images of dye-stained nuclei from horse lymphocytes (white blood cells) undergoing cell division (image: T.L. Lear).
Genes in mitochondria
In addition to the DNA in chromosomes, each cell has a pair of small, circular DNA molecules in their mitochondria. Mitochondria are small organelles in the cell important for oxidative metabolism. Horses have 37 mitochondrial genes, all of which are dedicated to the function of mitochondria. The mitochondria in an offspring usually originate from the eggs of the dam. The mitochondria in sperm are almost always lost. Consequently, the inheritance of mitochondrial DNA and mitochondrial genes follows the maternal line of inheritance (Chapter 21 has more information about mitochondria genetics)
Behavior of Chromosomes
The behavior of chromosomes through cell life cycles is the key to the principles of Mendelian inheritance. Two types of division cycles are characteristic of vertebrates. The first process (mitosis) occurs in all cells of the body. The second chromosome process (meiosis) is directly involved in the formation of the gametes (sperm and eggs) and occurs only in the reproductive organs or gonads (testes in males and ovaries in females).
In Fig. 4.4, the large mass to the right of the image is a large, intact nucleus. The smaller, dark staining bodies are chromosomes which have burst from another cell’s nucleus. Each contains tightly coiled DNA from one of the 64 horse chromosomes. All chromosomes participate in mitosis and meiosis. Two of the chromosomes are called “sex chromosomes” and are involved in gender determination. The remaining chromosomes are called autosomes. Chromosome (Cytogenetic) studies are described further in Chapter 17.
Mitosis
When body cells divide, the chromosomes first replicate, then condense by tight coiling (as already described) to become the discrete chromosome elements shown in a karyotype. At cell partition, the duplicated strands separate so that each daughter cell has an exact replica of the genetic material of the original cell. This process assures that all cells of the body are genetically identical and have the normal chromosome number (the diploid number). For domestic horses, this diploid chromosome number is 64, a collection of 32 pairs of chromosomes. One chromosome of each pair has a maternal origin, the other a paternal origin.
Meiosis
Meiosis generates gametes (sperm in males and ova in females) with only 32 chromosomes (the haploid number)—only one copy from each of the chromosome pairs found in normal diploid cells. When a sperm and an ovum combine during fertilization to form a zygote, the chromosome number in the resulting cell is 64, reconstituting the diploid chromosome number and gene composition appropriate for the animal we know as the horse.
Integral to meiosis are two aspects directly responsible for the characteristics of gene inheritance.
• Reduction division, which results in the gamete receiving only one chromosome of each pair. Thus, chromosomes derived from each parent are randomly distributed through the children and on to the grandchildren. This process reassorts chromosome pairs in each generation and generates characteristic trait ratios and segregation of alleles. Mendel did not know about chromosomes, but he hypothesized this kind of process to explain inheritance.
• Recombination, which allows homologous maternal- and paternal-derived chromosomes to exchange sections. This crossing-over process was not part of the genetic theory hypothesized by Mendel but is the basis for the important concept of linkage genetics.
An animal has only two copies of each gene despite the genetic input from many pedigree elements. For example, all four grandparents will provide material to the overall genetic makeup of a grandchild, although for each specific gene only two grandparents, one from the paternal side and one from the maternal side, will be represented. Certain groups of genes are likely to be co-contributed because genes are closely strung together on linear chromosomes. Meiosis ensures that genes on different chromosomes, or far apart on one chromosome, are unlikely to stay together beyond a few generations.
This summary of the cell division processes is by necessity brief. Consult a basic text on genetics for a more detailed review. For this topic, it would make very little difference for understanding the fundamental process whether a mouse, a fly, or a horse was the example. From the description of the various cell and chromosome division processes, and basic to all that follows, the key point to understand is that individual genes—the units of heredity—are passed on unaltered from parent to offspring, but the gene combinations are changed in every generation.
Linkage
Although the independent inheritance of genetic traits has been emphasized up to now, some genes will tend to be inherited together. The august monk Mendel did not envision the relationship that we now know to exist between genes and chromosomes. But to understand genetics more completely, it is necessary to expand his otherwise elegant theories to include gene linkage.
Any given gene has a particular chromosomal assignment and a place on that chromosome that we call a locus (plural: loci). Occasionally, traits of interest are on the same chromosome and tend to be inherited together more often than they are split apart: these are linked genes. Linked genes can be separated from each other as part of the normal process of chromosome recombination that occurs uniquely during meiosis. At present, the entire genome of the horse has been sequenced and we know the location and sequence of many genes of interest for the horse (Chapter 6 on horse genomics). Yet our understanding of the relationships between the bits of DNA and complex traits like behavior, performance, and many other phenotypic characteristics that we value in the horse remains to be developed.
The inheritance of gender
Two of a horse’s 64 chromosomes are called the sex chromosomes. The gender of a horse is the result of action by genes on the sex chromosomes. The sex chromosomes are designated X and Y. Females inherit two copies of the X chromosome. Males inherit an X chromosome and a Y chromosome. In mares, the two X chromosomes pair during meosis, undergo genetic recombination and each egg possesses one of the X chromosomes. During meiosis in the male, the X and Y chromosome pair and each sperm inherits either an X or Y chromosome. The pairing of the X and Y chromo some during meiosis seems exceptional because the X and Y chromosomes are quite different in size and gene content. However, they share DNA sequences for a very short region, called the pseudoautosomal region (PAR) and this is the basis for them to pair during meiosis. The genomics and cytogenetics of X and Y chromosomes are discussed further in Chapters 6and 17.
The consequences of sexual reproduction are that the gender of a foal is determined by the contribution from the sire, not the dam. The dam always contributes an X chromosome to her offspring. The sire contributes sperm with either X or Y. As a consequence, the sex of the offspring is determined by the contribution of the sire—specifically, whether he contributes an X or Y chromosome.
References
Adzhubei, I.A., Schmidt, S., Peshkin, L. et al. (2010) A method and server for predicting damaging missense mutations. Nature Methods 7: 248–29.
Avery, O.MacLeod, C. and McCarty, M. (1944) Studies on the chemical nature
