1. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini GENOME EVOLUTION Questo documento è pubblicato sotto licenza Creative Commons Attribuzione – Non commerciale – Condividi allo stesso modo http://creativecommons.org/licenses/by-nc-sa/2.5/deed.it

2. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 1. Evolution of the eukaryotic nuclear genome T nuclear genome of eukaryotes is thought to have initially evolved as a mixture of archaeal genes (involved in information transfer) and eubacterial genes (involved in metabolism and other basic cellular functions). T nuclear genome of eukaryotes is thought to have initially evolved as a mixture of archaeal genes (involved in information transfer) and eubacterial genes (involved in metabolism and other basic cellular functions). As eukaryotes developed into complex multicellular organisms, the number of genes and size of the nuclear genome increased and various other properties were altered, notably the amount of repetitive DNA and the fraction of coding DNA. As eukaryotes developed into complex multicellular organisms, the number of genes and size of the nuclear genome increased and various other properties were altered, notably the amount of repetitive DNA and the fraction of coding DNA. The transition from the DNA of a typical simple eukaryotic cell precursor to the DNA of a mammalian cell is therefore thought to have involved a huge increase in the size of the genome and a sizeable increase in gene number and in the percentage of noncoding and repetitive DNA. The transition from the DNA of a typical simple eukaryotic cell precursor to the DNA of a mammalian cell is therefore thought to have involved a huge increase in the size of the genome and a sizeable increase in gene number and in the percentage of noncoding and repetitive DNA.

3. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 2. Ancient genome duplication events Genome duplication (tetraploidization) is an effective way of increasing genome size and is responsible for the extensive polyploidy of many flowering plants. It can occur naturally when there is a failure of cell division after DNA duplication, so that a cell has double the usual number of chromosomes. Genome duplication (tetraploidization) is an effective way of increasing genome size and is responsible for the extensive polyploidy of many flowering plants. It can occur naturally when there is a failure of cell division after DNA duplication, so that a cell has double the usual number of chromosomes. Human somatic cells are normally diploid. However, if there is a failure of the first zygotic cell division, constitutional tetraploidy can result. Tetraploidy and other forms of polyploidy can be harmful and is often selected against. Human somatic cells are normally diploid. However, if there is a failure of the first zygotic cell division, constitutional tetraploidy can result. Tetraploidy and other forms of polyploidy can be harmful and is often selected against. However, whole genome duplication via polyploidy has undoubtedly occurred relatively recently in maize, yeast, Xenopus and some types of fish. It is likely therefore that genome duplication occurred several times in the evolution of all eukaryotic lineages, including our own. However, whole genome duplication via polyploidy has undoubtedly occurred relatively recently in maize, yeast, Xenopus and some types of fish. It is likely therefore that genome duplication occurred several times in the evolution of all eukaryotic lineages, including our own.

4. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 3. Whole-genome duplications Whole-genome duplications offer particularly dramatic examples of the duplication- divergence cycle. A whole-genome duplication can occur quite simply: all that is required is one round of genome replication in a germline cell lineage without a corresponding cell division. Whole-genome duplications offer particularly dramatic examples of the duplication- divergence cycle. A whole-genome duplication can occur quite simply: all that is required is one round of genome replication in a germline cell lineage without a corresponding cell division. Initially, the chromosome number simply doubles. Such abrupt increases in the ploidy of an organism are common, particularly in fungi and plants. After a whole-genome duplication, all genes exist as duplicate copies. However, unless the duplication event occurred so recently that there has been little time for subsequent alterations in genome structure, the results of a series of segmental duplications—occurring at different times—are very hard to distinguish from the end product of a whole-genome duplication. Initially, the chromosome number simply doubles. Such abrupt increases in the ploidy of an organism are common, particularly in fungi and plants. After a whole-genome duplication, all genes exist as duplicate copies. However, unless the duplication event occurred so recently that there has been little time for subsequent alterations in genome structure, the results of a series of segmental duplications—occurring at different times—are very hard to distinguish from the end product of a whole-genome duplication. In the case of mammals, for example, the role of whole genome duplications versus a series of piecemeal duplications of DNA segments is quite uncertain. Nevertheless, it is clear that a great deal of gene duplication has ocurred in the distant past. In the case of mammals, for example, the role of whole genome duplications versus a series of piecemeal duplications of DNA segments is quite uncertain. Nevertheless, it is clear that a great deal of gene duplication has ocurred in the distant past.

5. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 4. From diploidy to tetraploidy Following genome duplication, an initially diploid cell could have undergone a transient tetraploid state; subsequent large-scale chromosome inversions and translocations, etc., could result in chromosome divergence and restore diploidy, but now with twice the number of chromosomes Following genome duplication, an initially diploid cell could have undergone a transient tetraploid state; subsequent large-scale chromosome inversions and translocations, etc., could result in chromosome divergence and restore diploidy, but now with twice the number of chromosomes Following duplication of a diploid genome, each pair of homologous chromosomes (e.g. chromosome 1) is now present as a pair of identical pairs. The resulting tetraploid state, however, can be restored to diploidy by chromosome divergence, e.g. by an interstitial deletion (upper panel, a), a terminal deletion (lower panel, c) or by an inversion (b)

6. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 5. Polyploidization in plants In plants, new genes can be acquired by polyploidization. Allopolyploidy, which results from interbreeding between two different species, is also common and, like autopolyploidy, can result in a viable hybrid. Usually, the two species that form the allopolyploid are closely related and have many genes in common, but each parent will possess a few novel genes or at least distinctive alleles of shared genes. In plants, new genes can be acquired by polyploidization. Allopolyploidy, which results from interbreeding between two different species, is also common and, like autopolyploidy, can result in a viable hybrid. Usually, the two species that form the allopolyploid are closely related and have many genes in common, but each parent will possess a few novel genes or at least distinctive alleles of shared genes. For example, the bread wheat, Triticum aestivum, is a hexaploid that arose by allopolyploidization between cultivated emmer wheat, T. turgidum, which is a tetraploid, and a diploid wild grass, Aegilops squarrosa. The wild-grass nucleus contained novel alleles for the high- molecular-weight glutenin genes which, when combined with the glutenin alleles already present in emmer wheat, resulted in the superior properties for breadmaking displayed by the hexaploid wheats. Allopolyploidization can therefore be looked upon as a combination of genome duplication and interspecies gene transfer. For example, the bread wheat, Triticum aestivum, is a hexaploid that arose by allopolyploidization between cultivated emmer wheat, T. turgidum, which is a tetraploid, and a diploid wild grass, Aegilops squarrosa. The wild-grass nucleus contained novel alleles for the high- molecular-weight glutenin genes which, when combined with the glutenin alleles already present in emmer wheat, resulted in the superior properties for breadmaking displayed by the hexaploid wheats. Allopolyploidization can therefore be looked upon as a combination of genome duplication and interspecies gene transfer.

7. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 6. Evolution of the genus Triticum The evolution of bread wheat is a classic example of sympatric speciation through allopolyploidy. Modern wheat (Triticum aestivum) is a hexaploid represented by AABBDD (Figure 3.12). Its lineage can be traced to the tetraploid wheat Triticum dicoccum with an AABB genome that is produced by the intergeneric cross between the diploid wheat Triticum monococcum (AA) and goat grass Aegilops speltoides (BB). Later, a second intergeneric cross between T. dicoccum and Aegilops squarrosa, the latter contributing the D genome, occurred to produce modern bread wheat.

8. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 7. Genome duplication in yeast By analysis of the locations of duplicated genes, it was proposed in 1997 that the entire genome of S. cerevisiae became duplicated at some point in its evolutionary past and subsequently sustained rearrangements and gene loss. By analysis of the locations of duplicated genes, it was proposed in 1997 that the entire genome of S. cerevisiae became duplicated at some point in its evolutionary past and subsequently sustained rearrangements and gene loss. A recent analysis of gene order information from 14 hemiascomycetes, has confirmed the hypothesis that S. cerevisiae is a degenerate polyploid. Using gene order information alone, 70% of the S. cerevisiae genome were mapped into "sister" regions that tiled together with almost no overlap. Combining gene order and gene duplication data assigns essentially the whole genome into sister regions. A recent analysis of gene order information from 14 hemiascomycetes, has confirmed the hypothesis that S. cerevisiae is a degenerate polyploid. Using gene order information alone, 70% of the S. cerevisiae genome were mapped into "sister" regions that tiled together with almost no overlap. Combining gene order and gene duplication data assigns essentially the whole genome into sister regions. The 16 centromere regions of S. cerevisiae form eight pairs, indicating that an ancestor with eight chromosomes underwent complete doubling. Gene arrangements in Kluyveromyces lactis and four other species agree quantitatively with what would be expected if they diverged from S. cerevisiae before its polyploidization. In contrast, Saccharomyces exiguus, Saccharomyces servazzii, and Candida glabrata show higher levels of gene adjacency conservation, and more cases of imperfect conservation, suggesting that they split from the S. cerevisiae lineage after polyploidization. The 16 centromere regions of S. cerevisiae form eight pairs, indicating that an ancestor with eight chromosomes underwent complete doubling. Gene arrangements in Kluyveromyces lactis and four other species agree quantitatively with what would be expected if they diverged from S. cerevisiae before its polyploidization. In contrast, Saccharomyces exiguus, Saccharomyces servazzii, and Candida glabrata show higher levels of gene adjacency conservation, and more cases of imperfect conservation, suggesting that they split from the S. cerevisiae lineage after polyploidization.

9. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 8. S. cerevisiae is a paleoploid Wolfe K.H. and Shields D.C. Nature (1997) 387 708-713 ~100 million years ago, two ancestral diploid yeast cells each containing about 5000 genes fused to form a tetraploid.~100 million years ago, two ancestral diploid yeast cells each containing about 5000 genes fused to form a tetraploid. The species then became diploid (decay of sequence identity) and most (85%) of the duplicate copies were deleted.The species then became diploid (decay of sequence identity) and most (85%) of the duplicate copies were deleted. Current species with a haploid diploid life cycle and 5,800 genes that include many duplicates.Current species with a haploid diploid life cycle and 5,800 genes that include many duplicates.

10. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 9. Genome duplication events during vertebrate evolution In the case of vertebrates, two rounds of genome duplication have been envisaged at an early stage of vertebrate evolution. In the case of vertebrates, two rounds of genome duplication have been envisaged at an early stage of vertebrate evolution. Gene numbers in different species have been taken to provide some evidence for two rounds of tetraploidization in vertebrates: invertebrates such as C. elegans, Drosophila and the sea squirt Ciona intestinalis are estimated to have about 15 000–20 000 genes, about one quarter that expected in mammalian genomes. In addition, many single-copy Drosophila genes have four vertebrate homologues and certain gene clusters appear to have been quadruplicated Gene numbers in different species have been taken to provide some evidence for two rounds of tetraploidization in vertebrates: invertebrates such as C. elegans, Drosophila and the sea squirt Ciona intestinalis are estimated to have about 15 000–20 000 genes, about one quarter that expected in mammalian genomes. In addition, many single-copy Drosophila genes have four vertebrate homologues and certain gene clusters appear to have been quadruplicated

11. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 10. Ancient genome duplications are not obvious If ancient tetraploidization events were rare in the evolution of the vertebrate genome, much intragenomic DNA shuffling would have occurred since the last such event. This means that the original evidence for tetraploidization events would be very largely obscured by subsequent chromosomal inversions, translocations, etc. If ancient tetraploidization events were rare in the evolution of the vertebrate genome, much intragenomic DNA shuffling would have occurred since the last such event. This means that the original evidence for tetraploidization events would be very largely obscured by subsequent chromosomal inversions, translocations, etc. Additionally, traces of gene duplication following genome duplication are likely to be frequently reduced by silencing of one member of each duplicated gene pair which then degenerates into a pseudogene. After hundreds of millions of years without any function, the nonprocessed pseudogenes generated following the last proposed genome duplication would have diverged so much in sequence as to be not recognizably related to the functional gene, even assuming they have not been lost during occasional rearrangements leading to gene deletion. Additionally, traces of gene duplication following genome duplication are likely to be frequently reduced by silencing of one member of each duplicated gene pair which then degenerates into a pseudogene. After hundreds of millions of years without any function, the nonprocessed pseudogenes generated following the last proposed genome duplication would have diverged so much in sequence as to be not recognizably related to the functional gene, even assuming they have not been lost during occasional rearrangements leading to gene deletion.

12. Genetica per Scienze Naturali a.a. 08-09 prof S. Presciuttini 11. Long term consequences of genome duplications Pattern Predicted for the Relative Locations of Paralogous Genes from Two Genome Duplications Pattern Predicted for the Relative Locations of Paralogous Genes from Two Genome Duplications (A) Representation of a hypothetical genome that has 22 genes shown as colored squares. (B) A genome duplication generates a complete set of paralogs in identical order. (C) Many paralogous genes suffer disabling mutations, become pseudogenes, and are then lost. (D) A second genome duplication recreates another set of paralogs in identical order, with multigene families that retained two copies now present in four, and those that had lost a member now present in two copies. (E) Again, many paralogous genes suffer disabling mutations, become pseudogenes, and are then lost. This leaves only a few four-member gene families, but the patterns of 2- and 3-fold gene families reveals that the sequential duplications had been of very large regions.