Gene Duplication

1. Gene Duplication

2. Gene Duplication - History 1936: The first observation of a duplicated gene was in the Bar gene of Drosophila. 1950: Alpha and beta chains of hemoglobin are recognized to have been derived from gene duplication 1970: Ohno developed a theoretical framework of gene duplication 1995: Gene duplications are studied in fully sequenced genomes

3. Types of Genomic Duplications • Part of an exon or the entire exon is duplicated • Complete gene duplication • Partial chromosome duplication • Complete chromosome duplication • Polyploidy: full genome duplication

4. Mechanism of Gene Duplication Genes are duplicated mainly due to unequal crossing over

5. Mechanism of Gene Duplication If these regions are complementary, it increases the chance of unequal crossing over. For example, if both of these regions are the same repeated sequence (microsatellite, transposon, etc’…)

6. After a Gene is Duplicated • Alternative fates: • It can die and become a pseudogene. • It can retain its original function, thus allowing the organism to produce double the amount of the derived protein. • The two copies can diverge and each one will specialize in a different function. Divergence One copy dies Identical copies

7. Invariant repeats If the duplicated genes are identical or nearly identical, they are called invariant repeats. Many times the effect is an increase in the quantity of the derived protein, and this is why these duplications are also called “dose repetitions”. Classical examples are the genes encoding rRNAs and tRNAs needed for translation. Invariant repeats

8. Duplications of RNA-specifying genes

9. rRNA Ribosome is a complex of proteins and RNA (called rRNA) on which proteins are built, based on the information in the mRNA. Ribosomes are always composed of two units – big and small.

10. rRNA In prokaryotes the entire ribosome is 70S, and is composed of a 50S large subunit, and a 30S small subunit. In eukaryotes the entire ribosome is 80S, and is composed of a 60S large subunit and a 40S small subunit. The S value is the sedimentation coefficient in ultracentrifuge.

11. rRNA There are also ribosomal genes coded by the mitochondrial genome. In fact, the mitochondrial ribosome is coded by both nuclear and mitochondrial genes.

12. Correlation between the number of rRNA genes and the genome size Numbers of rRNA and tRNA genes per haploid genome in various organisms __________________________________________________________________________ Genome Source Number of Number of Approximate rRNA sets tRNA genesa genome size (bp) __________________________________________________________________________ Human mitochondrion 1 22 2  104 Nicotiana tabacum chloroplast 2 37 2  105 Escherichia coli 7 ~ 100 4  106 Neurospora crassa ~ 100 ~ 2,600 2  107 Saccharomyces cerevisiae ~ 140 ~ 360 5  107 Caenorhabditis elegans ~ 55 ~ 300 8  107 Tetrahymena thermophila 1 ~ 800c 2  108 Drosophila melanogaster 120-240 590-900 2  108 Physarum polycephalum 80-280 ~ 1,050 5  108 Euglena gracilis 800-1,000 ~ 740 2  109 Human ~ 300 ~ 1,300 3  109 Rattus norvegicus 150-170 ~ 6,500 3  109 Xenopus laevis 500-760 6,500-7,800 8  109 __________________________________________________________________________

13. Correlation between number of rRNA genes and genome size: an exception Numbers of rRNA and tRNA genes per haploid genome in various organisms __________________________________________________________________________ Genome Source Number of Approximate rRNA sets genome size (bp) __________________________________________________________________________ Human mitochondrion 1 2  104 Nicotiana tabacum chloroplast 2 2  105 Escherichia coli 7 4  106 Neurospora crassa ~ 100 2  107 Saccharomyces cerevisiae ~ 140 5  107 Caenorhabditis elegans ~ 55 8  107 Tetrahymena thermophila 1 2  108 Drosophila melanogaster 120-240 2  108 Physarum polycephalum 80-280 5  108 Euglena gracilis 800-1,000 2  109 Human ~ 300 3  109 Rattus norvegicus 150-170 3  109 Xenopus laevis 500-760 8  109 __________________________________________________________________________ The general pattern: bigger genomes  more genes to transcribed  more rRNA needed.

14. Variant repeats Some classic examples: Trypsin, the digestive enzyme and Thrombin (cleaves fibrinogen during blood clotting) were derived from a complete gene duplication. Lactalbumin, connected with lactose synthesis and Lysozyme, which degrades bacteria cell wall are also a result of an ancient gene duplication. Variant repeats

15. Vision. The Opsins stories

16. Cones and Rods There are two types of photoreceptor cells in the human retina, rods and cones.

17. Cones and Rods Rod cells are responsible for vision at low light levels (scotopic vision). They do not mediate color vision, and have a low spatial acuity

18. Cones and Rods Cone cells are active at higher light levels (photopic vision). They are capable of color vision and are responsible for high spatial acuity

19. Colors There are 3 types of pigments in cones. Their peaks of absorption are at about 430, 530, and 560 nanometers.

20. Colors The cones are “loosely” called "blue", "green", and "red“. “loosely” because: 1.the names refer to peak sensitivities (which in turn are related to the ability to absorb light) rather than to the way the pigments would appear if we were to look at them.

21. Colors The cones are “loosely” called "blue", "green", and "red“. “loosely” because: 2.Monochromatic lights whose wavelengths are 430, 530, and560 nanometers are not blue, green, and red but violet, blue-green, and yellow-green

22. Terminology Terminology is almost impossible to change.Some call the cones just long, middle, and short. An impossible elephant

23. Opsin and retinal Each photopigment consists of two parts: a protein called opsin and a lipid derivative called retinal. The opsin is a member of the superfamily of G-protein coupled receptors. The opsin’s sequence determines the absorbance

24. Opsin Genetics The blue opsin is encoded by an autosomal gene. The red and green opsins are encoded by X-linked genes. There are cases in which the green opsin is duplicated on the X chromosome. Red and green are very similar in amino-acid sequence (96%). Blue is more diverged (43%). Blue diverged about 500 mya (million years ago). Red and green diverged only 25-35 mya.

25. Opsin Genetics Indeed new-world monkeys have only one X-linked pigment, so the divergence of green and red occurred after the divergence of new-world monkeys from old-world monkeys. Thus, old-world monkeys are trichromatic.

26. Opsin Genetics New-world monkeys have only one X-linked locus (except for the howler monkey from the Alouatta genus). howler monkey

27. Opsin Genetics But the X-linked locus in the new world monkeys, such as for squirrel monkeys and tamarins, can be highly polymorphic, with some alleles similar to the red opsin and some to the green. Thus, a female can be trichromatic (if heterozygous) but males are always dichromatic. Dichromatic monkeys cannot distinguish between red and green. Squirrel monkeys

28. Ishihara Plates: are you color blind?

29. The individual with normal color vision will see the number 5 revealed in the dot pattern. An individual with Red/Green (the most common) color blindness will see the number 2 revealed in the dots 5 or 2?

30. Opsin: conclusion one Old world monkeys achieved trichomatic vision by a mechanism akin to isozymes (different proteins coded by different loci). Heterozygous female squirrel monkeys achieved trichomatic vision by using two “allozymes” (distinct proteins encoded by different allelic forms at a single locus). The polymorphism is probably a form of overdominant selection.

31. Opsin: selective advatage? The selective advantage of trichromatic vision is thought to be the ability to detect ripe fruits against a background of dense green foliage.

32. Ortholog, Paralog Mouse 1 Rat 1 is orthologous to Mouse 1 and to Mouse 2 Rat 2 is orthologous to Mouse 1 and to Mouse 2 Mouse 1 and Mouse 2 are paralogous Rat 1 and Rat 2 are paralogous Human 1 is orthologous to all other genes. Two independent duplications Mouse 2 Rat 1 Rat 2 Human 1

33. Ortholog, Paralog Mouse 1 Rat 1 is paralogous to Mouse 2 and to Rat 2 Mouse 1 is paralogous to Mouse 2 and to Rat 2 Mouse 1 and Rat 1 are orthologous Mouse 2 and Rat 2 are orthologous Human 1 is orthologous to all other genes. One duplications Rat 1 Mouse 2 Rat 2 Human 1

34. Ortholog, Paralog Mouse 1 Rat 1 Mouse 2 Rat 2 Human 1 Orthologous genes are usually more similar in terms of function than paralogous ones!

35. Organisms Have a Complicated Hierarchy Canis familiaris. Common name = Dog. The species = familiaris Genus = Canis. Family = Canidae. Order = Carnivora. Class = Mammalia. Phylum = Chordata. Kingdom = Metazoa [=Multi-cellular organism] First letter always in capital

36. Classified as Family Superfamily Genes Have a Much Simpler Classification If the sequence similarity is at least 50% it is of the same family. If it is less than 50% it is considered to be of the same superfamily.

37. The Globins The alpha globins are one family, the beta globins are another family. Alpha and beta globins, together with myoglobin are part of the globin superfamily. Another super family

38. Theory and Reality The strict 50% criterion is not always appropriate. Usually, other considerations such as function, tissue specificity and type of homology are also taken into account. Theory Reality