Why does human chromosome 19 have the second highest number of protein-coding genes? 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.](

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.