Y chromosome: The price you pay when you do not buy.

The current issue of the Science publishes three papers (http://www.sciencemag.org/content/343/6170/536.abstract; http://www.sciencemag.org/content/343/6170/541.abstract;


) that discuss the exposure of the opposite sex on life span or aging. In C. elegans, not only the copulation but also the exposure of hermaphrodites to medium in which males were once present can induce shortening of the life span of hermaphrodites. The same observation was made independently in Drosophila in which female-produced pheromones have negative effect on longevity of males.

It looks interesting to me because C. elegans has no Y chromosome whereas Drosophila has. Both organisms balanced the expression of sex chromosome linked genes by the dosage compensation mechanism. In C. elegans, the rate of transcription is down regulated from both X chromosomes in hermaphrodites. In male Drosophila, the rate of transcription increases by two folds for the X chromosome. This is needed because there are no or few active genes on the Y chromosome due to degeneration. This makes us to think that one day we will be with out the Y chromosome like C. elegans.  However, these recently published papers forced me to think a putative link between the Y chromosome and longevity. It might be that the presence of the Y chromosome makes female more selective for masculine characters. Killing of males with the Y chromosome allows female to restrict the male-defining genes in a small group that are selected to mate in next generation. Similarly, in the absence of the Y chromosome, killing of hermaphrodite allows to restrict the superior female genes in a small group that will be selected for contributing to next generation. In the absence of the Y chromosome, even the environment becomes a killer.

Sex chromosome evolution: A model that explains why we cannot eradicate poverty.

Today I read the prediction made by Bill Gates that there would be no poor country after 2035. Although I have been reading such statements, I never thought as deeply as I thought after reading Bill’s prediction. Even if I am a socialist, I realized that we couldn’t eradicate poverty completely.   The simple logic I have is based on my knowledge of dosage compensation in heterogametic organisms like human. It might be that I am wrong, as I am not an economist. However, I think the evolution of sex chromosome can be a good model to understand the existence of poverty and how to balance it rather than eradicating it.

In any organisms which sex is determined by a divergent chromosome pair (X and Y), there is an imbalance in gene dosage between sexes. Female contains two copy of X chromosome where as male contains only one copy of X chromosome and one copy of Y chromosome. This imbalance creates a problem during early development and thus nature has evolved a compensatory mechanism to overcome this problem. This is called as dosage compensation. This causes either inactivation of one copy of X-chromosome in female (as in human) or increase the rate of transcription of X-linked genes by two fold in male as in fly. The dosage compensation is coupled with degeneration of Y chromosome that is sex-limited.

This sex-limitation of Y chromosome greatly reduced their proportion in population, and therefore; for every pair of male and female, there is only one Y chromosome  (minor chromosome) for three X chromosomes. The ratio of minor and major chromosome can be maintained either by altering the proportion of males and females that contribute for the next generation or by increasing the rate of success of one sex compared to the other. In human male is heterogametic, and this explains that polygamy nature of male is selected by nature. Polygamy male helps to keep the Y chromosome in the population as each Y chromosome are different due to lack of recombination and degeneration of Y chromosome. If a female mate more than one male, it might affect the fitness of all male due to a recessive mutation on X chromosome and it will also reduce the diversity of female population.

Due to degeneration, there is gene loss from Y chromosome due to integration of repetitive DNA elements. For example, Y chromosome in human codes for 27 male-specific protein compare to >1,000 found on X chromosome. Along with lack of recombination and genetic drift, gene loss act to degrade Y chromosome. This suggests that Y chromosome can degenerate to the point of its disappearance from the population. Many researches support this hypothesis by referring the lack of Y chromosome in many other organisms like C. elegans. However, the rate of loss of gene appears to be asymptotic rather than linear. It explains that the rate of gene loss from Y chromosome gets slower as the time progress. The younger the Y chromosome, the higher the rate of gene loss would be. This is equivalent to the enzymatic reaction where we never get the 100 % saturation or Vmax irrespective of amount of substrate or enzyme. If we consider Vmax or disappearance of Y chromosome as a time when every one will be equally rich and equally poor, we will reach there after infinite time. My point is we will never achieve that and thus some part of this world will be still poor at any time of measurement. That stage will be disaster. It is good to have few very rich people than few very poor people. First condition will keep the society in equilibrium (conservation of torque in Physics). On the basis of this theory, I think that it is impossible to eradicate poverty completely.  In other words, very few people will be selected to be rich like mating and thus majority will be poor (According to the theory that nature selects few to contribute in the next generation). The question arises then what would be the solution. In my opinion, the solution is the evolution of Y chromosome i.e., strong selection for genes (quality) residing on Y chromosome (the poor). Similarly, if we change our society in such a way that people from resources poor area must be selected at any given time for contributing in the development of society. In that case, even if there is no distribution of resources equally (equivalent to no crossing over), both poor and rich will complement each other to develop society (equivalent to mating of X and Y chromosome to form the next generation).

Thus, the rich and the poor are equivalent to X and Y chromosome, and they are complementary to each other. This similarity suggests us that we should either reduce the number of involvement of rich people (limit their activity for fewer things) or make the poor to decide the most important decision of the society. On the basis of dosage compensation in fly, we should try to increase the number of resources or activity in the poor are i.e., to involve them in multiple things. This will make the society multimodal (equivalent to Y chromosome polygamy) with respect to utilization of resources. Now, society looks like having a single mode (monogamy) i.e., fewer people utilize most of the resources.

Polygamy is a solution for eradication of poverty.

Sex chromosome is more interesting than sex.

I chose M. Sc. over MBA because I was interested in sex (evolution!!!!!). During my master, it always puzzled me why there is X-chromosome inactivation in female. It left an impression in my mind that inactivation of X-chromosome is a universal mechanism for dosage compensation in species that have two X-chromosomes in one sex. It taught me that nature want to equalize male and female. But this idea got changed last week when I came to know that Drosophila has different mechanism for the dosage compensation. It occurs in male Drosophila instead of female. The X chromosome is specifically targeted by male specific lethal (MSL)-complex that increases the transcription of X-linked genes by two-fold. MSL-complex is absent in female. This forced me to think that even evolution is biased for male in human. The first simple logic is that the ratio of expression of Y-linked genes to X-linked genes in human and Drosophila. Since Drosophila has two fold increment for X-linked genes, the ratio is ½ in male fly whereas it is just 1/1 in human male. The Y chromosome contains genes related to masculinity whereas X-chromosome contains genes for feminity. So nature favors more expression of female related genes in lower organism than human. Is this the really reason that human have the X-chromosome inactivation in female than two- fold increment in male like fly. The second reason could be cancer (it came in my mind because my father died due to cancer). It might be that X-chromosome contains proto-oncogenes. I found that one proto-oncogene (ARAF1) of 98 oncogenes is on  X-chromosome in human. This looks simple and straightforward that to control the expression of the ARAF1 below the threshold level, nature opted for the X-chromosome inactivation than two-fold increment of X-linked genes in male. This might be true if there is no other oncogene on X-chromosome but we cannot tell confidently. Moreover, it is puzzling to me that why nature selects the ARAF1 on X-chromosome than autosome. Will the ARAF1 not be active on autosome?  Will it be more frequently oncogenic when resides on autosome than X-chromosome? Therefore, I think that there are more uncharacterized oncogenic genes on X-chromosome or the chance of converting oncogene from proto-oncogene is less when the gene is regulated on X-chromosome (seems odd due to lack of recombination between sex chromosomes, there is more chance of accumulation of mutation on X-chromosme). Whatever the reason, but it also suggests that nature wants to protect male from cancer due to higher expression of oncogenes on X-chromosome.

Therefore, it looks to me that nature is gender bias at least in the case of human. I have been reading many articles that nature favors X-chromosome as there is disintegration of Y-chromosome, people predict that this erosion might cause complete loss of Y-chromosome and genes related to masculinity. Now, I think just reverse of this that nature selected X-chromosome for oncogenes and make Y-chromosome free of oncogenes. In other words, there are no oncogenes on Y-chromosome but there is at least one oncogene in X-chromosome, which makes X-chromosome oncogenic.It will be interesting to test in lower organism for enrichment of cell division genes on sex chromosome or on the mating type chromosome.

One of the hypotheses of sex chromosome evolution is lack of recombination between two homologous chromosomes. Lack of recombination causes accumulation of mutations, which is coupled with dosage compensation on X-chromosome and disintegration of Y-chromosome linked genes. Therefore, people believe that lack of crossing over leads the evolution of sex chromosome. Further, differentiation of sex chromosome from homologous pair of autosome select dosage compensation machinery. Identification of binding site of MSL complex in D. Miranda would be useful to test whether increasing of expression of genes by two-fold on one autosome will lead to the evolution of sex chromosome from this autosomes. This would tell whether dosage compensation is coupled with sex chromosome evolution as the lack of recombination is.  The other hypothesis that disintegration of Y-chromosome linked genes causes dosages compensation is not true at least in Drosophila.

Finally, It still left me thinking whether evolution of cancer genes is coupled with sex evolution. Thus, understanding sex chromosomes are always more fascinating than understanding the opposite sex.