Non-random segregation of chromosomes is a deviation from the usual distribution of chromosomes during meiosis, that is, during segregation of the genome among gametes. While usually according to the 2nd Mendelian rule (“Law of Segregation of genes“) homologous chromosomes are randomly distributed among daughter nuclei, there are various modes deviating from this in numerous organisms that are "normal" in the relevant taxa. They may involve single chromosome pairs (bivalents) or single chromosomes without mating partners (univalents), or even whole sets of chromosomes, in that these are separated according to their parental origin and, as a rule, only those of maternal origin are passed on to the offspring. It also happens that non-homologous chromosomes segregate in a coordinated manner. As a result, this is a form of Non-Mendelian inheritance.

This article describes cases where non-random segregation is the normal case for the particular organisms or occurs very frequently. A related phenomenon is called meiotic drive or segregation distortion. This is a higher than average transmission of a single chromosome relative to the homologous chromosome in inheritance. This can be due to non-random segregation during meiosis, but also to processes after meiosis that reduce the transmission of the homologous chromosome.

In addition, there are pathological cases that result in aneuploidy and are almost always lethal.

Background and early history of research

According to the chromosome theory of inheritance formulated by Theodor Boveri in 1904, homologous chromosomes were expected to be randomly distributed among the daughter nuclei during meiosis. The first studies on this question appeared in 1908 and 1909. These papers dealt with spermatogenesis in aphids, i.e. meiosis in the male sex. In aphids, sex determination is mostly done according to the XX/X0 type: females have two X chromosomes, males only one. However, males only appear in one generation towards the end of the year, while otherwise there are only females, which reproduce by parthenogenesis. The question now was how it is achieved that all offspring in sexual reproduction are females. It turned out that meiosis I is inequal, i.e. results in two unequal-sized cells, and the X chromosome always ends up in the larger daughter cell. Only from this cell do two sperm cells emerge after meiosis II, while the smaller cell degenerates. Thus, each sperm - like the egg - contains an X chromosome, and only female offspring (XX) are produced.Hermann Schwartz: Der Chromosomenzyklus von Tetraneura ulmi DE GEER. In: Zeitschrift für Zellforschung und Mikroskopische Anatomie 15, page 645–687 (1932)

Also in 1909, a paper was published on the spermatogenesis of Coreus marginatus. There are two different X chromosomes and no Y chromosome (X1X20), and in meiosis I both X chromosomes are assigned to the same daughter nucleus. The same is apparently generally true in spiders, many species of which have been studied in subsequent years, as well as in various nematodess and in some aphids.Michael J. D. White: The origin and evolution of multiple sex-chromosome mechanisms. In: Journal of Genetics 40, page 303-336 (1940) Thomas Hunt Morgan: The predetermination of sex in phylloxerans and aphids. In: Journal of Experimental Zoology 19, page 285-321 (1915) The situation is somewhat more complicated in the American mole cricket Neocurtilla hexadactyla, which Fernandus Payne described in 1916: Here, three sex chromosomes are present (X1X2Y), two of which mate, while X1 is present as a univalent (unpaired). Although, as recent studies have confirmed, there is no mechanical linkage, the univalent X chromosome enters the same daughter nucleus that receives the other X chromosome.Donna F. Kubai, Dwayne Wise: Nonrandom chromosome segregation in Neocurtilla (Gryllotalpa) hexadactyla: an ultrastructural study. Journal of Cell Biology 88, page 281–293 (1981)

It was only after all these counter-examples that a study by Eleanor Carothers on locusts appeared in 1917 - in the same journal as Payne's paper (Journal of Morphology) - which was seen as clear evidence for the expected random distribution. While earlier studies had been limited to sex chromosomes because homologous autosomes could not be distinguished, Carothers had found experimental animals in which homologous autosomes could also be partially distinguished. Payne's divergent findings were subsequently ignored, especially as they could not be confirmed in the European mole cricket. Thomas Hunt Morgan, who decisively contributed to the establishment of the chromosome theory of heredity, which was not yet generally accepted at that time, even explicitly wrote in his book The Physical Basis of Heredity (1919) that there was no contradictory evidence against the random segregation of maternal and paternal chromosomes (there is not a single cytological fact opposed to the free assortment of maternal and paternal chromosomes), although he was undoubtedly aware of the work of his former collaborator Payne. It was not until 1951 that Michael J. D. White rediscovered it and confirmed it through his own investigations.Arthur Forer: Do chromosomes segregate randomly during meiosis?: Key articles by Fernandus Payne were ignored, and perhaps "suppressed". In: Proceedings of the American Philosophical Society 140, page 148–163 (1996)

The third basic variant of non-random segregation, in which the complete sets of chromosomes of maternal and paternal origin are separated from each other, was studied - among some other peculiarities - in the 1920s and 30s by Charles W. Metz and co-workers in fungus gnats.Charles W. Metz: Chromosome behavior, inheritance and sex determination in Sciara. In: American Naturalist 72, page 485–520 (1938) Since then, numerous other counterexamples to random segregation have been described in very different creatures. It was not until 2001, however, that a first review paper appeared that was devoted precisely to this topic and was not limited to specific cases. The authors stated that most geneticists are unaware of non-random segregations or consider them rare exceptions. Due to the wide taxonomic distribution of the known cases, they argue that the importance of these phenomena has been underestimated so far.Fernando Pardo-Manuel de Villena, Carmen Sapienza: Nonrandom segregation during meiosis: the unfairness of females. In: Mammalian Genome 12, page 331–339 (2001)

Single chromosomes or chromosome pairs We first consider cases where only a single chromosome pair or a single unpaired chromosome (univalent) is affected, in the order of first description in the respective taxon.

Aphids

As mentioned, the first example of non-random segregation described as early as 1908 was the behaviour of the X chromosome during spermatogenesis in aphids. These insects exist for most of the year only as females and reproduce parthenogenetically, i.e. without the participation of males. There is no fertilisation or meiosis, and successive generations are genetically identical. Under certain conditions, mostly due to the decreasing day length towards the end of the vegetation period of the host plants, one generation occurs in which males are also present. This is achieved by the two X chromosomes present in females mating as in meiosis and their number being reduced to 1, resulting in males (X0).

The fact that, after this one bisexual generation, only females are produced again is based, as shown above, on the fact that, during spermatogenesis, the X chromosome is always assigned to the daughter cell from which sperm are produced. Hans Ris described the exact sequence of meiosis in 1942:Hans Ris: A cytological and experimental analysis of the meiotic behavior of the univalent X chromosome in the bearberry aphid Tamalia (=Phyllaphis) coweni (Ckll.). In: Journal of Experimental Zoology 90, page 267–330 (1942) According to this, the X chromosome does not participate in the movement towards the poles of the spindle apparatus during anaphase, but is stretched between the diverging poles. Also during the subsequent cell division, the chromosome remains in this position. Only at a late stage of furrowing does the furrowing groove shift to one side, and the X chromosome is allocated to the opposite, larger daughter cell. Since only this produces two sperm, all sperm as well as the eggs contain an X chromosome. After fertilisation, eggs are laid, which survive until the beginning of the next growing season and then only produce females (XX), which again reproduce parthenogenetically.

Butterflies

In butterflies, the sex of the offspring is not determined as in the most common case among animals,Adolf Remane, Volker Storch, Ulrich Welsch: Kurzes Lehrbuch der Zoologie. 5. Aufl., Fischer, Stuttgart 1985, page 291 including humans, but by the make-up of the egg. In these cases, the female sex is heterogametic, the male is homogametic. In such cases, one does not speak of X and Y chromosomes, but of Z and W chromosomes. Males have two Z chromosomes (ZZ), females either one Z and one W chromosome (ZW) or only one Z chromosome (Z0). An example of the ZZ/Z0 type is the Taleporia tubulosa. In this species, J. Seiler (1920), an associate of Richard Goldschmidt, studied the inheritance of sex and the behaviour of the univalent Z chromosome during oogenesis. He found that the sex ratio among the offspring depends on the temperature and the age of the mother. At cool temperatures ("room temperature of about 12-16°"), the Z chromosome entered the polar body in 57% of the cases studied at meiosis I and only in 43% in the future egg nuclei. Accordingly, Seiler found an excess of females in the offspring. Conversely, when the chromosome was preferentially allocated to the egg in the incubator at 30-37°, there was a surplus of 62 % male offspring. Similarly, more males were produced when mating occurred a few days after hatching and thus towards the end of the short life of the female Imago.J. Seiler: Geschlechtschromosomenuntersuchungen an Psychiden. I. Experimentelle Beeinflussung der geschlechtsbestimmenden Reifeteilung bei Talaeporia tubulosa Retz. In: Archiv für Zellforschung 15, page 249–268 (1920) (Meiosis pauses here, as in most invertebrates, in metaphase I and is not completed until after fertilisation. Cf. Stasis of female meiosis). Evidence of non-random segregation in female meiosis has also been found in butterflies of the ZZ/ZW type. In some species of the genera Danaus and Acraea there are females that produce only female offspring (ZW). This is apparently due to the fact that the W chromosome always enters the egg cell and not the polar bodies. This modification of the meiotic chromosome distribution is hereditary and linked to the W chromosome.Terrence W. Lyttle: Segregation distorters. In: Annual Review of Genetics 25, page 511–557 (1991)

Fungus gnats The fungus gnats, whose spermatogenesis has some peculiarities (summary at fungus gnat#genetics), have already been mentioned. In meiosis II, a peculiarity occurs with the X chromosome. Normally, in meiosis II (as in mitosis), all chromosomes are divided into the two chromatids that make them up and these are allocated to the two daughter nuclei. In fungus gnats, on the other hand, the X chromosome travels prematurely to one of the spindle poles and only divides there or on the way there. Since a sperm is only produced from the cell formed there, this then contains two X chromosomes, and the zygote after fertilisation accordingly three. One of these X chromosomes is eliminated at an early embryonic stage, thereby restoring the normal female chromosome make-up (XX).

Flowering plants