BIOL2007 CHROMOSOMAL EVOLUTION Genes are found on chromosomes. Rule:

1. BIOL2007 CHROMOSOMAL EVOLUTION Genes are found on chromosomes. Rule: Gene action usually independent of chromosomal location.

2. Exception 1: position effects. e.g. Hox gene clusters order reflects order of segments in the body that they control Suggests “cis-acting”, functional reasons Nonetheless, success in much genetic engineering implies that position often unimportant. Most genes “trans-acting”

3. Exception 2: Tight linkage and epistasis may also influence evolution. Or linkage disequilibrium. With epistasis or linkage disequilibrium, genes do not act independently. Epistasis usually not strong; except Papilio, HLA. Linkage disequilibria up to <1 Mb in humans, and <100 Kb in Drosophila Reich, D. et al. 2003. Nature411, 199 - 204 Humans: 3,400,000,000 bp per genome ½ of 1 mllnth = 160 kb

4. However, the fact that genes are on chromosomes influences evolution far beyond the minor effects of position effects and linkage disequilibria. Because the genes are arranged on long strings, and because chromosomes themselves act as genetic elements:- Holistic selective effects act on 100s to 1000s of genes at a time. WOW!!

5. Chromosomal rearrangements: gross changes in chromosomal morphology. Lots of Greek: telomere, centromere, autosome, chromosome, heterochromatin... Chromosomal morphology

6. Rearrangements

7. Chromosomal genotypes called karyotypes. • Karyotype often means number of chromosomes, for instance, "the human karyotype is 2n = 46". • Polyploidy. Common chromosomal mutation involving a doubling of numbers of copies: • autopolyploidy (doubling of endogenous chromosomes); • allopolyploidy (hybridisation  doubling) • Abnormal numbers – aneuploidy

8. Autopolyploidy and allopolyploidy popular in flowering plants • 30% of species are of polyploid origin • 2-3% of plant speciation assoc. with new polyploidy • Probably because monoecious and hermaphrodite plants can self  polyploid offspring with fully balanced gametes. • If tetraploidmates with diploid, the F1 is triploid; causes aneuploidy in the offspring, offspring almost invariably sterile. Duplications of some but not all genetic material • So polyploidy can lead to speciation

9. How do rearrangements occur? Chromosome breakage. Can occur via radiation, mutagens etc. Repeated sequences, especially transposable elements, in the DNA may frequently be involved, i.e. non-homologous recombination e.g. P- elements in Drosophila. Alu elements probably do in mammals; perhaps in us?

10. Breakage leads to "sticky ends" (? something to do with the function of a telomere?). Telomere – repeated motifs. Telomere's function: to "cap" sticky ends, prevents chromosomal mutation. Grows to replace losses in DNA synthesis – telomerase. Telomeric inversions are rare  Most (successful) rearrangements are reciprocal: paracentric or pericentric inversions; reciprocal translocations also preserve the telomere, and are common too.

11. Evolutionary effect of rearrangements General rule: Heterozygous rearrangements often lead to the production, in meiosis, of: UNBALANCED GAMETES (duplications and deletions in progeny)

12. e.g. Paracentric inversions Inversion heterozygotes; chromosomes pair in loops No crossing over in inversion: gametes fineCrossing over in inversion, problems

13. dicentric bridge(breaks at cell division) acentric fragment (lacks centromere, becomes lost) duplications and deletions of chromosomal material heterozygote disadvantage  fixation (except in many flies, where paracentric inversions act crossover suppressors)

14. Evolution of paracentric inversions Paracentric inversions in Diptera: No crossing over in male, so no damage to sperm. In female, dicentrics/acentrics go to polar bodies. So little or no damage to egg chromosomes. Paracentric inversions are commonly polymorphic in Diptera. There is even evidence for heterozygous ADvantage  maintains polymorphisms e.g. Drosophila, & Anopheles, malaria mosquitoes.

15. Pericentric inversions Like paracentric inversions, only worse. Reciprocal translocations Approximately 50% (or more) unbalanced gametes due to non-disjunction, or non- separation of homologous parts of chromosomes; duplications and deletions result Because pericentric inversion and translocation heterozygotes produces such unbalanced gametes, the rearrangements cause heterozygote disadvantage. usually fixed within populations; may differ between populations

16. Phylogeny from rearrangements Banding patterns; can identify chromosomes and chromosome parts. In humans/apes, chromosome banding patterns first showed that chimps are more closely related to humans than gorillas Humans differ from closest relatives by 9 pericentric inversions and 1 centric fusion

17. Humans and great apes 9 pericentric inversions, and one reciprocal translocaton from Yunis & Prakash (1982) Science 215, 1525-1530.

18. Evolutionary oddities about chromosomes • Poorly understood. • Chromosome number is variable. • In Drosophila melanogaster, 4 pairs of chromosomes (n = 4, 2n = 8). Of these, only 3 very active, X, 2 and 3. • In humans, 23 pairs (n = 23, 2n = 46). Mammals in general are highly variable in chromosome number. • Across the whole Lepidoptera, some variability (10-100s!), but strong modal number of n = 31.

19. "Karyotypic orthoselection" Similar repeated change in many chromosomes at once. Not fully explained. For example, the primitive chromosome number of chromosomes in Mus musculus domesticus, the house mouse, is 2n = 40, all acrocentrics. However, by a series of Robertsonian fusions, there are multiple chromosomal races with less, some of which have as few as 2n = 22. Nobody knows why!

20. What explains these patterns? • Not entirely clear. • Approx. 1 chiasma (causing a crossover) per chromosome arm • perhaps chromosome number is an adaptation (like sex) which affects overall recombination in the genome. • Many chromosomes • lots of of recombination (50% recombination between chromosomes, plus a lot of chiasmata).

21. Evolutionary significance Heterozygous disadvantage may prevent evolution of new chromosome rearrangements Most populations should be fixed. In general, true. But polymorphisms occur. e.g. Diptera. Often, non-disjunction rates low; e.g Mus. However, mostly some heterozygous disadvantage, leading to fixation Can cause a partial barrier between populations fixed for different rearrangements (e.g. species).

22. Chromosomal evolution and speciation Species: absence of hybrids, hybrid inviability, or sterility of hybrids Barriers between chromosome races therefore similar to barriers between species  chromosomes important in speciation? Controversial (MJD White, Guy Bush 1970s, "stasipatric speciation"). Chromosomal rearrangements certainly contribute to isolation: species often differ chromosomally. But generally doubted that drift important.

23. For example, humans 2n = 46, chimps 2n = 48 9 pericentric inversions + 1 centric fusion human-chimp hybrids would almost certainly be very infertile, due to chromosomal problems alone

24. Did chromosome change cause speciation? Or did it occur since separation? Most now think genic differences more important than chromosomes in speciation (except polyploidy). Recent suggestions: Rearrangements trap groups of genes effecting ecological differences? Due to suppression of recombination by rearrangement. e.g. in Drosophila pseudoobscura vs. D. persimilis

25. TAKE HOME POINTS • "Position effects" known, but often unimportant • But karyotypes: have strong holistic, selective effects • Chromosomal rearrangement heterozygotes: • reduced fertility, heterozygote disadvantage • Rearrangement polymorphisms usually rare, found in • hybrid zones between species or • chromosome races only • But, in some groups, chromosomal polymorphisms • common within species.

26. Species often differ in karyotype • Rearrangements contribute to hybrid sterility/inviability. But not much? • Rearrangements may prevent recombination • allowing distinct populations to arise, • maybe in initial stages of speciation • FURTHER READING • FUTUYMA, DJ 2005. Evolution Ch 8 pp. 181-185. • YUNIS & PRAKASH 1982. Science 215, 1525-1530. • (Human, chimpanzee, gorilla, orang-utan chromosomes)

27. Possible mechanism: “the shifting balance” today, considered somewhat controversial, but must explain some chromosomal evolution?

28. Translocations and Robertsonian rearrangements common in mammals. Usually, populations are fixed for a translocation. Populations fixed for alternative rearrangements often called chromosomal races. Common in species such as the european house mouse Mus musculus domesticus. Non-disjunction rates often low, 0% - 15%, not approx. 50% as one might expect. Mammals, like Drosophila, appear to have mechanisms which reduce production of unbalanced gametes.

29. A translocation polymorphism in humans One human chromosome involved in translocation polymorphism is chromosome 21; a heterozygote for this translocation can produce Down’s syndrome offspring.