How Genes and Genomes Evolve Ch 09

Generating genetic variation

09_01_Germ_somatic1.jpg 09_01_Germ_somatic1.jpg

09_02_Germ_somatic2.jpg 09_02_Germ_somatic2.jpg

09_03_altered.genes.jpg nt change, delete, duplication DNA replication, repair creating a set of closely related genes within a single cell chromosome breakage, repair 09_03_altered.genes_Part1.jpg breaking and rejoining within intron sequences of genes does not have to be precise to result in a functional gene

Figure 9-3 Part 2 (intercellular gene transfer) 09_03_altered.genes_Part2.jpg rare among eucaryotes, common among procaryotes

point mutations mutation frequencies: in E. coli: 1 nt change per 109 nt pairs per cell generation in human: 0.1 nt change per 109 nt pairs each time the DNA is copied

point mutations provide a way of fine tuning the function of a gene by making small adjustments to its sequence can also eliminate the activity of genes very often, however, point mutations do neither of these things; at many sites in the genome, a point mutation has absolutely no effect on the appearance or viability of the organism.

silent, selectively neutral mutations the mutations leads to no alteration in the A.A. sequence of any protein, or in the function of any regulatory piece of DNA. such mutations accumulate steadily in the genome of a species over evolutionary time, can be used like the ticks of an evolutionary clock to estimate how many generations separate two individuals, or two closely related species, from their last common ancestor

DNA duplications give rise to families of related genes within a single cell gene duplication and divergence: generating new genes giving rise to families of related genes within a single cell ex: Bacillus subtilis genome- eucaryotic genomes- opsins, collagens, globins, … different opsins- detecting light of different wavelengths, are expressed in different retinal cell different collagens- are expressed in the various types of connective tissue globins- increase carrying efficiency of oxygen

09_04_Bac.subtilis.jpg Bacillus subtilis genome- contains many families of evolutionarily related genes 09_04_Bac.subtilis.jpg Largest gene family: the “ABC transporters” contains 77 genes ABC transporters: a class of proteins that transport various materials across the cell membrane gene duplications and divergence give rise to families of related genes within a single cell

09_05_Gene.duplicate.jpg (remnants of transposons) (homologous recombination)

09_06_globin.1.jpg 09_06_globin.1.jpg cooperative allosteric change

The globin gene family Oxygen-binding proteins The most primitive oxygen-carrying molecule in animal: a globin polypeptide of ~150 aa (marine worms, insects, primitive fish) The hemoglobin molecule: in higher vertebrates (higher fish): composed of two kind of globin (α- and β-globin chain) in modern higher vertebrates: a complex of two α- and two β-globin chain (α2β2) in mammals…….

mammals primates β (adults) δ: (α2δ2)- in adults β ε: (α2ε2)- in early development stage β like (fetus) (higher affinity for O2) γG γ: (α2γ2)- in fetus in fetus γA each of these duplicated genes has been modified by point mutations affect the properties of the final hemoglobin molecule change in regulatory regions (gene expression at different times and with different levels when development) there are several duplicate globin DNA sequences in the α- and β-globin gene cluster

09_07_globin.2.jpg 09_07_globin.2.jpg

each of these duplicated genes has been modified by point mutations affect the properties of the final hemoglobin molecule change in regulatory regions (gene expression at different times and with different levels when development) there are several duplicate globin DNA sequences in the α- and β-globin gene cluster that are not functional genes, but pseudogenes

Gene duplication and divergence provide a critical source of genetic novelty for evolving organisms provide an organism with a cornucopia of spare gene copies, which are free to mutate to serve divergent purposes almost every gene in the genome of a vertebrate exists in multiple versions

09_08_Xenopus.jpg Xenopus tropicalis Whole-genome duplication, (diploid genome) Whole-genome duplication, All chromosome amplification Xenopus laevis 09_08_Xenopus.jpg (duplicated genome)

09_09_exon.jpg exon shuffling New genes can be generated by repeating the same exon (internal duplications) exon shuffling 09_09_exon.jpg long introns short exons many genes in eucaryotes are composed of a series of repeating protein domains, such as albumins, immunoglobulins, collagens, ……

09_10_Exon.shuffling.jpg New genes generated by exon shuffling exon shuffling can generate proteins with new combinations of protein domains. 09_10_Exon.shuffling.jpg domain: small discrete region of a structure A protein domain is a compact and stable folded region of polypeptide. (A membrane domain is a region of bilayer with a characteritistic lipid and protein composition.)

It has been proposed that all the proteins encoded by the human genome (~30000) arose from the duplication and shuffling of a few thousand distinct exons, each encoding a protein domain ~30-50 aa.

09_11_exon.arrange.jpg The evolution of genomes has been accelerated by the movement of transposable elements 09_11_exon.arrange.jpg is a frequent cause of spontaneous mutation p. 301

The activity of transposons can also change the way that existing genes are expressed. Ex: an insertion of a tansposon in the regulatory region of a gene Transposons are a significant source of developmental changes, and they are thought to have been particularly important in the evolution of the body plans of multicellular plants and animals.

09_12_Mutation.jpg 09_12_Mutation.jpg Mutation due to a transposable element can induce dramatic alterations in the body plan of an organism.

Horizontal gene transfer Genes are exchanged between organisms. This mechanism is rare among eucaryotes, but common among bacteria. Such genetic exchanges are currently responsible for the rise of new and potentially dangerous strains of drug-resistant bacteria.

09_13_conjugation.jpg 09_13_conjugation.jpg conjugation

09_14_promiscuous.jpg 09_14_promiscuous.jpg

Reconstructing life’s family tree

09_15_Phylogen.trees.jpg phylogenetic tree: (p. 306) *homologous genes: genes that are similar in their nucleotide sequence p304

09_16_Ancestral.gene.jpg 09_16_Ancestral.gene.jpg in the leptin gene, 5/441 nt differ between human and chimp

09_17_Human_chimp.jpg 09_17_Human_chimp.jpg

Alu retrotransposon has had only minor effects on the overall structure of human and chimp genomes. Most of the Alu sequences in our genome underwent duplication and transposition before humans and chimpanzees diverged.

06_35_L1 and Alu-like.jpg Alu L1 L1 B1 (~ human Alu) The positions of transposons in the human and the mouse genomes provide additional evidence of the long divergence time separating the two species.

Functionally important sequences show up as islands of DNA sequence conservation conserved synteny- (p. 307) regions where corresponding genes that began as neighbors have remained neighbors, strung together in the same sequence in both species

09_19_human_mouse1.jpg Coding sequence of exson is much more conserved than the intron sequence 09_19_human_mouse1.jpg Purifying selection: the elimination of individuals carrying mutations that interfere with important functions. exons, rRNA gene, regulatory proteins binding sites p. 308

09_20_puffer.fish.jpg Fugu rubripes genome size 400 million bp: ~1/4 of zebrafish; ~1/8 of human gene no., structure, position,…. almost the same with human… with the shortest intrones in all species

09_21_Fugu.introns.jpg Huntingtin gene contain 67 short exons that align in 1:1 correspondence with one another The human gene is 7.5 times larger than the Fugu gene, due entirely to the presence of larger intrones in the human sequence. The larger size of human intrones is a result in part of the presence of transposable elements. 09_21_Fugu.introns.jpg The positions of Fugu introns are conserved relative to their positions in mammalian genomes. The “junk DNA” is dispensable.

09_22_genetic.info.jpg Some genetic information has been conserved since the beginnings of life. (a part of the ss rRNA gene sequence) 09_22_genetic.info.jpg

09_23_tree.of.life.jpg Sequence conservation allows us to trace even the most distant evolutionary relationships The living world has three major divisions (domains) 09_23_tree.of.life.jpg (by ss rRNA gene sequences)

Examining the human genome

09_24_human.genome.jpg If each nt pair is drawn to span 1 mm, then the human genome would extended 3200 km 09_24_human.genome.jpg

Human genome Entire human genome- 3.2  109 nucleotide pairs 22 autosomes and 2 sex chromosomes Individual humans differ from one another by an average of 1 nucleotide in 1000

The human chromosome 22, one of the smallest human chromosomes The first human chromosome to have its nucleotide sequence determined

09_25_Chromosome22.jpg 09_25_Chromosome22.jpg

09_26_noncoding.jpg 09_26_noncoding.jpg regulatory DNA equences: are typically spread out over tens of thousands of nucleotide pairs, most of which is “spacer” DNA

Genetic variation within the human genome contributes to our individuality SNPs- single-nucleotide polymorphisms (p.313) single base changes in the same region of the genome from two different humans when the same region of the genome from two different humans is compared, the nucleotide sequences typically differ by about 0.1% more than 3 million SNPs had been located more than 90% of all human genes contain at least one SNP CA repeats- (p. 316)

09_27_Computer.prog.jpg Counting genes finding genes by computer programs 09_27_Computer.prog.jpg a DNA sequence of 7500 nucleotide pairs from Candida albicans

09_28_human_mouse2.jpg centromere human mouse The human and mouse genomes contain many regions where the order of genes has been preserved

09_29_developmental.jpg Regulatory genes and proteins define an organism’s developmental program 09_29_developmental.jpg

07_18_a_tropomyo.jpg alternative splicing ~60% human genes undergo alternative splicing

09_30_alt.splice.RNA.jpg alternative splicing of Drosophila DSCAM transcripts final mRNA transcript contains 23 exons 09_30_alt.splice.RNA.jpg 1A+1B+1C+1D+19 invariant exsons alternative splicing of RNA transcripts can produce many distinct proteins

06_28_Homol.recomb1.jpg 06_28_Homol.recomb1.jpg

06_29_Homol.recomb2.jpg 06_29_Homol.recomb2.jpg