Sources of Genetic Variation in Meiosis

Genetic variation in meiosis comes from three sources: crossing over between homologous chromosomes, independent assortment of chromosomes into gametes, and the random fusion of gametes at fertilization. In brief: independent assortment alone allows 2²³ (about 8.4 million) different gametes in a human, crossing over greatly increases this number, and random fertilization multiplies the possibilities again. Errors in chromosome separation, called nondisjunction, can produce gametes with too many or too few chromosomes.

Variation is the raw material for natural selection, so the mechanisms of meiosis are central to evolution. This guide explains each source of variation, with calculations, compares mitosis and meiosis, describes what happens when chromosomes fail to separate, works through a numerical example and corrects common mistakes.

How does crossing over create variation?

In prophase I, homologous chromosomes pair up. The enzymes cut non-sister chromatids at matching points and swap segments, which creates new combinations of alleles on the same chromosome. This is called genetic recombination. The points where chromatids cross are the chiasmata. In humans, there are on average 1 to 3 crossovers per chromosome pair, and about 50 in total in a cell undergoing meiosis.

For example, suppose a chromosome from the mother has alleles A and B, and the homologous chromosome from the father has a and b. Without crossing over, gametes would carry only AB or ab. If a crossover occurs between the genes, some gametes will carry Ab or aB. These are recombinant gametes. Genes that are far apart on a chromosome are recombined often, and genes that are close together are recombined rarely. This is the basis of gene mapping, as described in a later article.

How does independent assortment create variation?

In metaphase I, each pair of homologous chromosomes lines up at the equator, and which member of the pair faces which pole is random. In anaphase I, the members of each pair go to different poles. For each pair, the orientation is independent of the others. A cell with n pairs of chromosomes can produce 2ⁿ different combinations of maternal and paternal chromosomes.

• For n = 2: 2² = 4 combinations.
• For n = 3: 2³ = 8 combinations.
• For humans, n = 23: 2²³ = 8 388 608 combinations.

How does random fertilization add variation?

Any sperm can fuse with any egg. Each person produces millions of genetically different sperm or eggs, so which two gametes meet is a matter of chance. With only independent assortment, the number of different zygotes from one couple is (2²³)² ≈ 7 × 10¹³. This explains why siblings (except identical twins) are different from each other. In practice, the number is even greater because of crossing over. Mutation adds new alleles, another important source of variation that is independent of meiosis.

Sources of variation compared

Worked example: how many possible offspring?

An organism has 2n = 6 chromosomes (3 pairs). Each pair has one chromosome from the mother (M) and one from the father (P): pairs 1, 2 and 3.

1. Gametes from independent assortment: the choices are M1 or P1, M2 or P2, and M3 or P3. Number of combinations: 2 × 2 × 2 = 8. They are M1M2M3, M1M2P3, M1P2M3, M1P2P3, P1M2M3, P1M2P3, P1P2M3 and P1P2P3.
2. Fraction that are completely maternal or completely paternal: 2 out of 8, which is 1/4. The probability that a gamete has all three chromosomes from the same grandparent is 1/4.
3. Zygotes from two parents with 3 pairs each: 8 × 8 = 64 different chromosome combinations, even without crossing over.
4. Humans: the probability that a gamete carries only the chromosomes inherited from one grandparent, for example only maternal ones, is (1/2)²³ = 1 in 8 388 608.

The calculation shows that almost every gamete is a mixture of chromosomes from both grandparents. When crossing over is included, each chromosome is itself a mosaic, so a child’s DNA is a unique combination.

What happens when chromosomes fail to separate?

Nondisjunction is a failure of homologous chromosomes (in meiosis I) or sister chromatids (in meiosis II) to separate properly. The gametes then have an extra chromosome (n + 1) or a missing chromosome (n − 1). If such a gamete is involved in fertilization, the zygote has 2n + 1 (trisomy) or 2n − 1 (monosomy).

• Down syndrome (trisomy 21): three copies of chromosome 21, giving 47 chromosomes. The chance rises with the mother’s age, from roughly 1 in 1 500 births at age 20 to about 1 in 100 at age 40.
• Turner syndrome (45,X): a female with only one X chromosome.
• Klinefelter syndrome (47,XXY): a male with an extra X chromosome.

Most embryos with an abnormal number of chromosomes do not survive, and are a leading cause of early miscarriage. Chromosome abnormalities are covered in a later article on karyotypes.

How does meiosis compare with mitosis?

Mitosis produces genetically identical cells and no new variation, except by mutation. Meiosis produces genetically different cells, through crossing over and independent assortment. This is why sexual reproduction, which uses meiosis, produces variation, while asexual reproduction, which uses mitosis, produces clones. Variation helps populations to adapt: if the environment changes or a new disease spreads, some individuals may have combinations of alleles that give them an advantage.

How were the sources of variation discovered?

Thomas Hunt Morgan’s group in the early 1910s showed that linked genes can be separated and recombined. Barbara McClintock and Harriet Creighton demonstrated physical crossing over in maize chromosomes in 1931. Calvin Bridges demonstrated nondisjunction in fruit flies in 1916, which provided the first proof that genes are carried on chromosomes. Jérôme Lejeune and colleagues found in 1959 that Down syndrome is caused by an extra chromosome 21.

Which mistakes are common?

Mistake 1: Saying that crossing over happens between sister chromatids

The exchange that creates variation occurs between non-sister chromatids of homologous chromosomes.

Mistake 2: Mixing up the timing

Crossing over happens in prophase I. Independent assortment happens in metaphase I and anaphase I.

Mistake 3: Saying that mutation is part of meiosis

Mutation is a separate source of variation. It can happen at any time, not only during meiosis.

Mistake 4: Thinking that nondisjunction creates new alleles

It changes chromosome number, not the sequence of genes.