THE GENETICS OF THE MAMMALIAN GAMETE
Authors: BEATTY R. A. 
Published: January 2008

1. Study of the association of the somatic and gametic genotypes with the gametic phenotype has been termed the genetics of gametes. The latter is closely associated with problems of fertility and infertility; with the general validity of the postulate of random union of the gametes; with experimental attempts to control sex ratio or other Mendelian segregations; and with the study of chromosomal anomalies. Effects of the post‐segregational genotype (after meiosis) are of exceptional interest.

2. The dimensions of mammalian spermatozoa show numerous patterns of genetic behaviour, such as strain and breed differences, additive variation, heterosis, high heritability, maternal effects, and a tentative ‘paternal cytoplasmic effect’. The high degree of additive genetic determination is reflected in the smooth progress of a genetic selection programme that brought into existence strains of mice with either long or short spermatozoan midpieces. The balance sheet of variation in mammalian spermatozoan dimensions is as follows. Apart from the natural variation between individual spermatozoa of a male, the paramount factors are the genetic ones. Variation is extraordinarily independent of other biological sources of variation and of environmental ones. The high heritability of most spermatozoan dimensions suggests that they are not closely associated with reproductive fitness, whereas a measure of fitness (resistance of spermatozoa to eosin staining) shows a low heritability.

3. Post‐segregational gene action has been sought but not conclusively demonstrated in attempts to recognize X‐ and Y‐bearing spermatozoa visually, and in attempts to control sex ratio by separating them according to electrophoretic or sedimentation behaviour.

4. Variations in the DNA content of spermatozoa, and gross morphological defects, are associated with infertility and their incidence is often genetically controlled.

5. There is controversy over the balance between specific spermatozoan antigens and ‘coating antigens’ acquired from the seminal fluid. Reports that AB individuals (heterozygous for blood‐group antigens) produce phenotypically A and B spermatozoa would indicate post‐segregational gene action but are also controversial. Sex ratio has not yet been controlled by subjecting spermatozoa to anti‐Y‐chromosome antibodies. Genetic (strain) differences exist in spermatozoan antigens.

6. The incidence of non‐eosinophil spermatozoa is a measure of semen fertility. Strain and breed differences exist but the heritability is low. An absence of demonstrable genetic variation in spermatozoan motility may be due to a swamping effect of non‐genetic factors.

7. Diploid spermatozoa differ genetically and phenotypically from the normal haploid ones. The incidence of diploid spermatozoa is associated with infertility and is controlled genetically. The incidence of polyspermy and of supplementary spermatozoa are also controlled genetically.

8. Heterospermic (mixed) insemination from two or more sires discriminates efficiently between the sires in terms of the relative numbers of offspring produced. One experiment showed a genetic control (strain differences) in heterospermic performance. Heterospermic performance of a sire is constant over periods of time and is a predictor of the relative fertility obtained in ‘ordinary’ fertility tests. Heterospermic insemination per se has no apparent practical value.

9. Species crosses in animals tend to produce diploid oocytes and triploid embryos. ‘Foreign’ mammalian eggs or spermatozoa did not fertilize in the same proportion as native ones.

10. The most recent determination shows a I : I sex ratio in the very early embryo.

11. Mammals are scarcely likely to be exempt from certain unorthodox genetic mechanisms, but positive evidence is only indicative. Micro‐organisms have been detected and sometimes have a genetic role in spermatozoa and eggs of animals. There is a theory that mitochondria (and therefore most of the spermatozoan midpiece) are modified bacteria. A tentative ‘paternal cytoplasmic effect’ on mouse spermatozoan dimensions, mediated by mitochondria1 inheritance, has been invoked. Conditions may exist for possible transfer of genetic information from spermatozoa to body cells via leucocytes. There is no confirmation of experiments for transfer of genetic information by injection of DNA of specific genotypes prepared from spermatozoa or other tissues.

12. The behaviour of ‘tailless’ alleles in mice provides a unique example of post‐segregational gene action, the t‐spermatozoa of heterozygous Tt males yielding more offspring than the T‐spermatozoa. This work explains the aberrant transmission of t through the male parent, and also the high frequency of the allele in wild populations. It is the best example of post‐segregational gene action in animals, provides an exception to the random union of gametes, and permits a novel way of controlling the transmission of genetic information between generations. There is presumptive post‐segregational gene action in other segregations in mouse and man.

13. The study of heteroploidy (abnormal chromosome numbers) provides massive evidence of anomalies in the mammalian egg that are in themselves genetic (e.g. diploidy) and phenotypic (e.g. abnormal numbers of polar bodies or pronuclei); that come into being under genetic control, and that have genetic consequences (e.g. triploidy) and phenotypic ones (e.g. inviability) for the embryo. This is illustrated by suppression of the cytoplasmic second meiotic division of the egg, giving diploid parthenogenetic embryos from unfertilized eggs and triploid ones from fertilized eggs. Triploidy is the dominant form of polyploidy in vertebrates. Triploidy is lethal in the mammalian embryo and is a main cause of the ‘natural’ level of prenatal mortality in man.

14. The groups of cells produced by meiosis in both sexes of animals are virtually syncytial. This has a bearing on post‐segregational heterosis and gene effects.

15. The unique and apparently indisputable instance of post‐segregational gene action in ‘tailless’ mice is to be contrasted on the one hand with numerous persuasive arguments (especially effective in Drosophila) that such action cannot or does not occur in animals or else is mimicked by another phenomenon, meiotic drive; and on the other hand contrasts with an hypothesis that post‐segregational gene action occurs on a gigantic scale in all organisms in which crossing‐over takes place. It is concluded for the time being that post‐segregational gene action does occur in mammals, but is rare. Because of the rarity, a reasonable first interpretation in all gamete genetics is that gene action is mediated by the somatic genotype, unless there are specific reasons to the contrary. There is urgent need for a technique whereby the biological potential of a given spermatozoon can be recognized by fertilizing a given egg with it.

16. As a series of working hypotheses, it is proposed that the general architecture and course of differentiation of gametes are determined by the genotype of the soma and the same pre‐segregational genotype of the germ line, the initial gene action being a synthesis of messenger RNA before meiosis in the germ line or at any time in the soma. These effects of the somatic genotype bring the gamete into existence and are also responsible for most of the widespread variation in its phenotype. The gamete so produced can be varied by a very few genes or sets of genes synthesizing messenger RNA in the germ cells after segregation, or else exerting action in some other way connected with their direct physical and chemical nature or their arrangement. These post segregational effects are more likely to be mediated by whole blocs of genes, especially heterochromatic and nucleolar ones, than by ‘billiard‐ball’ single genes in the narrow sense.