Meiosis

Meiosis begins like mitosis, with a single round of DNA replication, but is followed by two consecutive divisions rather than one. The result is four haploid cells, each with half the chromosome number of the parent cell and none genetically identical to it. In humans this converts a diploid germ cell with 46 chromosomes into gametes with 23, so that fertilization restores the diploid number rather than doubling it each generation.

The two divisions do different jobs. Meiosis I is reductional: homologous chromosomes pair along their lengths in prophase I, line up as bivalents at the metaphase plate, and are pulled to opposite poles in anaphase I. Sister chromatids stay together. Meiosis II is equational and closely resembles mitosis: sister chromatids finally separate, producing four haploid cells from the two cells that meiosis I created.

Three mechanisms generate the variation. Crossing over during prophase I exchanges segments between homologous chromosomes at chiasmata, producing recombinant chromatids. Independent assortment in metaphase I means each homologous pair orients randomly relative to the others, giving 2²³ possible combinations in humans before recombination is even counted. Random fertilization then combines two independently assorted gametes. Errors in the process matter clinically: failure of chromosomes or chromatids to separate — nondisjunction — produces gametes with an extra or missing chromosome, and the resulting aneuploidies include trisomy 21, trisomy 18, trisomy 13, Turner syndrome (45,X), and Klinefelter syndrome (47,XXY). Maternal age is associated with increased nondisjunction risk, in part because primary oocytes remain arrested in prophase I for decades.

Timing also differs by sex. Spermatogenesis yields four functional sperm per starting cell and runs continuously after puberty; oogenesis yields one ovum plus polar bodies, arrests in prophase I before birth, and completes meiosis II only if fertilization occurs. The MCAT tests meiosis in its biology and biochemistry sections as the basis of heredity and genetic diversity, and USMLE Step 1 approaches it through genetics — particularly nondisjunction and the chromosomal disorders it produces.