BSCI222 – Lecture 9 (missed Lecture 8) (10/3/13)- Second lecture on Mendellian genetics; missed the first one.- Chapter 4: Sex determination and sex-linked characteristics- Drosophila are the model system for studying sex genetics.o Small genome, easy to culture, short generation time, large chromosomes.o Salivary gland has many replications/copies of DNA without cell division of the centromere; called polytene chromosomes.o First experiments: collected mutants, looking for genetic traits. White eye mutant (wild type has red); did cross between white eyed male and wild type female, found that F1 all had red eyes, so red is dominant to white. Intercrossing F1 to make F2, get several flies with white eyes; BUT, all the females had red eyes, and some of the males had white, thus not a standard recessive trait. It’s a sex-linked trait. Autosomal recessive? Have to do reciprocal crosses (doing it the other way): red female with white male -> get red eyed F1, white female with red male -> red eyed female, white eyed males. The males of the second pairing are hemizygous, the Y chromosome doesn’t have a copy of the gene, so since the X from mom was ^w, they had to be white eyed; the females got an X^w from the mom but got a normal X^+ from the dad (because he’s red-eyed).  Two red-eyed parents (from red female and white male), gave red females and some white males; white female with red male -> half white and half red, across both sexes. Clues that it’s sex linked: reciprocal crosses don’t give you the same results, and different phenotypic ratios in the two sexes.  Hemizygous = only have one copy of the gene. BUT, when they crossed homozygous white female with red male -> saw some white females, even though should have had all red females and all white males. Hypothesized that the females were XXY, causing a nondisjunction, which is when 2 copies of the X chromosome in one gamete and a Y in the other gamete, or XY in one gamete and X in the other. The homozygous female is already rare, difficult to make, and has this problem, causing a bigger Punnet square. Eight possible children; YY and X+XwXw will die. - Nondisjunction: happens when meiosis goes wrong, and both homologs wind up in the same daughter cell. Can end up with an XX gamete and an O gamete (blank), or in a malecan have an XY gamete and an O gamete.o Happens in Meiosis I, because that’s where homologs separate (MII, sister chromatids are what is separating).o To determine sex in drosophila, compare ratio of X chromosomes to Autosomes. XX females have 1.0; XY males have 0.5. In humans it’s Y that determines sex, but in Drosophila it’s the X:A ratio. An XO fly’s ratio is 0.5 and is male, even though doesn’t have a Y chromosome. An XXY fly’s ratio is 1.0, will be female.- XX and XY is used for sex determination in all mammals.o Birds are different. The females are heterogametic, not the males. o Females are WZ (or ZW), males are ZZ. o Peacock locus: Ca+ (wild type) is blue (capital letter indicates its dominant), ca (recessive) is brown. Sex linked Show via recessive cross: blue female (Z^Ca+ W) and cameo male (Z^ca Z^ca) or cameo female (Z^ca W) with blue male (Z^Ca+ Z^Ca+).- Get blue males and cameo females; get all blue progeny. Intercrossfirst one, get half blue half brown across; intercross second, get blue males, half cameo females half blue. - Human sex chromosomes: o A Y chromosome originated from the X chromosome; genes were gradually lost until the chromosome became much smaller.o Still pairs with the X chromosome during meiosis, only at the tips (called pseudoautosomal regions, undergoing recombination just in those small regions). In the female, the X chromosomes are recombining the whole time; the males justget the small amount at the tips. o SRY gene, of Sox family, derived by duplication of a gene that’s found on the X chromosome called Sox3. Is found in the non-recombining region of the Y chromosome, never on the X.o A small amount of Y is recently X-transposed, a lot of it is X-degenerate, and then lots of it is ampliconic where they group together highly repetitive units. 60% of the region shows over 99.9% similarity.o Because the Y has lost so many genes, so have sex-linked inheritance, because recessive alleles are exposed when they’re the only copy.- Evolution of X inactivation:o Having the ratios of gene expression the same between all the different genes in the genome is pretty critical for development.o Can have more expression of one gene than another, as long as the ratio remains constant.o The big X chromosome (has about a thousand genes) has gradually lost genes on the Y; the Y only has 78 or 79 active genes. When the pairs started out millions ofyears ago, as an autosomal pair, they both had equal amounts of genes. Became sex chromosome, Y started to lose genes, ratio went wild.o There starts to be selection for the males to coax more expression from the genes on the X chromosome, creating a problem for females, because when you start increasing expression (accumulating mutations) -> starts expressing too much in the females. Conflict between preferred expression levels between males and females. New mechanism to balance it evolved; females developed a mechanism to silence many of the genes on the second X chromosome (essentially turn one oftheir X’s off, called X inactivation). One copy of the X will be all balled up into inactive chromatin, unable to express anything (called a Barr body, after the scientist who discovered them). o There are some genes that become expressed because of the X inactivation, because it makes the female essentially hemizygous, and now recessive alleles on the active X chromosome will be revealed. (absence of sweat glands in females)o Tortoiseshell cat fur: some orange, some black. Gives you some idea of when the X went inactive; patches derived from one particular cell in the embryo that continued to divide. o Nondisjunction happens in humans too: Turner Syndrome (XO, only 45 chromosomes) and Klinefelter Syndrome (XXY, 47 chromosomes) (could be nondisjunction in either male or female parent). Even with extra X’s, only one will be expressed, others become Barr bodies.- Sex and gendero Athleteso Androgen Insensitivity Syndrome (XY, insensitive to androgens, phenotypically female)- Sex determination in other species:o Hymenoptera (bees, wasps, and ants): ploidy level (whether they’re haploid (bee drones, males)