Chapter 21: Genomes & Their Evolution

Transcription

1 Chapter 21: Genomes & Their Evolution 1. Sequencing & Analyzing Genomes 2. How Genomes Evolve

2 1. Sequencing & Analyzing Genomes Chapter Reading pp

3 Whole Genome Shotgun Sequencing 1 Cut the DNA into overlapping fragments short enough for sequencing. 2 Clone the fragments in plasmid or phage vectors. 3 Sequence each fragment. 4 Order the sequences into one overall sequence with computer software.

4 Bioinformatics Bioinformatics refers to application of statistics and computer analysis to DNA, protein sequence data. computer analysis can identify protein coding regions in DNA, determine amino acid sequences, compare sequences among species, etc

5 Relative Genome Size Genome size and gene number do not correlate at all with organism complexity. alternative splicing of genes and the repertoire of noncoding RNAs (e.g., mirna) may be a better indicator of sophistication or complexity in a species

6 Types of Human DNA Elements Most of the human genome (and that of many other species) does not code for any obvious gene products and has a function that is as yet unclear.

7 Repetitive DNA Elements Much of the human genome consists of repetitive DNA sequences that are thought to ultimately be of viral origin. Transposable Elements DNA segments that are duplicated and distributed throughout the genome Alu elements repetitive DNA sequences containing the Alu I restriction enzyme sites Short tandem repeats (STRs) very short sequences repeated over and over

8 Transposable Elements Barbara McClintock proposed the concept of jumping genes in the 1950s based on her studies of corn which was not taken seriously. Much later the existence of transposable elements that could jump in the genome validated her observations.

9 Transposons Transposon New copy of transposon DNA of genome Transposon is copied Insertion Mobile transposon Mobile DNA elements that can be copied & inserted Elsewhere in the genome. the transposon encodes the enzyme transposase which can copy transposon sequence and randomly insert elsewhere

10 Retrotransposons Retrotransposons are much like transposons except that they encode reverse transcriptase and have an RNA intermediate in the process. Retrotransposon New copy of retrotransposon Formation of a single-stranded RNA intermediate Reverse transcriptase RNA Insertion

11 Multigene Families Many genes are actually part of a group or cluster of similar genes referred to as a multigene family. 2 or more genes with nearly identical or very similar sequences thought to have arisen due to gene duplication and subsequent mutation members of a multigene family are typically similar in function as well as sequence arrangement of genes in multigene families also provides evidence of similar origins

12 b-globin a-globin Heme a-globin gene family Chromosome 16 b-globin gene family Chromosome 11 z y z ya 2 y a 1 a 2 a 1 y q e G g A g y b d b Embryo Fetus and adult Embryo Fetus Adult (b) The human a-globin and b-globin gene families

13 2. How Genomes Evolve Chapter Reading pp

14 Rearrangement of Genomes Genomes can undergo a number of large-scale changes that can lead to significant changes in genetic structure and in gene products: Chromosomal rearrangement breaking and recombining of pieces of diff. chrom. Transposition of mobile DNA elements sequences that can move around the genome Gene duplication duplication of gene sequences Exon shuffling combining of exons from different genes

15 Changes in Chromosome Structure Human chromosome 2 is clearly a combination of chimpanzee chromosomes 12 & 13. Telomere sequences Centromere sequences Human chromosome 2 Chimpanzee chromosomes Blocks of genes in mice and humans have remained intact though they are distributed differently among chromosomes. Telomere-like sequences Centromere-like sequences 12 Human chromosome 16 Mouse chromosomes (a) Human and chimpanzee chromosomes (b) Human and mouse chromosomes

16 Evolution of Novel Genes Genes encoding proteins with entirely new functions can arise by: 1) Duplication of existing gene followed by mutation producing distinct gene product the 2 genes will share significant homology however may have very different functions (e.g., lysozyme and a-lactalbumin) 2) Exon shuffling errors in meiotic recombination or transposition can cause the addition or loss of exons from similar or very different genes

17 Gene Duplication & Crossing Over Incorrect pairing of two homologs during meiosis Nonsister chromatids Gene Crossover point Transposable element Misalignment of similar DNA sequences during meiotic crossing over can result in chromosomes with duplicated (or missing) regions of DNA. and

18 Duplication followed by Mutation lysozyme vs a-lactalbumin

19 Model for Globin Gene Duplication The globin gene families show evidence of duplication. Duplication of ancestral gene Ancestral globin gene Evolutionary time Mutation in both copies Transposition to different chromosomes Further duplications and mutations z a a a b e b g b z y z y a y a a 2 a 1 y q e Gg Ag y b d b 2 1 a-globin gene family on chromosome 16 b-globin gene family on chromosome 11

20 Globin Gene Comparison Over time apparently duplicated globin genes diverged via mutation into similar yet distinct proteins with similar yet unique functions.

21 Exon Shuffling EGF EGF EGF EGF Epidermal growth factor gene with multiple EGF exons F F F F Fibronectin gene with multiple finger exons Exon shuffling Exon duplication F EGF K K K Plasminogen gene with a kringle exon Exon shuffling Portions of ancestral genes TPA gene as it exists today

22 Comparing Genomes Most recent common ancestor of all living things Billions of years ago 1 0 Bacteria Eukarya Archaea Sequence homology and genome structure reflect evolutionary relatedness: Millions of years ago 10 Chimpanzee Human Mouse 0 degree of differences in gene sequences, chromosome & gene structures allow estimation of time since a common ancestor

23 Key Terms for Chapter 21 whole genome shotgun seq. bioinformatics transposable elements: transposons, transposase, retrotransposons gene duplication, exon shuffling Relevant Chapter Questions: 1-6