3 Chromosomes, Meiosis, and Linkage

Chromosome organization

A eukaryotic chromosome is a long DNA molecule packaged with proteins, especially histones. DNA and its associated proteins form Chromatin. Before cell division, each chromosome is copied; its two identical DNA molecules are sister chromatids, joined at the centromere. Telomeres protect chromosome ends, and a gene occupies a specific chromosome position called a locus.

In a diploid organism, chromosomes occur as Homologous chromosomes: one homolog in each pair comes from each parent. Homologs carry the same genes at corresponding loci, but they may carry different alleles. They are not identical copies; sister chromatids are generally identical except where recombination has exchanged DNA.

How meiosis divides chromosomes

Meiosis produces haploid reproductive cells, or gametes, from a diploid cell. DNA replicates once before meiosis, which then proceeds through two divisions.

• Meiosis I separates homologous chromosomes. In prophase I, homologs pair along their lengths. In metaphase I, each pair aligns at the cell’s middle; each pair’s orientation is independent of the orientations of other pairs. In anaphase I, homologs move to opposite poles while sister chromatids remain joined. This division halves the chromosome number.

• Meiosis II separates sister chromatids. They are pulled to opposite poles in a process similar to chromosome separation in mitosis.

Meiosis usually produces four haploid cells. Each receives one chromosome from each homologous pair, but the chromosomes can carry new combinations of parental DNA. At fertilization, a haploid egg and haploid sperm each contribute one chromosome of each pair, restoring the diploid number.

Takeaway: Meiosis I separates homologs; meiosis II separates sister chromatids.

Two sources of genetic variation

Independent assortment is the independent orientation of chromosome pairs in meiosis I. With $n$ chromosome pairs, it can produce up to $2^n$ combinations of whole chromosomes in gametes, before crossing over is considered. For $23$ pairs, that is $2^{23}$ possible combinations of maternal and paternal homologs.

Another source of variation is Crossing over. During prophase I, paired homologs can exchange corresponding DNA segments between nonsister chromatids. This exchange creates recombinant chromatids and helps connect homologs until they separate in meiosis I. For example, if homologs carry allele combinations $\mathrm{AB}$ and $\mathrm{ab}$, a crossover between the loci can produce $\mathrm{Ab}$ and $\mathrm{aB}$.

Takeaway: Independent assortment reshuffles whole chromosomes; crossing over reshuffles DNA segments within homologous chromosomes.

Linkage and estimating distance

Linkage describes the tendency of genes on the same chromosome to be inherited together. The closer two loci are, the less likely a crossover will occur between them. Loci farther apart are more likely to be separated by recombination. Genes on different chromosome pairs generally assort independently.

The Recombination frequency is the percentage of offspring with recombinant allele combinations:

For nearby loci, $1\%$ recombination is approximately $1$ map unit, or $1$ centimorgan (cM). Recombination frequency cannot exceed $50\%$. Loci near that value behave as if unlinked: they may be on different chromosomes or far apart on the same chromosome. Multiple crossovers can obscure recombination between distant loci, so map distance is an estimate rather than a direct measurement of physical DNA length.

Takeaway: More recombination between two loci generally indicates greater separation, but recombination frequency has limits as a measure of distance.

When chromosome segregation goes wrong

Nondisjunction is the failure of homologs or sister chromatids to separate correctly. It can produce gametes with an extra or missing chromosome. If such a gamete is fertilized, the resulting cell may have Aneuploidy, an abnormal chromosome number.

Together, chromosome packaging, meiotic separation, independent assortment, crossing over, and chromosome segregation determine which parental chromosome combinations are transmitted to offspring. Genes on the same chromosome may not be inherited independently because of linkage, while errors in segregation can alter chromosome number.