DUF1220 Domain Copy Number

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Human Uniqueness Compared to "Great Apes": 
Likely Difference
MOCA Domain: 

DUF1220 is a 65 amino acid protein domain that has undergone a striking human specific copy number expansion, resulting in the addition of over 80 new copies of the domain in humans compared to chimps. DUF1220 copy number increases as a function of a species' evolutionary proximity to humans with a trend of 28 copies being added every million years. The greatest number of copies (>270) is found in human while mice and rats have only 1 copy. DUF1220 sequences have also undergone recent positive selection and, while widely expressed, show high levels of expression in the fetal brain (Diskin et al. 2009) and in neurons (Popesco et al. 2006). The DUF1220 copy number in creases in humans involved both domain amplification and gene duplication (NBPF family), with the great majority of copies mapping to the 1q21.1 region. 1q21.1 CNVs that either flank or encompass DUF1220 domains have been implicated in a large number of diseases including microcephaly and macrocephaly (Brunetti-Pierri et al. 2008; Mefford et al. 2008), autism (Autism Genome Project Consortium 2008), schizophrenia (ISC 2008), heart disease (Mefford et al. 2008) and neuroblastoma (Diskin et al. 2009; Vandepoele et al. 2005). A model has been proposed linking the rapid increase in DUF1220 copy number with  the high number of disease-related CNVs in the 1q21.1 region (Dumas and Sikela 2009). The fact that the deletions and duplications of DUF1220-containing (or flanking) 1q21.1 sequences have been implicated in microcephaly and macrocephaly, respectively (Brunetti-Pierri et al. 2008; Mefford et al. 2008) has been used to support the view that DUF1220 copy number may be directly related to human brain size both within the human species as well as across human, primate, and mammalian evolution (Dumas and Sikela 2009). More recent worked has confirmed that DUF1220 copy number is associated with brain size pathology in pediatric populations (Dumas et al 2012).


Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Probable Appearance: 
6,000 thousand years ago
Definite Appearance: 
2,000 thousand years ago
The Human Difference: 

Types of Human-Specific Changes in DUF1220:

Accelerated Evolution

Copy Number Changes

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  1. DUF1220-domain copy number implicated in human brain-size pathology and evolution., Dumas, Laura J., O'Bleness Majesta S., Davis Jonathan M., C Dickens Michael, Anderson Nathan, Keeney J G., Jackson Jay, Sikela Megan, Raznahan Armin, Giedd Jay, et al. , Am J Hum Genet, 2012 Sep 7, Volume 91, Issue 3, p.444-54, (2012)
  2. Evolutionary history and genome organization of DUF1220 protein domains., O'Bleness, Majesta S., C Dickens Michael, Dumas Laura J., Kehrer-Sawatzki Hildegard, Wyckoff Gerald J., and Sikela James M. , G3 (Bethesda), 2012 Sep, Volume 2, Issue 9, p.977-86, (2012)
  3. Copy number variation at 1q21.1 associated with neuroblastoma, Diskin, Sharon J., Hou Cuiping, Glessner Joseph T., Attiyeh Edward F., Laudenslager Marci, Bosse Kristopher, Cole Kristina, Mosse Yael P., Wood Andrew, Lynch Jill E., et al. , Nature, 06/2009, Volume 459, Issue 7249, p.987 - 991, (2009)
  4. DUF1220 domains, cognitive disease, and human brain evolution., Dumas, L, and Sikela J M. , Cold Spring Harb Symp Quant Biol, 2009, Volume 74, p.375-82, (2009)
  5. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes., Mefford, Heather C., Sharp Andrew J., Baker Carl, Itsara Andy, Jiang Zhaoshi, Buysse Karen, Huang Shuwen, Maloney Viv K., Crolla John A., Baralle Diana, et al. , N Engl J Med, 2008 Oct 16, Volume 359, Issue 16, p.1685-99, (2008)
  6. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities., Brunetti-Pierri, Nicola, Berg Jonathan S., Scaglia Fernando, Belmont John, Bacino Carlos A., Sahoo Trilochan, Lalani Seema R., Graham Brett, Lee Brendan, Shinawi Marwan, et al. , Nat Genet, 12/2008, Volume 40, Issue 12, p.1466-71, (2008)
  7. Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains., Popesco, Magdalena C., Maclaren Erik J., Hopkins Janet, Dumas Laura, Cox Michael, Meltesen Lynne, McGavran Loris, Wyckoff Gerald J., and Sikela James M. , Science, 2006 Sep 1, Volume 313, Issue 5791, p.1304-7, (2006)
  8. A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution., Vandepoele, Karl, Van Roy Nadine, Staes Katrien, Speleman Frank, and van Roy Frans , Mol Biol Evol, 2005 Nov, Volume 22, Issue 11, p.2265-74, (2005)