1. Sex determination CfE Advanced Higher Biology Unit 2: Organisms and Evolution

2. 2biii – Sex determination 1.Gender (2) 2.Chromosomal sex determination (2) 3.Sex linkage (5) 4.Dosage compensation (2) 5.Environmental sex determination (3) 6.Changing sex (2) Contents and number of slides for each topic

3. SQA mandatory key information Sex determination in mammals and Drosophila, sex ratio and resource availability. Environmental factors can affect sex determination. Change of sex through size, competition or parasitic infection. Hermaphrodites. Sex linked patterns of inheritance in carrier females and affected males in terms of gene products. Random inactivation on X chromosomes in females prevents a double dose of gene products. Half of the cells in any tissue will have a working copy of the gene in question therefore carriers remain unaffected by any deleterious mutations.

4. Key concepts 1 Many species are hermaphroditic. For some species environmental rather than genetic factors determine sex. Environmental sex determination in reptiles controlled by environmental temperature of egg incubation. Sex chromosomes, such as XY in live-bearing mammals and some insects including Drosophila. In many of the mammals a gene on the Y chromosome determines development of maleness. In some species the sex ratio of offspring can be adjusted in response to resource availability.

5. Key concepts 2 In live-bearing mammals, the heterogametic (XY) male lacks homologous alleles on the smaller (Y) chromosome. This can result in sex-linked patterns of inheritance as seen with carrier females (XBXb) and affected males (XbY). In the females, the portions of the X chromosome that are lacking on the Y chromosome are randomly inactivated in one of the homologous X chromosomes in each cell. This effect prevents a double-dose of gene products. Carriers remain unaffected by any deleterious mutations on these X chromosomes as the X-chromosome inactivation is random, half of the cells in any tissue will have a working copy of the gene in question.

6. Gender Males and females Many animals have separate genders. In some animal species the males and females are very similar. Other animal species show sexual dimorphism. Some plants are unisexual and have male and female plants. For example, only female hollies can produce berries. Male holly flower Female holly flower Swans: Ralfie / Wikimedia, Ducks: Keven Law / Wikimedia, Holly flowers: Tigerente / Wikimedia

7. Gender Hermaphrodites In Greek mythology, Hermaphroditus was the child of Hermes and Aphrodite and had both male and female characteristics. Some animals and plants have male and female organs in one individual. Reproductive structures in many flowers mature at different times to prevent self-pollination. Earthworms and most land molluscs are hermaphroditic but must meet another individual to reproduce. https://www.youtube.com/watch?v=4eNz3 Si6uhc https://www.youtube.com /watch?v=2fG-KkR3FZ8

8. Chromosomal sex determination X and Y in humans Karyotypes developed in early 20 th Century and it took until 1956 to agree on 46 chromosomes for humans. By 1959, agreed on 44 autosomes and two sex chromosomes in humans: – Females have two large sex chromosomes, both called X – Males have an X and a small Y chromosome. Live-bearing mammals have this system - all mammals except Platypus and Echidna. Drosophila melanogaster also has this system with 6 autosomes and two sex chromosomes, X and Y (this is unusual for insects).

9. Chromosomal sex determination SRY gene Default setting for human embryonic development is to become female (hence male nipples!). Y-chromosome has a gene called SRY (Sex determining Region of Y-chromosome). SRY controls the development of male genitalia and male characteristics. SRY is a ‘master switch’ which produces a transcription factor to switch on other genes. Many of these genes are on the autosomes but are only transcribed in males due to SRY control. XX male due to SRY translocated to X-chromosome. XY female due to SRY deleted from Y-chromosome.

10. Task In pairs - Produce a 3 slide powerpoint -on either: Klinefelter’s Syndrome Swyer Syndrome XX Male Syndrome Androgen insensitivity syndrome The Olympics and Androgen Insensitivity Syndrome The link between SRY and dopamine-related diseases. You must relate the power- point to the involvement of the SRY gene. Pictures, video-clips, real- life examples!!!

11. Sex linkage X and Y are homologous chromosomes X and Y are an exception to the homology definition. Human X-chromosome is larger than Y and has about 2000 genes compared to about 450. X and Y are homologous because they pair up during meiosis I. Pairing is due to a small area of homology around the centromere. The Y-chromosome lacks many genes found on its homologous X-chromosome. This leads to a pattern of inheritance called sex linkage. In XX females, a recessive allele on one X can be masked by a dominant allele on the other X. In XY males, a recessive allele on the X has no second copy to mask its effects.

12. Sex linkage Homogametic and heterogametic Human females produce all gametes with the same combination of chromosomes = homogametic. Human males produce gametes with two possible combinations of chromosomes = heterogametic. Because they are homologous, the sex chromosomes are separated during meiosis into different gametes. 44 + XX 22 + X 44 + XY 22 + Y

13. Sex linkage White-eyed males In the early 1900s, T. H. Morgan studied inheritance in Drosophila melanogaster to try to disprove Mendel’s theory of the 3:1 ratio It took two years to find any variation in his vast fly breeding programme. Eventually a male fly was found which had white eyes. (His wife found it.) This white-eyed male was crossed with a normal red-eyed female. We will use the notation X R to show the red eye allele is on the X-chromosome and is dominant to white eye, X r. XrYXrY XRXRXRXR XRXR XrXr XRXrXRXr YXRYXRY

14. Sex linkage Carrier females All the flies in the F 1 had red eyes. Flies with genotype X R X r are carrier females. Morgan crossed the F 1 with each other. F 2 came out with a 3:1 ratio of red-eyed flies to white-eyed flies. But all the white-eyed flies were males. Which flies could be crossed to get white-eyed females? XRYXRYXRXrXRXr XRXR XrXr XRXR X R Red-eyed female X R X r Red-eyed carrier female Y X R Y Red-eyed male X r Y White-eyed male

15. Sex determination in Drosophilla WATCH: https://www.youtube.com/watch?v=NQ4MhCU15E 15:43 minute video explaining sex determination in Drosophila.

16. Sex linkage Human examples Even though the mechanism of inheritance was not understood, examples of sex linkage had already been noticed in humans before Morgan found the white-eyed fly in 1910. Red-green colour blindness, 1798 Haemophilia, 1803 Duchenne muscular dystrophy, 1834 Other examples have been noticed since then, such as Vitamin D resistant rickets (1937), which is unusual in being a dominant allele. Research – each of these disorders http://www.s-cool.co.uk/a- level/biology/genetics/test-it/exam-style- questions

17. Dosage compensation X-chromosome inactivation Males are heterogametic (with only one X-chromosome) while females are homogametic (two X-chromosomes). Despite this, female cells do not have a double-dose of gene products from their X-chromosomes. In females, one X-chromosome is partially inactivated early in embryonic development. The regions inactivated are those that are lacking on Y-chromosome. (Deacetylation of histones, methylation of bases.) The inactivated X-chromosome shows up as a highly condensed region on the inside of the nuclear membrane – a Barr body. Xi = Barr body (inactivated X) Steffen Dietzel / Wikimedia

18. Dosage compensation Mosaics Cats show this mosaic in their fur as a coat colour gene is found on the X-chromosome. The two alleles are black and ginger and tortoiseshell cats are females, X B X G. Because of random X-inactivation, an XX female is a mosaic of cells with different X-chromosomes active and inactive. A carrier of a deleterious alleles (e.g. X D X d ) remains unaffected because she still has a working copy of the gene in half of the cells in every tissue. Suziecat / Wikimedia

19. Ginger Cats If you see a ginger cat, why is it more likely that it is male than female?

20. Environmental sex determination Temperature affects sex ratio in reptiles In turtles and crocodiles, the level of expression of some genes is affected the temperature during a sensitive period in development. For some reptiles, there is trend in the effect of temperature on the sex ratio. – In Hermann’s Tortoises, below 31  C is all males and above 32  C is all females. In other reptiles, the extremes cause the production of one sex while the intermediate temperature produces the other sex. – In Mississippi Alligators, males only develop at 32–34  C while females are produced at temperatures below 32  C and above 34  C.

21. Environmental sex determination Parasites can affect sex ratio In some arthropods, particularly insects, sex ratio is affected by infection by bacteria of the genus Wolbachia. Some species having chromosomal sex determination but the bacteria kill the males or feminize them. Other insects rely on infection by Wolbachia to cause their sex determination! Research reported in 2007 showed that human mothers infected by the protist, Toxoplasma gondii, have a higher proportion of male offspring. This parasite may also affect human behaviour. Transmission electron microscope image of Wolbachia bacteria inside an insect cell

22. Research – effect of Toxoplasma gondii and human reproduction and behaviour Try analysing this paper as you did for unit 3 NAB - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC25261 42/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC25261 42/ Could there be a link to this and SRY gene? Why?

23. Environmental sex determination Competition affects sex ratio Some species can actively change the sex ratio of their offspring. When a solitary female Lesser Mouse Lemur detects the urine of other females in her habitat she switches from producing one-third males to two-thirds males. Male offspring disperse away from the home range sooner than female offspring so this reduces competition. Female Seychelles Warblers in a high quality territory produce 87% females but in a poor territory they produce 77% males. Female offspring stay and help raise the next brood with their mother while males disperse away and reduce competition. Gabriella Skollar & Rebecca Lewis / Wikimedia

24. Changing sex Group-living fish Clown fish live in groups with a large dominant female and a number of smaller males. – If the female is removed, the largest male becomes female. Bluehead wrasse have one male with a group of females. – Removal of the male causes the largest female to grow twice its size and change its colouration. This sex change is influenced by aromatase, an enzyme that controls the androgen:oestrogen ratio.

25. Changing sex Size and parasites The sea anemone Metridium senile changes from male to female as it gets larger. – Bigger females may be necessary due to the higher investment by females in producing gametes for reproduction. A nematode (Gasteromermis sp.) parasitises the aquatic larvae of a type of mayfly, Baetis bicaudatus. – Females become sterile. Some parasitised males become ‘intersex’ while others become completely female. – All the parasitised animals (males and females) behave like females when adult and crawl into the water as if to lay eggs. – This helps the parasite return to infect the next generation. Stan Shebs / Wikimedia

26. Research – the genetic basis of ‘sex change’ animals! What’s the genetic basis?