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Why do genes with closely related products are so often positioned on different chromosomes?

To illustrate what I mean, here is an example from immunology:

  • the invariant region of MHC is on chromosome 5
  • the variant region of MHC is on chromosome 6
  • β2-microglobulin is on chromosome 15

These three gene products associate into a single protein-complex to present antigens. Why are these genes situated on different chromosomes? Wouldn't it make more sense to keep them associated into a localized region onto a single chromosome so that their transcription can be jointly regulated?

It is just an example; I get the impression that many multiprotein complexes are formed with products from different chromosomes.

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    $\begingroup$ I don't understand your question - you mean why associated gene products are located on different chromosomes? $\endgroup$ – AliceD Apr 29 '15 at 1:21
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    $\begingroup$ probably, because it creates more variability, through random mutations and crosses you can enhance parts of same pathway independently. Chromosomes are mixed up during sexual reproduction as an additional mechanism of variability (together with crossing-over) during meiosis. $\endgroup$ – aaaaa says reinstate Monica Apr 29 '15 at 1:29
  • $\begingroup$ @AliceD Yes. Please edit my question if you think it needs clarification! My English is far from perfect. $\endgroup$ – inf3rno Apr 29 '15 at 3:08
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    $\begingroup$ Perhaps something like this? $\endgroup$ – AliceD Apr 29 '15 at 4:55
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    $\begingroup$ Simply because it can (happen). Natural selection does not yield processes that are designed because there are no designers involved. Barring non-terrestrial involvement (cf. the pan-spermian hypothesis), as Stephen Jay Gould was fond of pointing out, natural selection can only work on what has come before. In other words, the raw material consists of what is currently available (for better or worse). All that matters is having more offspring than other individuals have in the next generation. That is what gets selected. It doesn't matter what we think about comparative efficiency. $\endgroup$ – mdperry Apr 29 '15 at 11:01
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The thing we must remember is that during evolution, there occurs many events that may result in genomic reshuffling.

Considering your example of MHC, when we look into the evolution of the complexes

The classical human MHC contains 224 genes, .... Antibody and T cell mediated immune responses against invading pathogens are initiated through MHC class I and class II molecules. These main components are not only missing from invertebrates, but are also not present in primitive jawless fish, such as hagfish and lamprey. MHC class I and II molecules do, however, exist in all jawed vertebrates, including the cartilaginous fish.

Now that tells us something in itself. If you observe the universal evolutionary tree, we can conclude that the hagfish and lamprey are most ancestral, especially compared to telostii. This is crucial when speaking in terms of evolution, as

this demonstrates that the separation of the MHC class I and class II loci is characteristic of teleost fish, which represent half of all vertebrates. Since the genes of the immune system were present in the common ancestor of tetrapods and teleosts, the differences in their genomic organisation may be the result of lineage-specific chromosomal events such as duplications, inversions, deletions and translocations.

You can read more about the MHCs here:

Sambrook, Jennifer G., Felipe Figueroa, and Stephan Beck. "A genome-wide survey of Major Histocompatibility Complex (MHC) genes and their paralogues in zebrafish." BMC genomics 6.1 (2005): 152.

And thats usually the reason for the major changes you see. Often other changes occur, due to transposons, which cause pseudogenes to form and/or neofunctionaliation to occur. You can read about them here:

Feschotte, Cédric, and Ellen J. Pritham. "DNA transposons and the evolution of eukaryotic genomes." Annual review of genetics 41 (2007): 331.

I am fairly certain, that this applies practically to majority of the genes, that are not linked strongly genetically (http://learn.genetics.utah.edu/content/pigeons/geneticlinkage/).

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  • $\begingroup$ Can you give me some link about how this duplications, inversions, deletions and translocations affect the regulation of such genes? Are they activated by the same stimulus? I guess so, because they are duplicates at the beginning of separation. $\endgroup$ – inf3rno Apr 30 '15 at 15:17
  • $\begingroup$ Would you prefer me to answer here or in a different question? as you are asking more about functional divergence, and the evolutionary fate of diverged genes, and in the original question here you asked about linkage and genome wide chromosomal events $\endgroup$ – Rover Eye Apr 30 '15 at 15:29
  • $\begingroup$ If you think it does worth a new question, then ofc. I can write a new one. $\endgroup$ – inf3rno Apr 30 '15 at 15:31
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    $\begingroup$ @inf3rno its upto you really. You can look up subfunctionalisation here (en.wikipedia.org/wiki/Subfunctionalization) $\endgroup$ – Rover Eye Apr 30 '15 at 15:34
  • $\begingroup$ Thx, I'll read about it. $\endgroup$ – inf3rno Apr 30 '15 at 18:15

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