clues about their function

Understanding Gene and Gene Expression at the Systems Level Proteomics is the systematic study of all proteins encoded by a genome Proteins, not genes, carry out most of the activities of the cell

Glutamate biosynthesis Figure 21.5 Glutamate biosynthesis Serine- related biosynthesis Translation and ribosomal functions Mitochondrial functions Vesicle fusion RNA processing Amino acid permease pathway Peroxisomal functions Transcription and chromatin- related functions Metabolism and amino acid biosynthesis Nuclear- cytoplasmic transport Figure 21.5 The systems biology approach to protein interactions. Nuclear migration and protein degradation Secretion and vesicle transport Mitosis Protein folding, glycosylation, and cell wall biosynthesis DNA replication and repair Cell polarity and morphogenesis

Table 21.1 Table 21.1 Genome Sizes and Estimated Numbers of Genes

Intergenic DNA is noncoding DNA found between genes About 25% of the human genome codes for introns and gene-related regulatory sequences (5%) Intergenic DNA is noncoding DNA found between genes Pseudogenes are former genes that have accumulated mutations and are nonfunctional Repetitive DNA is present in multiple copies in the genome About three-fourths of repetitive DNA is made up of transposable elements and sequences related to them

Regulatory sequences (20%) Figure 21.7 Exons (1.5%) Introns (5%) Regulatory sequences (20%) Repetitive DNA that includes transposable elements and related sequences (44%) Unique noncoding DNA (15%) L1 sequences (17%) Figure 21.7 Types of DNA sequences in the human genome. Repetitive DNA unrelated to transposable elements (14%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (56%)

Transposable Elements and Related Sequences The first evidence for mobile DNA segments came from geneticist Barbara McClintock’s breeding experiments with Indian corn McClintock identified changes in the color of corn kernels that made sense only by postulating that some genetic elements move from other genome locations into the genes for kernel color These transposable elements move from one site to another in a cell’s DNA; they are present in both prokaryotes and eukaryotes http://www.youtube.com/watch?v=_Ol492CLkdY

New copy of transposon Transposon is copied Figure 21.9 New copy of transposon Transposon DNA of genome Transposon is copied Insertion Figure 21.9 Transposon movement. Mobile transposon

New copy of retrotransposon Reverse transcriptase Figure 21.10 New copy of retrotransposon Retrotransposon Formation of a single-stranded RNA intermediate RNA Insertion Reverse transcriptase Figure 21.10 Retrotransposon movement.

Genes and Multigene Families Many eukaryotic genes are present in one copy per haploid set of chromosomes The rest of the genome occurs in multigene families, collections of identical or very similar genes Some multigene families consist of identical DNA sequences, usually clustered tandemly, such as those that code for rRNA products The classic examples of multigene families of nonidentical genes are two related families of genes that encode globins α-globins and β-globins are polypeptides of hemoglobin and are coded by genes on different human chromosomes and are expressed at different times in development

Nontranscribed spacer Transcription unit Figure 21.11 DNA RNA transcripts -Globin Nontranscribed spacer -Globin Transcription unit Heme DNA -Globin gene family -Globin gene family 18S 5.8S 28S Chromosome 16 Chromosome 11 rRNA 5.8S    2  1 G 2 1   A    28S Figure 21.11 Gene families. Fetus and adult 18S Embryo Embryo Fetus Adult (a) Part of the ribosomal RNA gene family (b) The human -globin and -globin gene families

Duplication, rearrangement, and mutation of DNA contribute to genome evolution The basis of change at the genomic level is mutation, which underlies much of genome evolution The earliest forms of life likely had a minimal number of genes, including only those necessary for survival and reproduction The size of genomes has increased over evolutionary time, with the extra genetic material providing raw material for gene diversification

Duplication of ancestral gene Figure 21.14 Ancestral globin gene Duplication of ancestral gene Mutation in both copies   Transposition to different chromosomes Evolutionary time   Further duplications and mutations      Figure 21.14 A model for the evolution of the human -globin and -globin gene families from a single ancestral globin gene.     2 1   G A    2 1 -Globin gene family on chromosome 16 -Globin gene family on chromosome 11

Exon shuffling Exon duplication Exon shuffling Figure 21.15 EGF EGF EGF EGF Epidermal growth factor gene with multiple EGF exons Exon shuffling Exon duplication F F F F Fibronectin gene with multiple “finger” exons F EGF K K Figure 21.15 Evolution of a new gene by exon shuffling. K Exon shuffling Plasminogen gene with a “kringle” exon Portions of ancestral genes TPA gene as it exists today

Most are 104,000 Mb, but a few are much larger Most are 16 Mb Figure 21.UN01 Bacteria Archaea Eukarya Genome size Most are 104,000 Mb, but a few are much larger Most are 16 Mb Number of genes 1,5007,500 5,00040,000 Gene density Lower than in prokaryotes (Within eukaryotes, lower density is correlated with larger genomes.) Higher than in eukaryotes Introns None in protein-coding genes Present in some genes Unicellular eukaryotes: present, but prevalent only in some species Multicellular eukaryotes: present in most genes Figure 21.UN01 Summary figure, Concept 21.3 Other noncoding DNA Can be large amounts; generally more repetitive noncoding DNA in multicellular eukaryotes Very little