1. Evolution of eukaryote genomes
Lecture 12: Evolution of introns

2. Eukaryotic Genomes
Bacteria have compact genomes rich in genes, having fewer noncoding regions and no introns. Eukaryotic genomes have much more DNA content than bacteria.
While eukaryotes have more genes than bacteria, the difference in gene content is not as great as the difference in DNA content: there is much more noncoding DNA in eukaryotes
In fact, gene-coding regions comprise only about 2% of the human genome.
Eukaryotic genes are interrupted by large introns. In eukaryotes, repeated sequences characterize great amounts of noncoding DNA.

4. Eukaryotic Genomes Cont….
The first eukaryotic organism to have its entire genome sequenced was yeast, Saccharomyces cerevisiae -1996
Yeast genome contains 5885 protein coding genes:
genes specifying ribosomal RNA (rRNA)
2. 40 genes for nuclear RNA molecules
3. over 200 transfer RNA (tRNA) genes
Deletion in some genes (18.7%) has a lethal effect while on other genes does not, due to many duplicated genes in the yeast genome
Genome sequences of other eukaryotic genomes soon followed:
1. Worm, Caenorbabditis elegans -1998
2. Fruit Fly, Drosophila melanogaster and plant model Arabidosis thaliana
3. Nearly complete Human Genome sequence-2004

5. Eukaryotic Genomes Cont….
Gene density varies among different eukaryotic species – ranging from 1gene/1900 bp in baker’s yeast to 1gene/ bp in humans
Species
1,300
4,300
1,900
4,900
9,500
4,500
127,900
1,996
5,317
6,268
20,516
13,792
25,706
22,287
2,497,519
22,820,308
12,057,909
100,291,841
131,000,899
116,566,763
2,851,330’913
Microsporidian
Malaria protozoan
baker’s yeast
roundworm
Fruit fly
Mouse ear cress
Human
Protists
Encephalitozoon cuniculi
Plasmodium falciparum
Fungi
Saccharomyces cerevisae
Nematode
Caemorhabditis elegans
Insects
Drosophila melanogaster
Plant
Arabidopsis thaliana
Vertebrates
Homo sapiens
Gene Density
(bp/gene)
Predicted number of genes
Genome Size in nucleotide pairs
Common Name
Table: Size and Predicted Gene Content of Selected Eukaryotic Genomes

6. Eukaryotic Genomes Cont….
Genomes of single-celled eukaryotes eg. yeast have one gene for every bp
Gene density decreases with the increased developmental complexity eg. gene density is the lowest in mammals i.e 1gene for every 115,000 to 129,000 bp
Low gene density in the larger eukaryotic genomes, is also due to the considerable amounts of repetitive DNA
Yeast contain very little repetitive DNA, although 30% of its genes are duplicated. In multicellular eukaryotes there are lots of repetitive DNA and in most cases, are directly related to genome size
Only about 10% of C. elegans contains repetitive DNA whereas in large genomes of mammals there are over 40% of repeat sequences. Most of these repeats are derived from transposable genetic elements (transposons)

7. Eukaryotic Genomes Cont….
Transposons are found in genomes of many organisms (bacteria, fungi, protozoa, plants and animals) and are structurally diverse. Transposons are mobile DNA sequences
Highly repetitive DNA is more abundant in larger genomes but there is no direct correlation between the amount of highly repetitive DNA and genome size.
Much of highly repetitive DNA in most species including humans, is present in the regions of chromosomes that flank the centromeres (centromeric heterochromatin) and in the telomeres
This DNA is difficult to sequence, most of the unsequenced DNA in human genome (472million bp) consist of highly repetitive sequences

8. Eukaryotic Genomes Cont….
Introns are more prevalent and longer in the large eukaryotic genome. Intergenic regions are also longer in the larger eukaryotic genomes.
The number of distinct protein domain encoded by genes does not vary much between genome sizes. Predicted number of proteins domains encoded by A. thaliana, D. melanogaster and human genomes are 1012, 1035, and 1262, respectively
Species
4,900
9,500
4,500
127,900
20,516
13,792
25,706
22,287
100,291,841
131,000,899
116,566,763
2,851,330’913
roundworm
Fruit fly
Mouse ear cress
Human
Nematode
Caemorhabditis elegans
Insects
Drosophila melanogaster
Plant
Arabidopsis thaliana
Vertebrates
Homo sapiens
Gene Density
(bp/gene)
Predicted number of genes
Genome Size in nucleotide pairs
Common Name
Table: Size of Selected Eukaryotic Genomes

9. Eukaryotic Genomes Cont….
Distantly related species have many genes in common, e.g. 18% of Arabidosis and 50% of Drosophila have human homologues
The proportion of homologous genes is even greater in closely related species. Furthermore, in closely related species, the entire chromosome often show a similar arrangement of genes

10. Introns Discovered in 1970s Different types of introns
Two hypotheses of origin
‘Introns early’
Ancient and gradually being lost from eukaryote genomes
‘Introns late’
evolved relatively recently and gradually accumalating in eukaryote genomes

11. Prevalence of Introns

12. Classification of introns
Self splicing

13. GU-AG Introns
‘introns early’
‘exon theory of genes’ – Gilbert 1987

14. Exon theory of genes

15. Introns early hypothesis
All genomes originally possessed introns
Bacterial genomes do not have GU-AG introns
Therefore must have been lost at an early stage
How? Without disrupting genes?
Not really feasible  introns late hypothesis

16. Introns late hypothesis
To begin with, genes had no introns
Introns developed in eukaryote genomes and proliferated
Group II introns and GU-AG introns similar in terms of splicing
Group II moved from organellar genomes to nuclear eukaryote genomes?
Or did GU-AG introns evolve from group II introns? – introns early hypothesis

17. Introns early hypothesis
Position of introns in homolgous genes from unrelated organisms should be similar since all descended from ancestral gene with introns
Initial evidence showed this was true

19. Later evidence (more lineages examined) its was shown that some introns were lost in some positions and gained in others
Introns must have moved by recombination events
Fits both hypotheses

20. Domain split
For introns early, introns should split domains of different proteins
Again, initial evidence supported this
But more globulin genes showed more than 10 introns- therefore no correlation between introns and junctions between domains
Domain duplication and shuffling

21. Domain duplication

22. Domain shuffling

23. Introns – early vs late
Subsequent gain and loss of introns over time in different lineages

24. References
Belshaw, R. and Bensasson, D. (2006) The rise and fall of introns. Heredity. 96: