Variation in chromosome number as »normal« state:
New evidence found in fish brain neurons

Günther Zupanc, Professor of Neurobiology at Jacobs University, and his co-workers at the Scripps Research Institute in La Jolla/California and the University of Leipzig for the first time provided evidence that even a profound deviation from the number of chromosomes typical for a species does not necessarily result in physiological or behavioural deficiencies of the organism. Analysis of newly generated neurons in the brains of the healthy adult knifefish showed, that approximately 80 % of the cells deviate from the “normal” number of 22 chromosomes with aberrations of up to 70 %. The study is published in the current online express issue of Developmental Neurobiology (2007: doi: 10.1002/dneu.20365)

[ Mar 30, 2007]  Established scientific doctrine for a long time has assumed that any cell of an organism contains identical genetic information encoded by a species-specific number of chromosomes, with the exception of sperms and eggs with half the number. Humans, for example, have a total of 46 chromosomes – 22 pairs of autosomal chromosomes and two sex chromosomes. Aberrations of this number were thought to usually result in severe diseases. Down syndrome, for example, which causes physical and mental disabilities in humans, is caused by three instead of two chromosomes No 21 in all cells of the body. Even if only part of the body’s cells exhibits this aberration, a phenomenon referred to as “mosaicism”, the severity of the symptoms is similar. The notion that an aberrant number of chromosomes is associated with severe defects of the organism has been reinforced by more recent studies which showed that most, if not all, tumor cells exhibit marked variations in chromosome number among their cells.

Günther Zupanc, together with his research group at Jacobs University, as well as the groups of Jerold Chun in La Jolla and Andreas Lösche in Leipzig, now provided evidence that the neurons in the brains of the brown ghost knifefish Apteronotus leptorhynchus are a genetic mosaic in terms of chromosome numbers. Like other teleost fish, this species is distinguished by its enormous potential to continuously produce new neurons in the adult brain. By studying stained microscopic preparations of neuronal cells, the researchers found that only 20 % of the “newborn” cells have the typical set of chromosomes characteristic of this species, 22 chromosomes. Most of the other cells have less, whereas some have more. In many of the cells, the chromosome number differs quite dramatically from the most common number of 22, with up to 16 chromosomes being lost and up to 12 chromosomes gained. These variations were not accompanied by any kinds of deficiencies but appeared to be normal in healthy fishes.

The analysis of dividing cell samples proved segregation defects during mitotic cell division to be the cause for these aberrations in chromosome number: Instead of a symmetrical cell division resulting in two daughter cells with equal number of chromosomes, asymmetrical cell divisions occurred with daughter cells differing in chromosome numbers.

Günther Zupanc about the implications of the study: “The results of our research suggest that the loss or gain of chromosomes provides a novel mechanism to regulate gene expression during the normal development of some organisms”, he says. “Cells that contain more than two copies of a given chromosome will presumably produce more of a functional protein encoded by the gene located on this chromosome, cells that contain less than the normal chromosome pair are likely to produce less, thereby resulting in a variation of the same piece of genetic information.” The results of the study will be important to better understand the variability of normal developmental mechanisms in organisms, the neurobiologist from Jacobs University continues. “But we might also be able to learn more about the role of aberrant chromosome numbers in processes involved in certain diseases, such as the formation of tumors”, he concludes.