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Example of Transformative Research

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Will that be allele cache or Mendelian credit? Evidence for the inheritance of ancestral sequences in Arabidopsis. Susan J. Lolle Purdue University National Science Foundation Arabidopsis wild-type Fusion mutants FIDDLEHEAD defined a class of mutations that resulted in ectopic organ fusion Two heads are better than one... hothead - phenotype • Organ fusion • Pollen hydration on vegetative surfaces • Increased rate of chlorophyll extraction • Limited self-fertility hth-10 All hothead mutations are recessive Both copies of the gene must have a mutation to reveal the mutant phenotype Fundamentals of Mendelian Genetics • Two alleles per locus • Alleles can be dominant or recessive • Alleles are stable from one generation to the next, whether or not they contribute to the observed phenotype Self-fertilizing verses Cross-fertilizing Progeny should all be homozygous hothead Stable Inheritance 100% parent progeny But, some progeny are wild-type! 90% 10% Mechanism? Arabidopsis wild-type Fusion mutant Sequencing of HOTHEAD •All mutant alleles contain a single point mutation in the HOTHEAD gene •Columbia and Landsberg wild-type alleles very similar; Ws quite different Using Molecular Markers to Genotype Allele „A‟ PCR amplify (using specific primers) Allele „a‟ Restriction Enzyme Digestion Gel electrophoresis Does phenotype relate to genotype? Does phenotype relate to genotype? What does the sequence tell us? I don’t know if this is such a wise thing to do, Bob. Is reversion really contamination? Is this a mistake? •Seed contamination due to wild-type plants grown in close proximity to mutants •Elevated levels of outcrossing in hothead mutants (who is the daddy?) Embryonic revertants hth-4/hth-4 HTH/HTH parent # of embryos % 2 <1 HTH/hth 57 16 hth/hth 301 84 •Revertants detected as embryos cannot be due to contaminating seed Explanations for Genetic Instability What does the sequence tell us? •Transposon-induced alleles •Inverted or direct repeats at the locus •Epigenetic alleles •High rate of random mutation •Gene conversion Gene conversion with other family members HTH hth-10 At HTH-like At HTH-like At HTH-like At HTH-like At HTH-like At HTH-like At HTH-like 1 2 3 4 5 6 7 ACT ACT GTT CCA CCA GTC GCC GCT GTC GTT GTT GTT CCT CCT GTG GTA GTT GTT GGA GAA GGG CAA CAA GGT GGA GGG GGA ATT ATT ATT GTT GTT GTT ATC ATC ATC ACA ACA ACC GTA GCA ACT ACC ACA ACA •None of these sequences could provide correction of the mutant nucleotide without introducing other changes Instability of molecular markers in hth background Marker AG GAPC GL1 hth/hth 4% (7/186) 4% (9/242) 1% (1/90) HTH/HTH 0% (0/190) 0% (0/190) 0% (0/196) Location in gene intron intron 3’-UTR HTH RGA UFO 2% (10/484) 3% (14/402) 4% (16/438) 0% (0/590) 0% (0/386) 0% (0/196) exon exon exon Where did these sequences come from? • They were not present in the parental genome  molecular and genetic evidence • They were present in the ancestors  molecular and genetic evidence A DNA template cannot be detected in the parental genome Evidence strongly supports a ‘template-directed’ process. Is the template RNA? Where is it? How long does it persist? What might this mean? “@$#?!$” •Organisms could carry sequence information for more than two alleles •Mechanism might help selffertilizing species avoid the negative consequences of inbreeding Should you worry about your ancestry? How long does the allele cache persist? Is it quality cache? Acknowledgements National Science Foundation Collaborator: Bob Pruitt People: Katie Krolikowski Ryan Lee Tina Nussbaum Wagler Liese Pruitt Trulie Thorley Mirayda Torres Jen Victor Jessica Young
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