Wednesday, November 08, 2017

How much mitochondrial DNA in your genome?

Most mitochondrial genes have been transferred from the ancestral mitochondrial genome to the nuclear genome over the course of 1-2 billion years of evollution. They are no longer present in mitochondria but they are easily recognized because they resemble α-proteobacterial sequences more than the other nuclear genes [see Endosymbiotic Theory].

This process of incorporating mitochondrial DNA into the nuclear genome continues to this day. The latest human reference genome has about 600 examples of nuclear sequences of mitochondrial origin (= numts). Some of them are quite recent while others date back almost 70 million years—the limit of resolution for junk DNA [see Mitochondria are invading your genome!].

Estimating the number of numts isn't as easy as you might imagine. There are two main problems according to Hazkani-Covo and Martin (2017).
  1. Simple BLAST searches using mitochondrial sequences against the nuclear genome may overestimate the number of insertion events. That's because the hits need to be concatenated to see the extent of the insertion. You also need to take into account subsequent events, such as the insertion of a transposon into the mitochondrial fragment, that makes a single insertion event look like two independent events in genomic analyses.
  2. The number of numts may be underestimated because mitochondrial sequences are usually thought to be contaminants and they are removed from the genome sequence. There are several documented cases.
The authors examined 36 genomes for the presence of mitochondrial DNA. They looked at each potential event separately to verify that it was a genuine numt. They also looked for nupts—plastid DNA—in 24 genomes.

The results vary from a low of 7 numts to 6550 numts depending on the size of the genome. The best estimates for humans is 592, which is pretty much in line with earlier results. The number of nupts in plants and algae is about the same.


Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 175 [Pearson: Principles of Biochemistry 5/E]

Hazkani-Covo, E., and Martin, W.F. (2017) Quantifying the number of independent organelle DNA insertions in genome evolution and human health. Genome Biology and Evolution, evx078. [doi: 10.1093/gbe/evx078]

30 comments:

  1. On the other end, what's the most recent deletion of a gene from any mitochondrial genome, i.e. what's the most recent transfer, and in what taxon?

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  2. Off the top of my head, and confined within animals;

    - Some cheatognaths have lost the tRNAs (except for the f-MET which is retained), and ATP 8 and 6. I am not sure if ATP6 has been found in the nuc-DNA. tRNAs are most likely lost (not transferred), but there is a bioinformatic (experiment-free) paper claiming to see cryptic tRNAs.
    http://www.pnas.org/content/101/29/10639.long
    http://www.sciencedirect.com/science/article/pii/S147692711530236X?via%3Dihub

    -Some nematodes (such as C. elegans) and some flatworms are lacking atp8, but the gene has not been found in the nucleus. This is probably a loss, and not a "move".

    - some cnideria also appear to have lost the tRNAs, but there are non-coding regions and the possibility of cryptic tRNA sequences that are post-transcriptionally modified.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633667/

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    1. Off the top of my head and based on stuff I looked up many years ago I thought all animals had 13 protein coding genes except for flatworms, which had 12

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    2. Interesting review of animal mtDNA variation, including gene content, here:

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633667/

      I was interested to discover that lots of animals have mt genomes that are other than a single circular chromosome. I had known that some cnidarians have linear mt genomes, but had never heard of multiple circular chromosomes.

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  3. Are there are any negative repercussions or potential benefits for these transfers?

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  4. @Micheal Okoko,
    ... sorry I don't get a window when I click on reply.

    Quoting from https://doi.org/10.1371/journal.pgen.1000834


    "Integration of numts not only appears as neutral polymorphism but, more rarely, is also associated with human diseases [32]; five cases are currently known (Figure 2). One involved a 41-bp mtDNA insertion at the breakpoint junction of a reciprocal translocation between chromosome 9 and 11 [33], the remaining cases involve insertion of mtDNA into genes. A splice site mutation in the human gene for plasma factor VII that causes severe plasma factor VII deficiency (bleeding disease) results from a 251-bp numt insertion [34]. A rare case of Pallister-Hall syndrome in which a 72-bp numt insertion into exon 14 of the GLI3 gene causes a premature stop codon, is associated with Chernobyl [35]. A case of mucolipidosis IV in which a 93-bp segment was inserted into exon 2 of MCOLN1, eliminated proper splicing of the gene [36]. As the last known example, a 36-bp insertion in exon 9 of the USH1C gene associated with Usher syndrome type IC [37] is a numt [32]. As in other cases of numt insertions, the mitochondrial genome remains intact in the afflicted individuals."

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  5. Incidentally, numts can be a big problem for those interested in sequencing mtDNA, especially if you get your extracts from tissues deficient in mitochondria. For example, I was never able to get any real mitochondrial sequence for the spur-winged goose Plectropterus gambensis, but I did get three very nice numts that, fortunately, are all more closely related to each other than to the mt sequence of any other species and thus make reasonable proxies for mt sequence. One might even consider them better, because they turn one taxon sample into three and break up a potential long branch.

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    1. I really suggest reading this paper,
      http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000834

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    2. Ugh... I meant that comment to be a general one, not a reply to you. No more commenting from my phone... Apologies.

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  6. I'm assuming that most of the numts discussed above are
    non-functional mitochondrial fragments. I'll bet a quick check of ENCODE would show RNAs produced from these loci. This would be a specific refutation of the claim for most/all lcRNAs being functional.

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    1. Nah, that would just be used as evidence that numts are functional. You know, like all the rest of the "junk" DNA.

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  7. "Most mitochondrial genes have been transferred from the ancestral mitochondrial genome to the nuclear genome over the course of 1-2 billion years of evollution"

    im not sure prof moran:

    https://www.ncbi.nlm.nih.gov/pubmed/25848019

    " A surprising result of phylogenetic analyses is the relatively small proportion (10-20%) of the mitochondrial proteome displaying a clear α-proteobacterial ancestry."

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    1. The article dcs... references has nothing at all to do with the statement "Most mitochondrial genes have been transferred from the ancestral mitochondrial genome to the nuclear genome over the course of 1-2 billion years of evolution."

      The article reports that a larger-than-expected number of proteins found in the mitochondria are coded for by eukaryote genes. (Note that proteins can be produced in the cell nucleus and then transferred into the mitochondria.)

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  8. bwilson:

    I think the article does much more than that, depending on what you mean by "eukaryote genes". It isn't about the current location of genes, whether in the mt or nuclear genome, but about their ultimate origins. By "eukaryote genes", the author doesn't mean genes located in the nucleus but genes that can't be traced to alpha-proteobacteria or any other eubacteria, i.e. that have homologs only in eukaryote nuclear genomes. The full article is available here.

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    1. Yes, I know. A lot of proteins in the mitochondria are coming from genes that come from lineages different from the one the mitochondria belong to. That's an interesting conclusion! Doesn't seem to support or refute the quote dscccc presented, about mitochondrial genes moving to the nucleus.

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    2. If the genes don't come from the mitochondrial symbiont at all, it does refute the claim. At least it would make the symbiont a very odd alpha-proteobacterium whose gene content didn't resemble those we currently have access to. I'm not quite sure what a reasonable scenario would be, but it certainly seems complicated.

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  9. dcsccc and John Harshman, you were right and I was wrong. I apologize. And I do wonder what's going on here!

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  10. bwilson, I'm sorry but I don't recognize the content of your comment. Nobody in my experience of Sandwalk has ever admitted being wrong about anything. I must assume that you mean something else.

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    1. (Smile) Just thought I'd introduce a new concept to the comments!

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    2. I don't think it will work. John never admits he's wrong! :-)

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    3. Larry,

      Make sure you don't insult John Harshamn's intelligence by comments like that... He is very sensitive about that...As you probably know...

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    4. Larry,

      I'm sorry. Off topic,

      Did you ban Dinogenes or has he/she/other passed away?

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    5. Can anyone confirm what happened to Dinogenes? If he has died, I hope not, can someone confirm his whereabouts?

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    6. Jass: "Did you ban Dinogenes or has he/she/other passed away?"

      1) I assume you mean Diogenes 2) He's fine and 3) He probably just bored of talking to creationist dropkicks on the internet. It does get pretty repetitive.

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  11. I just saw that this 2015 paper by Mike Grey on the evolution of the "mitochondrial proteome" is in PMC (so no paywall issues). It discusses some of the complication of the discussions that were going on here (lineage specific gene gains / loss, etc).

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547279/

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  12. We have not heard from Larry for quite some time. I hope all is well. Here is wishing a Happy New Year to Larry Moran and all present.

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    1. He seems to be OK. He's been posting pictures on Facebook of his grand kids playing in the snow, so I think it's just a matter of his having his priorities in order. :)

      Happy New Year to all Sandwalkers from me, as well!

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