4 4 1 SEX CHROMOSOMES AND SEX DETERMINATION Sex chromosomes and Sex Determination Sex chromosomes If present sex chromosomes may not have the same size shape or genetic potential In humans females have 2 so called X chromosomes and males have one X chromosome and one Y chromosome The human X and Y not strictly homologous Y is much smaller and lacks most of loci contained on the X They do behave as homologs during meiosis however Soon after the rediscovery of Mendel s work experiments with Drosophila produced results in which the phenotypic proportions differed between males and females These results were explained by postulating that the genes were located on the X chromosome of Drosophila which is present in two copies in females but only one copy in males Mammals birds some insects and a few plants have this kind of sex chromosome system One sex has a pair homologous chromosomes whereas the other sex has one chromosome that resembles the homologous pair and one different chromosome Mammals and Drosophila females have two X chromosomes males have one X chromosome and one Y XX XY These are the sex chromosomes all other chromosomes are called autosomes The sex with two different chromosomes is the heterogametic sex The other is the homogametic sex For the X chromosome then female mammals and Drosophila have two copies of each gene on the X but males have only one Females can be homozygous or heterozygous but males are hemizygous Birds and Lepidoptera Moths and Butterflies have the opposite pattern Males are homogametic ZZ and females are heterogametic ZW 4 2 The Mammalian X Chromosome The X chromosome carries hundreds of genes but few if any of these have anything to do directly with sex However the inheritance of these genes follows special rules These arise because males have only a single X chromosome almost all the genes on the X have no counterpart on the Y thus any gene on the X even if recessive in females will be expressed in males Genes inherited in this fashion are described as sex linked or more precisely X linked X Linkage An Example Hemophilia A is a blood clotting disorder caused by a mutant gene encoding the clotting factor VIII This gene is located on the X chromosome With only a single X chromosome males who inherit the defective gene always from their mother will be unable to produce factor VIII 1 and suffer from difficult to control episodes of bleeding In heterozygous females the unmutated copy of the gene will provide all the factor VIII they need Heterozygous females are called carriers because although they show no symptoms they pass the gene on to approximately half their sons who develop the disease and half their daughters who also become carriers X Y X XX XY Xh XhX XhY Women rarely suffer from hemophilia A because to do so they would have to inherit a defective gene from their father as well as their mother Until recently few hemophiliacs ever became fathers 4 3 The Mammalian Y Chromosome In making sperm by meiosis the X and Y chromosomes must separate in Meiosis I just as homologous autosomes do if you don t remember what happens in Meiosis I vs Meiosis II this would be a good time to review You will need to know this in order to understand much fo the remainder of this course This occurs without a problem because like homologous autosomes the X and Y chromosome synapse during prophase of meiosis I There is a small region of homology shared by the X and Y chromosome and synapsis occurs at that region Crossing over between the X and the Y occurs in two regions of pairing called the pseudoautosomal regions These are located at opposite ends of the chromosome The Pseudoautosomal Regions The pseudoautosomal regions get their name because any genes located within them so far only 9 have been found are inherited just like any autosomal genes Males have two copies of these genes one in the pseudoautosomal region of their Y the other in the corresponding portion of their X chromosome So males can inherit an allele originally present on the X chromosome of their father and females can inherit an allele originally present on the Y chromosome of their father This diagram shows the structure of the human Y chromosome Genes outside the pseudoautosomal regions Although 95 of the Y chromosome lies between the pseudoautosomal regions fewer than 80 genes have been found here Some of these encode proteins used by all cells and both sexes The others encode proteins that appear to function only in the testes A key player in this latter group is SRY 2 4 4 SRY and Mammalian Sex Determination It is often stated that sex determination in humans is based on the presence or absence of the Y chromosome However the situation is more complex Sex determination in humans and other mammals is actually due to a single gene that is normally located on the Y chromosome Near one of the pseudoautosomal regions but not in it is the SRY sexdetermining region The SRY produces a gene product TDF testis determining factor that triggers undifferentiated gonadal tissue in embryos to form testes SRY has been found in all mammals investigated The gene functions early in the developmental program that ultimately causes tissue that is developing into ovaries to switch their developmental so that they develop as testes Individuals without this gene develop as females Sometimes the SRY gene becomes associated with a chromosome other than the Y In these cases an individual can have the chromosome complement XY and be a perfectly normal female or be XX and be a normal male Beyond the XY pairing region and the TDF the Y contains very few genes SRY is a gene located on the short p arm just outside the pseudoautosomal region It is the master switch that triggers the events that converts the embryo from it s defaul developmental pattern as a female into a developmental sequence that results in a male If this gene is absent or inactivated a mammal develops into a female even if the Y chromosome itself is present Therefore it is not the Y chromosome that determines maleness or the presence of two X chromosomes that determines femaleness it is the presences or absence of the protein coded for by the SRY gene that determines gender in mammals What is the evidence On very rare occasions aneuploid humans are born with such karyotypes as XXY XXXY and even XXXXY Despite their extra X chromosomes all these cases are male This image courtesy of Robin Lovell Badge from Nature 351 117 1991 shows two mice with an XX