12.5: Recombination and independent segregation

We begin our description of meiosis (↓) with a diploid germ line cell that contains two copies of each autosome and, in mammals, either two X chromosomes or an X and a Y chromosome. The chromosomes delivered to the fertilized egg and subsequent zygote by a female gamete are known as maternal chromosomes, while those delivered by the male gamete are known as as paternal chromosomes. The maternal and paternal chromosomes are known as homologs. To generate gametes, a diploidgerm-line cell enters meiosis (see video link). Meiosis consists of a single round of DNA replication followed by two rounds of cell division.

As the diploid germ line cell enters meiosis it moves from G1 into S, just as in mitosis. Each of its individual chromosomes is duplicated. The resulting replicated (double-stranded) DNA molecules remain attached to one another through a structural complex known as the centromere. Here is where meiosis diverges from mitosis. In an asexual (mitotic) cell division each replicated chromosome remains independent of its homolog and each replicated chromosome interacts independently with the mitotic spindle through its centromere and associated kinetochore complex. In meiosis, during G2 the now duplicated homologs (the maternal and paternal chromosomes) align with one another (→). These four DNA molecules are known historically as a “tetrad”; each consists of four double-stranded DNA molecules. The pairing of the homologous chromosomes is based on the association of syntenic chromosomal regions.^[449] The DNA sequences along the homologous chromosomes, while not identical, are extremely similar, with the same genes located in the same order on each. When they are not, due to chromosomal rearrangements, things can get messy - as we will see. After chromosome pairing, and at essentially random positions along the length of the chromosomes, "crossing-over" or recombination events can occur. A DNA endonuclease, produces double-strand breaks in two of the four (double-stranded) DNA molecules (for example, at the site marked by “X” above ↑).^[450] The DNA molecules are then rejoined, either back to themselves (maternal to maternal, paternal to paternal) or to the other DNA molecule. Maternal to maternal or paternal to paternal crossing over events are generally invisible and have little impact. Crossing-over between homologs (paternal to maternal or maternal to paternal) lead to visible (←) crossing-over events. Typically, multiple “cross-over” events occur along the length of each set of paired (replicated) homologous chromosomes. Whenever maternal-paternal crossing over occurs the resulting "recombinant chromosome" contains a different set of alleles than either the original chromosomes. You can convince yourself by following any one DNA molecule from beginning to end.

In addition to shuffling alleles, crossing over can create new alleles. Consider the situation in which two alleles of a particular gene are different from one another (→). Assume that each allele contains a distinct sequence difference (as marked). If, during meiosis, a crossing over event takes place between these sites, it results in one allele that contains both molecular sequences (AB), and another allele with neither (indicated as wild type "WT"). A new allele (AB) has been created, without a new mutation!

In the case of the X and Y chromosomes, the chromosomes pair with one another through their common pseudo-autosomal regions (see above), which are syntenic. Outside of these regions there is no significant synteny between the X and Y chromosomes, so crossing-over does not occur. In contrast, crossing occurs normally (that is, just like for autosomes) between the two X chromosomes in females.

Meiosis leads to yet another source of variation. At the first meiotic division, the duplicated (and recombined) homologous chromosomes remain attached at their centromeres; each of the tworesulting daughter cells receives either the duplicated maternal or paternal chromosome centromere region. However, what set of chromosomes (defined by their centromeres, maternal or paternal) they inherit is determined by chance. The process is known as the independent assortment of homologous chromosomes during the first meiotic division, or independent assortment for short (←). For an organism with 23 different chromosomes (such as humans), the first meiotic division can produce 2²³ (8,388,608) different daughter cells.

There is no DNA replication between the first (M1) and the second (M2) meiotic divisions. During the second meiotic division each replicated chromosomes, held together at their centromere, attach to the spindle, very much as in mitosis. But because of earlier recombination events, the two chromosomes are no longer necessarily identical. This further increases to rather astronomical levels the number of different chromosome sets a particular haploid gamete can inherit. When the chromosomes separate, each of the two resulting sibling cells receives one and only one copy of each chromosome. Which particular chromosomes they inherit is stochastic. In males, all four haploid cells form gametes; they differentiate into sperm, that can fuse with an egg cell. In females only one of the four haploid cells forms a gamete, differentiating to form an oocyte that becomes a haploid egg that can fuse with a sperm cell. The other three haploid cells produced are known as polar bodies. Polar bodies do not fuse with sperm, they donate their cytoplasm to the oocyte - supporting the development of a large, fertilizable gamete.

The result, and basically the point, of meiosis is to generate a population of gametes in which the alleles present in the maternal and paternal chromosomes have been shuffled in various ways, so that any resultant offspring have a unique genomes related to, but distinct from that of either of their parents.^[451] Fertilization (the fusion of gametes) combines two such genomes, one maternal and one paternal, to form a new organism, with a novel combination of alleles generated through independent assortment of homologous maternal and paternal chromosome and recombination events. Most phenotypes are influenced, to a greater or lesser degree, by the set of alleles within a genotype, and new combinations of alleles will lead to new phenotypes and phenotypic variations that can impact reproductive success, and so lead to evolutionary effects.

---