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Lecture 14

BIOC15Fall2013 Lecture 14 Notes and Lecture 15 Notes.docx

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Biological Sciences
Karen Williams

BIOC15Fall2013 Lecture 14 Notes: Genetics of Development and Lecture 15 Notes: Development of body plan Mitotic recombination on X chromosome o Female fruit fly  y sn / y sn o Mosaic animals have cuticles with the singed patches adjacent with bristle patches that are normal but with yellow cuticle o o this occurs during mitosis and has to do with the position of genes in relation to one another on the X chromosome o o o In a y sn / y sn Drosophila female, a mitotic crossover between the centromere and sn can produce two daughter cells, one homozygous for y and the other homozygous for sn, that can develop into adjacent aberrant patches (twin spots). This outcome depends on a particular distribution of chromatids at anaphase (top). If the chromatids are arranged in the equally likely opposite orientation, only phenotypically normal cells will result (bottom). o (b)Crossovers between sn and y can generate single yellow patches. However, a single mitotic crossover in these females cannot produce a single singed spot if the sn gene is closer to the centromere than the y gene. How do sex chromosomes relate to the sex of the organism? o Example: in humans the presence of a Y chromosome determines between male and female o In fruit flies the number of X chromosomes in comparison to autosomes determines sex o In bees  females are diploid and males are haploid o So how could you explain a genetically XX male?  the SRY gene (this gene dictates the development of testis, which then start to secrete testosterone, so it is the sex determining gene in mammals and marsupials) from the Y chromosome is translocated to the X chromosome in the father and passed on to the child  the child will have one X from the mother which is normal and one X from the father which contains the SRY gene and therefore will result in the individual developing as a male Sex-specific traits in Drosophila o 1 o some mutations affect the two sexes differently: o o ** = dominant mutation of sex lethal gene and * is recessive mutation of sex lethal gene How is sex determined in Drosophila? o o the tra gene has 3 exons and 2 introns o during RNA processing in females SXL (an RNA splicing regulator) causes the stop codon containing intron to be spliced out and so all three exons are present in females o in males, there is no SXL and the intron containing the stop codon is not spliced out so translation stops before exon 2, so there is no functional protein produced The X:A ratio regulates the transcription of the Sxl gene o several HLH transcription factors are key regulators in sex determination o Xlinked gens are numerator elements o Autosomal genes are ‘denominator elements’ o Numerator/denominator determines ratio of HLH homodimers and heterodimers o Only the homodimer activates the transcritption of Sxl  numerator dimers activate the transcription of this gene o 2 o Numerator elements are produced by the X chromosome at a slightly higher level than denominator elements are produced by autosomes. When the X:A ratio is 1 (in females), there are too many numerator elements to be occupied by denominators, and those not sequestered can form homodimers, which act as activators of the Sxl gene. When the X:A ratio is 1/2 (in males), there are fewer numerators than denominators, and all the numerators become sequestered. The Sxl protein triggers a cascade of splicing of transformer (tra) and double-sex(dsx) mRNAs o Sxl proteins regulate the splicing of tra mRNA o Tra protein regulates splicing of dsx mRNA o o (aThe presence of Sxl alters the splicing of tra mRNA. Female transcripts produce functional Tra protein, while male transcripts have a truncated open reading frame and are unable to produce Tra. (b) Tra protein, in turn, plays a role in altering the splicing pattern of the dsx mRNA. A different Dsx product results in males (Dsx-M) rather than in females (Dsx-F). o Dsx-F is a transcriptional activator and Dsx-M is a transcriptional repressor o The Tra protein regulates splicing of fruitless (fru) mRNA o o Splicing occurs unhindered in males to produce an mRNA, which is translated into the Fru-M protein product. But tra protein (present only in females) causes alternative splicing of the fru transcript to produce an alternative mRNA, which encodes an alternative protein product Fru-F. o the Fru-M protein  changes aggression, singing behavior for courtship and changes muscle function which allow the male to curve his abdomen and mate with the female RNA interference (RNAi) can phenocopy loss of function mutations 3 o example 1 : morpholinos in Zebrafish  Iln-41 silencing caused profound developmental defects in th
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