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CELL BIOLOGY: ON MEIOTIC RECOMBINATION

In this context, the term "diploid" refers in general to a chromosome state in which each type of chromosome is represented twice. In contrast, the term "haploid" refers to a chromosome state in which each chromosome is represented singly. In humans, somatic cells are diploid and gametes are haploid.

In this context, the term "meiosis" (reduction division) refers to the process whereby a nucleus divides by two divisions (meiosis I and meiosis II) into four nuclei, each containing half the original number of chromosomes, in most cases forming a genetically nonuniform haploid. This is a necessary aspect of eukaryotic sexual reproduction, for without it fertilization would usually double the chromosome number every generation.

The following points are made by E.J. Louis and R.H. Borts (Current Biology 2003 13:R953):

1) Meiotic cell division is specialized to separate homologous chromosomes into the haploid germ cells. The accurate segregation of chromosomes in meiosis, and consequent reduction of ploidy from 2N to 1N, depends on their being sufficient, properly distributed crossovers, or recombination sites. This process involves an intricate set of chromosomal and DNA interactions (1,2).

2) At a gross chromosomal level, the homologous chromosomes exhibit transient interactions that progress to pairing along their lengths. This culminates in the construction of a highly ordered proteinaceous structure called the "synaptonemal complex", and concomitantly physical connections called "chiasmata" are formed. These provide the tension necessary for proper alignment of the homologues on the meiosis I metaphase spindle, and are revealed only after the synaptonemal complex has broken down and the chromosomes are pulled to opposite poles.

3) Chiasmata are sites of DNA exchange -- crossovers -- between the homologues. They are non-randomly distributed as a result of a mysterious process termed "interference", such that all chromosomes obtain at least one crossover necessary for proper disjunction of the homologues. In most organisms studied, too few crossovers or crossovers in the wrong places can lead to aneuploidy as a result of missegregation (3).

4) A "Holliday junction" (Holliday structure) is one of the junctions between four strands of DNA that are important intermediates in genetic recombination. At the DNA level, meiotic recombination initiates as double-strand breaks which are processed through several steps. These include strand resection, one-ended single-strand invasion of homologous sequences, priming of DNA synthesis from the invasion, second-end capture, and the formation of double "Holliday junctions", followed by resolution as a crossover (4,5). More double-strand breaks are made than result in crossovers, though non-crossover interactions still result in recombination -- these can be detected genetically by non-Mendelian segregation patterns such as gene conversions. At some stage, therefore, many events are processed into non-crossovers without maturing into fully ligated double Holliday junctions. The big questions that remain to be answered are when, and how, the decision to be, or not to be, a crossover is made.

5) A number of genes have been identified in which mutations cause a reduction in crossovers and/or a loss of interference, resulting in the production of aneuploid gametes (1-3,5). But until very recently, we knew of no genes where loss of function led to an increase in meiotic crossing over. This has changed with the recent evidence of Rockmill et al (2003), who have shown that the budding yeast RecQ helicase SGS1 has a meiosis-specific role in limiting the number of crossovers.

References (abridged):

1 Roeder, G.S. (1997). Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600-2621

2 Zickler, D. and Kleckner, N. (1999). Meiotic chromosomes: integrating structure and function. Annu. Rev. Genet. 33, 603-754

3 Hassold, T., Sherman, S., and Hunt, P. (2000). Counting cross-overs: characterizing meiotic recombination in mammals. Hum. Mol. Genet. 9, 2409-2419

4 Hunter, N. and Kleckner, N. (2001). The single-end invasion: an asymmetric intermediate at the double-strand break to double-holliday junction transition of meiotic recombination. Cell 106, 59-70

5 Allers, T. and Lichten, M. (2001). Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106, 47-57

Current Biology http://www.current-biology.com

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ON OOGENESIS

The following points are made by W.M. Becker and D.M. Deamer (citation below):

1) Egg development varies from species to species in details, but usually follows [a general scheme]. Oogenesis begins after the primordial germ cells migrate to the gonad and become oogonia. A finite number of mitotic divisions occur; in the human female, these divisions are complete before birth. Many more potential eggs are generated than will ever be shed; thus most oogonia regress and die before they complete oogenesis. When the final number of oogonia is obtained, the chromosomes replicate and the cells differentiate into primary oocytes, which enter prophase of the first meiotic division. At this stage, meiosis is usually arrested, and each oocyte enters a resting state until the female becomes sexually mature. This can take anywhere from a few days to many years, depending on the species.

2) At sexual maturity, hormones direct primary oocytes to mature one (or a few) at a time. The nuclear membrane of the oocyte is known as the germinal vesicle. The steroid hormone progesterone triggers oocyte maturation, causing germinal vesicle breakdown and the completion of meiosis I. Nuclear division is equal, but the cytoplasm divides very unequally, producing one large secondary oocyte, from which the egg will eventually arise, and a small polar body. Division of the large secondary oocyte is again very unequal, as meiosis II generates another small polar body and the large ootid, which develops into the ovum.

3) Because both meiotic divisions are very unequal, the ovum retains more than 95% of the cytoplasm of the primary oocyte. Oocytes are one of the largest cell types. This makes sense because the ovum must supply almost all of the cytoplasm and initial food supply for the embryo that is formed upon fertilization. In contrast, the only known contribution of the sperm cell is its genetic material and the minimal contents of the male pro-nucleus.

Adapted from: W.M. Becker and D.M. Deamer: The World of the Cell. 2nd Edition. Benjamin/Cummings 1991, p.675. More information at: http://www.amazon.com/exec/obidos/ASIN/0805308709/scienceweek

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