How Chromosomes Cheat

Cheating is wrong and something that we, as humans, should avoid: it’s unfair. Though for some chromosomes this is just in their nature.

Recently a team from the University of Pennsylvania conducted a study entitled “Spindle asymmetry drives non-Mendelian chromosome segregation” (http://science.sciencemag.org/content/358/6363/668 ). This basically means that they discovered how chromosomes “cheat” to have a rate of making it into the functional ovum, as opposed to a polar body, which is much higher than chance would predict (a polar body being one of three smaller cells that buds off from an oocyte, a cell in the ovary which undergoes meiosis to form an ovum, at the oocyte’s two meiotic divisions and degrades as opposed to developing into an ovum). This process in which certain alleles are favourably transmitted to the gamete is known as “meiotic drive”.

Spindle asymmetry drives non-Mendelian chromosome segregation Source | https://www.genengnews.com/gen-news-highlights/cheating-chromosomes-vault-past-competitors-to-reach-egg-cell-first/81255126 [University of Pennsylvania]

Spindle asymmetry drives non-Mendelian chromosome segregation

Source | https://www.genengnews.com/gen-news-highlights/cheating-chromosomes-vault-past-competitors-to-reach-egg-cell-first/81255126 [University of Pennsylvania]

The study involving mouse oocytes detected molecular signals which were shown to create an asymmetry in the machinery driving meiosis. To investigate the cause of this, the researchers focused on the meiotic spindle: the structure which pulls the pair of chromosomes apart to opposite poles of the cell by their centromere during anaphase I and later pulls the sister chromatids apart to opposite poles of the cell during anaphase II (anaphase I and II being stages during meiosis). The team looked at microtubules, which the meiotic spindle consists of, and found a lower distribution of a modification called tyrosination in the egg side of the cell as opposed to the opposite side, the cortex. However, this asymmetry in the distribution of tyrosination was only present during the stage of meiosis when the spindle moves from the equator, the middle of the cell, towards the cortex. This therefore shows that the cortex is the origin of the signal which sets up the modification of tyrosine.

With this established the researchers then tested their hypothesis of whether a molecule called CDC42, Cell Division Control Protein 42 homolog, contributed to tyrosination being asymmetrical. Members of the team, Lampson and Chenoweth, created an experimental system to test this by using a light-sensitive assay (an investigative procedure to determine the functional activity of CDC42) to selectively enrich CDC42 on one side of the pole (the signals shown as green in the diagram with the microtubule tyrosination in white). From this they inferred that CDC42 was at least partly responsible for inducing the tyrosination asymmetry and so the spindle’s asymmetry in the dividing cell.

Meiotic Drive | Source ~ http://web.sas.upenn.edu/lampson-lab/research/cell-biology-of-meiotic-drive/

Meiotic Drive | Source ~ http://web.sas.upenn.edu/lampson-lab/research/cell-biology-of-meiotic-drive/

Now- bear with me I’m almost there- having now discovered that the asymmetry exists and how it is caused, they then focused on how chromosomes can “cheat” as a result of this”.  They did so by comparing the effect of having larger, “stronger” centromeres or smaller, “weaker” centromeres during meiosis. With the use of live imaging of mouse oocytes they were able to discover that “stronger” centromeres were more likely to detach themselves from the spindle, especially when orientated to the cortical side of the cell, than the weaker ones which didn’t really seem to mind being in either side of the cell. They believe that the stronger ones do so in order flip themselves so that they are they are positioned to the pole of the cell which will later develop into the ovum ( see diagram) as “if you’re a selfish centromere and you’re facing the wrong way… that’s how you win”, as said by Lampson.

Whilst Lampson and his team’s work has shed more light into the segregation of chromosomes to gametes, and so helped further the understanding of certain conditions like Down’s syndrome where there are errors in this, there are still “ a ton” of other questions, like how “centromeres evolve to win these competitions” Lampson has said. Questions which explore why we are who we are:  questions which Lampson and his team hope to later investigate.

So there you have it. The combination of chromosomes we received from our parents may not be so random after all; thanks to how some chromosomes “cheat” to influence this process… or rather “make better use of circumstances than others”, some may prefer to say.