Genetica, al femminile: geni saltatori

Uno dei primi studi sulla ricombinazione genica è stato compiuto da una donna, Barbara McClintock, Premio Nobel nel 1983 per la Medicina e Fisiologia. Studiando l'ereditarietà di colore (antociani) nei chicchi del mais, pervenì alla formualzione della presenza di elementi mobili, Transposoni, capaci di regolare la escissione di sequenze di DNA dai cromosomi in siti di inserimento (long terminal repeats), per l'attività di un enzima di taglio e ligazione delle estremità di DNA, la trasposasi. Tali elementi sono all'origine dell'inserzione virale, e sono combattuti da altri elementi di difesa del genoma, come il sistema CRISPR, gli enzimi di metilazione differenziale del DNA, o l'espansione nel genoma umano delle sequenze Alu.

La professoressa McClintock era nota per la gentilezza e la disposizione all'ascolto, ed alla discussione.

• She developed the technique for visualizing maize chromosomes and used microscopic analysis to demonstrate many fundamental genetic ideas, including genetic recombination by crossing-over during meiosis—a mechanism by which chromosomes exchange information. She produced the first genetic map for maize, linking regions of the chromosome with physical traits, and demonstrated the role of the telomere and centromere, regions of the chromosome that are important in the conservation of genetic information

Figure 2: Variation in kernel phenotypes is used to study transposon behavior.

Kernels on a maize ear show unstable phenotypes due to the interplay between a transposable element (TE) and a pigment gene.

Copyright 2002 Nature Publishing Group, Feschotte, C., et. al., Plant transposable elements: Where genetics meets genomics, Nature Reviews Genetics 3, 339-341

• Barbara McClintock and the Discover of Jumping Genes (Transposons)
• © 2008 Nature Education
• Pray, L. & Zhaurova, K. (2008) Barbara McClintock and the discovery of jumping genes (transposons). Nature Education  1(1).
  
• Barbara McClintock began her scientific career at Cornell University, where she pioneered the study of cytogenetics—a new field in the 1930s—using maize as a model. Indeed, the marriage of cytology and genetics became official in 1931, when McClintock and graduate student Harriet Creighton provided the first experimental proof that genes were physically positioned on chromosomes by describing the crossing-over phenomenon and genetic recombination. Although Thomas Hunt Morgan was the first person to suggest the link between genetic traits and the exchange of genetic material by chromosomes, 20 years elapsed before his ideas were scientifically proven, largely due to limitations in cytological and experimental techniques (Coe & Kass, 2005). McClintock's own innovative cytogenetic techniques were what allowed her to confirm Morgan's ideas, and these techniques are thus among her greatest contributions to science.

• Discovering TEs Through Experimentation with Maize

• ·         As previously mentioned, McClintock is best known not for her innovations in cytogenetic techniques, but rather for her discovery of transposable elements through experimentation with maize. In order to understand McClintock's observations (and logic) that led to her discovery of TEs, however, it's first necessary to be aware that the phenotypic system that McClintock studied—the variegated color pattern of maize kernels—involved three alleles rather than the usual two. Think of every maize kernel as essentially a single individual, originating as an ovule that undergoes (or has undergone) double fertilization (Figure 1). During double fertilization, one sperm fuses with the egg cell's nucleus, producing a diploid zygote that will develop into the next generation. Meanwhile, the other sperm fuses with the two polar nuclei to form a triploid endosperm. As a result, the colored (or colorless, as the case may be) tissue that makes up the aleurone (or outer) layer of the endosperm is triploid, not diploid.

   

  ·         McClintock worked with what is known as the Ac/Ds system in maize, which she discovered by conducting standard genetic breeding experiments using plants with an unusual phenotype. Through these experiments, McClintock recognized that breakage occurred at specific sites on maize chromosomes. Indeed, the first transposable element she discovered was a site of chromosome breakage, aptly named "dissociation" (Ds). Although McClintock eventually found that some TEs can "jump" autonomously, she noted that the movements of Ds are regulated by an autonomous element called "activator" (Ac), which can also promote its own transposition.

  ·         Of course, these discoveries were preceded by extensive breeding experimentation. It was known at the time from previous work by Rollins A. Emerson, another American maize geneticist, that maize had genes encoding variegated, or multicolored, kernels; these kernels were described as colorless (although they were actually white or yellow), except for spots or streaks of purple or brown (Figure 2). Emerson had proposed that the variegated streaking was due to an "unstable mutation," or a mutation for the colorless phenotype that would sometimes revert back to its wild-type variant and result in an area of color. However, he couldn't explain why or how this occurred. As McClintock discovered, the unstable mutation Emerson puzzled over was actually a four-gene system, as outlined in Table 1

  ·         Table 1: Maize Genes Studied by Barbara McClintock

• Gene	Description
  C'	Dominant allele on the short arm of chromosome 9 that prevents color from being expressed in the aleurone layer of the maize kernel, causing a so-called "colorless" phenotype (which is actually white or yellow in color). This is also known as the inhibitor allele.
  C	Recessive allele on the short arm of chromosome 9 that leads to color development.
  Bz	Dominant allele on the short arm of chromosome 9 that leads to a purple phenotype.
  bz	Recessive allele on the short arm of chromosome 9 that leads to a dark brown phenotype.
  Ds	Genetic location on the short arm of chromosome 9 at which chromosomal breakage occurs.
  As	A factor of unknown location (at least when McClintock was conducting her research) that impacts the expression of Ds.