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The role of copy number variations (CNVs) has been explained before. In 2006 I discussed the identification of 355 CNVs in the chimpanzee genome, later in 2007 a study fished out human lineage-specific CNVs by comparing them to ones found in chimpanzees, and lastly, this year, another study suggested that CNVs may account for much more genetic variation among individuals than we’ve previously thought. This week the journal Genome Research published a paper which is the largest comparison of CNV differences between human and chimpanzee genomes. The authors specifically sought to identifying regions that have been duplicated or lost during evolution of the two lineages.

Colocalization of CNVs and SDs in the human and chimpanzee genomes

Colocalization of CNVs and SDs in the human and chimpanzee genomes

The paper, “Copy number variation and evolution in humans and chimpanzees,” reports on using whole genome tilepath microarrays for the high-throughput identification of these chromosomal deletions and duplications. The arrays had 28,708 DNA clones on them and the DNA from 30 unrelated chimpanzees and 30 unrelated people of African ancestry were used in this comparative genomic screening. Why Africans? Well the  genetic diversity in Africans, especially sub-Saharan populations, is comparable to that of Western chimpanzees. In order compare large scale (kilobase) genetic variation, have populations that both exhibit inherit diversity already knocks out one variable.

DNA was isolated and hybridized to the arrays. Experiments were duplicated. CNVs were validated by FISH and PCR. The authors and reported that each individual had an average of 70 to 80 CNVs. CNVs of genes that genes involved in the inflammatory response and cell proliferation – are more commonly duplicated or deleted and also occur in both species very frequently in orthologous genomic regions, suggesting a tight association to homologous intrachromosomal segmental duplications. Some examples are APOL1, APOL4, CARD18, IL1F7, IL1F8 and are completely deleted from chimp genome. In humans, APOL1 is involved in immune response to the Trypanosoma brucei parasite, transmitted by the tsetse fly, that causes sleeping sickness. IL1F7 and CARD18 play a role in regulating inflammation: therefore, there must be different regulations of these processes in chimpanzees.

Of particular interest is the identification of a CNV: CCL3L1. When compared to chimpanzees, humans have far fewer copies of this gene. Deletions in CCL3L1 have been associated with increased susceptibility to HIV infection. Another gene, TBC1D3, involved in cell proliferation, was reduced in number in chimpanzee compared to human. On average, there were eight copies in humans sampled, but apparently only one in all chimpanzees and this difference. This difference is argued to have been driven by selection.

SNPs are usually the goto comparative genomic marker for most comparative genetic studies. In this situation CNVs were the star. CNVs can have more impactful phenotypic effects than SNPs — where a SNP may alter the shape a final protein makes or alter the promoter sequence, duplications of a gene can lead to more proteins produced. Deletions in copy numbers can also down size the amount of protein produce, affecting the biochemical pathways the product is involved in. So are CNVs more important thant SNPs or other forms of genetic variation? No. They are one of the many structural elements that need to be studied to completely understand the variomes present within human populations and between humans and related species.

    G. H. Perry, F. Yang, T. Marques-Bonet, C. Murphy, T. Fitzgerald, A. S. Lee, C. Hyland, A. C. Stone, M. E. Hurles, C. Tyler-Smith, E. E. Eichler, N. P. Carter, C. Lee, R. Redon (2008). Copy number variation and evolution in humans and chimpanzees Genome Research, 18 (11), 1698-1710 DOI: 10.1101/gr.082016.108