Welcome to Part 3 of Bio 219

1. Welcome to Part 3 of Bio 219 Lecturer – David Ray Contact info: Office hours – 1:00-2:00 pm MTW Office location – LSB 5102 Office phone – 293-5102 ext 31454 E-mail – david.ray@mail.wvu.edu Lectures are available online at http://www.as.wvu.edu/~dray go to ‘Teaching’ link

2. How Genes and Genomes Evolve

3. Variation • There is obviously variation among and within taxa. • How does the variation arise in genomes? • Are there patterns to the variation? • How is the variation propagated? • What questions can be addressed using the variation? • What patterns exist in humans with regard to genomic variability?

4. Generating Genetic Variation • Somatic vs. germ line cells • Somatic cells – “body” cells, no long term descendants, live only to help germ cells perform their function. • Germ cells – reproductive cells, give rise to descendants in the next generation of organisms.

6. Generating Genetic Variation • Somatic vs. germ line mutations • Somatic mutations – occur in somatic cells and will only effect those cells and their progeny, cannot not be passed on to subsequent generations of organisms. • Germ mutations – can be passed on to subsequent generations.

8. Generating Genetic Variation • Five types of change contribute to evolution. • Mutation within a gene • Gene duplication • Gene deletion • Exon shuffling • Horizontal transfer – rare in Eukaryotes

10. Generating Genetic Variation • Most changes to a genome are caused by mistakes in the normal process of copying and maintaining genomic DNA.

11. Generating Genetic Variation • Mutations within genes • Point mutations – errors in replication at individual nucleotide sites occur at a rate of about 10-10 in the human genome. • Most point mutations have no effect on the function of the genome – are selectively neutral.

12. Generating Genetic Variation • DNA duplications • Slipped strand mispairing • Unequal crossover during recombination

15. Generating Genetic Variation • Gene duplication allows for the acquisition of new functional genes in the genome

17. Generating Genetic Variation • Gene Duplication: the globin family • A classic example of gene duplication and evolution • Globin molecules are involved in carrying oxygen in multicellular organisms • Ancestral globin gene (present in primitive animals) was duplicated ~500 mya. • Mutations accumulated in both genes to differentiate them - α and β present in all higher vertebrates • Further gene duplications produced alternative forms in mammals and in primates

18. Primates Mammals

19. Generating Genetic Variation • Gene Duplication • Almost every gene in the vertebrate genome exists in multiple copies • Gene duplication allows for new functions to arise without having to start from scratch • Studies suggest the early in vertebrate evolution the entire genome was duplicated at least twice

20. Generating Genetic Variation • Exon Duplication • Duplications are not limited to entire genes • Proteins are often collections of distinct amino acid domains that are encoded by individual exons in a gene • The separation of exons by introns facilitates the duplication of exons and individual gene evolution

22. Generating Genetic Variation • Exon Shuffling • The exons of genes can sometimes be thought of as individual useful units that can be mixed and matched through exon shuffling to generate new, useful combinations

24. Review from last week • Overall theme – There are lots of ways to create genetic variation. Genetic variation is the basis of evolutionary change but the variation must be introduced into the germ line to contribute to evolutionary change. • Two cell lines in multicellular organisms • Somatic – short term genetic repository • Germ line – long term genetic repository • Variation that occurs in the germ line are the only ones that can contribute to evolutionary change • Genetic variation can be accumulated through various events • Mutations in genes – point mutations • DNA duplications – microsatellites (small), unequal crossover (large) • Gene and exon duplications are the major method for generating new gene functions • Exon shuffling can produce new gene functions by creating new combinations of functional exons/protein domains

25. Generating Genetic Variation • Mobile elements contribute to genome evolution in several ways • Exon shuffling • Insertion mutagenesis • Homologous and non-homologous recombination

26. Generating Genetic Variation • What are mobile elements and how do they work? • Fragments of DNA that can copy itself and insert those copies back into the genome • Found in most eukaryotic genomes • Humans – Alu (SINE); Ta, PreTa (LINEs); SVA; plus several families that are no longer active

27. Pol III transcription Generating Genetic Variation: Normal SINE mobilization Reverse transcription and insertion 1. Usually a single ‘master’ copy 2. Pol III transcription to an RNA intermediate 3. Target primed reverse transcription (TPRT) – enzymatic machinery provided by LINEs

28. Generating Genetic Variation • Mobile elements contribute to genome evolution in several ways • Exon shuffling

29. SINE exon 2 Generating Genetic Variation: Exon shuffling via SINE mobilization exon 1 SINE exon 2 intron DNA copy of transcript SINE transcription can extend past the normal stop signal Reverse transcription creates DNA copies of both the SINE and exon 2 Reinsertion occurs elsewhere in the genome

30. Generating Genetic Variation • Mobile elements contribute to genome evolution in several ways • Exon shuffling • Insertion mutagenesis • The insertion of mobile elements can disrupt gene structure and function

31. Generating Genetic Variation

33. Generating Genetic Variation • Gene expression alteration via a P-element mobilization in Drosophila

34. Generating Genetic Variation • Mobile elements contribute to genome evolution in several ways • Exon shuffling • Insertion mutagenesis • The insertion of mobile elements can disrupt gene structure and function • Homologous and non homologous recombination • 10,000 – 1,000,000 + nearly identical DNA fragments scattered throughout the genome

35. Generating Genetic Variation Unequal crossover due to non-homologous recombination

38. Generating Genetic Variation • Gene transfer can move genes between entire genomes • Horizontal gene transfer • Main problem with the development of drug resistant strains of bacteria

39. Generating Genetic Variation • Bacterial conjugation

40. Reconstructing Life’s Tree • Evolutionary theory predicts that organisms that are derived from a common ancestor will share genetic signatures • Organisms that shared an ancestor more recently will be more similar than those that shared a more distant common ancestor • Similarity can include sequence composition, genome organization, presence/absence of mobile elements, presence/absence of gene families, etc.

41. 09_15_Phylogen.trees.jpg

42. 09_16_Ancestral.gene.jpg

43. 09_22_genetic.info.jpg

44. 09_17_Human_chimp.jpg Chromosome 1

45. Review from last time • Overall themes: Genetic variation can be introduced due to the activities and presence of mobile elements (MEs); Genetic information can be introduced into organisms through horizontal transfer. • MEs are fragments of DNA that can make copies of themselves and insert those copies back into the genome • MEs can lead to variation through exon shuffling, insertion mutagenisis, and recombination • Many human diseases are the result of MEs • Horizontal transfer can introduce genetic variation into bacteria via the process of conjugation • Introduction of concepts for discussion of “Reconstructing life’s tree” • All sorts of variation provide information on the relationships among organisms • Homology – derived from the same ancestral source • Phylogeny – a reconstruction of relationships based on observations

46. Reconstructing Life’s Tree • Basic terms • Homologous – derived from a common ancestral source • Phylogeny – a reconstruction of relationships based on observed patterns

47. Reconstructing Life’s Tree • Homologous genes can be recognized over large amounts of evolutionary time

48. Reconstructing Life’s Tree • Homologous genes can be recognized over large amounts of evolutionary time • Why? • Selectively advantageous genes and sequences tend to be conserved (preserved) • Selectively disadvantageous genes and sequences are tend not to be passed on to offspring

49. Reconstructing Life’s Tree • Most DNA of most genomes is non-coding • Changes to much of this DNA are selectively neutral – cause no harm or good to the genome • Different portions of the genome will therefore diverge at different rates depending on their function The neutral regions tend to change in a clock-like fashion • We can estimate divergence times for certain groups