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While chromosome 19 only is the 19th largest autosomal chromosome, it contains 1440 protein-coding genes, and thus has the second highest number of protein-coding genes of any human chromosome.

For comparison: If one would naively assume the same density of protein-coding genes as on chr1, which has the highest absolute number of protein coding genes (2109), the anticipation for chr19 would be ~540 protein-coding genes.

The x-axis of this graph highlights the increased density of protein-coding genes on chromosome 19; The x-axis highlights the increased density of genes on Chromosome 19.

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    $\begingroup$ I don't think there is any answer to "why". $\endgroup$
    – WYSIWYG
    Commented Jul 18, 2016 at 11:19
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    $\begingroup$ Within any natural population there are going to be outliers. The distribution graph you show has a long tail, which is to be expected. Look for graphs on the distribution of height, for example, and you'll see that 90% of the values are within a fairly small range, but the 5% on either side stretch out quite far, as there are extreme outliers on both ends. $\endgroup$
    – MattDMo
    Commented Jul 18, 2016 at 13:31
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    $\begingroup$ As extreme outliers in natural populations often are somehow special, and as a n of over 1000 genes would strongly argue against as many independent chance events, I was curious if there is something special about chr 19 or its genes, which could favor such a comparatively high gene density. $\endgroup$
    – tsttst
    Commented Jul 18, 2016 at 14:02
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    $\begingroup$ I think that OP is correct that there is something to explain here (i.e., the standard null models for gene distribution across the genome would not predict such an outlier), but I think that nobody knows the answer. $\endgroup$
    – Daniel Weissman
    Commented Jul 21, 2016 at 16:15
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    $\begingroup$ @WYSIWYG I think "why" in this case translates to "what events led to". $\endgroup$
    – James
    Commented Jul 27, 2016 at 4:25

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This Nature paper from 2004, by Jane Grimwood et al. goes at least a long way towards giving an answer to the question of the OP. In short: there were inordinately many duplications, especially during an event 30-40 million years ago, as well as during a much more recent event. These duplications are, uncharacteristically, predominantly intra-chromosomal rather than inter-chromosomal. Also, chromosome 19 contains a lot of immunoglobin-like paralogues: a type of gene for which it is clearly evolutionarily adaptive to undergo rapid duplication followed by random mutation, as they play a role in adapting to potential antigens.

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It's interesting that not only the leader 19, but also 16 and 17 follow a similar trend. Perhaps their size could be the best weight/length proportion to ensure a safe replication? Then what would have to be explained would be 18, so far to the left. That could be if 18 is newer, resulting from the split of a larger chromosome or the fusion of two smaller, having yet no time to accumulate a greater number of genes favoured by the advantages of the "genes positional co-evolution" (if such thing exists).

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