Evolution of siglec-11 and siglec-16 genes in hominins

Xiaoxia Wang, Nivedita Mitra, Pedro Cruz, Liwen Deng, Nissi Varki, Takashi Angata, Eric D. Green, Jim Mullikin, Toshiyuki Hayakawa, Ajit Varki

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We previously reported a human-specific gene conversion of SIGLEC11 by an adjacent paralogous pseudogene (SIGLEC16P), generating a uniquely human form of the Siglec-11 protein, which is expressed in the human brain. Here, we show that Siglec-11 is expressed exclusively in microglia in all human brains studied -a finding of potential relevance to brain evolution, as microglia modulate neuronal survival, and Siglec-11 recruits SHP-1, a tyrosine phosphatase that modulates microglial biology. Following the recent finding of a functional SIGLEC16 allele in human populations, further analysis of the human SIGLEC11 and SIGLEC16/P sequences revealed an unusual series of gene conversion events between two loci. Two tandem and likely simultaneous gene conversions occurred from SIGLEC16P to SIGLEC11 with a potentially deleterious intervening short segment happening to be excluded. One of the conversion events also changed the 5′ untranslated sequence, altering predicted transcription factor binding sites. Both of the gene conversions have been dated to ∼1-1.2 Ma, after the emergence of the genus Homo, but prior to the emergence of the common ancestor of Denisovans and modern humans about 800,000 years ago, thus suggesting involvement in later stages of hominin brain evolution. In keeping with this, recombinant soluble Siglec-11 binds ligands in the human brain. We also address a second-round more recent gene conversion from SIGLEC11 to SIGLEC16, with the latter showing an allele frequency of ∼0.1-0.3 in a worldwide population study. Initial pseudogenization of SIGLEC16 was estimated to occur at least 3 Ma, which thus preceded the gene conversion of SIGLEC11 by SIGLEC16P. As gene conversion usually disrupts the converted gene, the fact that ORFs of hSIGLEC11 and hSIGLEC16 have been maintained after an unusual series of very complex gene conversion events suggests that these events may have been subject to hominin-specific selection forces.

Original languageEnglish
Pages (from-to)2073-2086
Number of pages14
JournalMolecular Biology and Evolution
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 1 2012
Externally publishedYes

Fingerprint

Sialic Acid Binding Immunoglobulin-like Lectins
Gene Conversion
gene conversion
Hominidae
gene
brain
Genes
genes
Brain
neuroglia
Microglia
Non-Receptor Type 6 Protein Tyrosine Phosphatase
allele
Pseudogenes
pseudogenes
Homo
Gene Frequency
human population
common ancestry
Population

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Wang, X., Mitra, N., Cruz, P., Deng, L., Varki, N., Angata, T., ... Varki, A. (2012). Evolution of siglec-11 and siglec-16 genes in hominins. Molecular Biology and Evolution, 29(8), 2073-2086. https://doi.org/10.1093/molbev/mss077

Evolution of siglec-11 and siglec-16 genes in hominins. / Wang, Xiaoxia; Mitra, Nivedita; Cruz, Pedro; Deng, Liwen; Varki, Nissi; Angata, Takashi; Green, Eric D.; Mullikin, Jim; Hayakawa, Toshiyuki; Varki, Ajit.

In: Molecular Biology and Evolution, Vol. 29, No. 8, 01.08.2012, p. 2073-2086.

Research output: Contribution to journalArticle

Wang, X, Mitra, N, Cruz, P, Deng, L, Varki, N, Angata, T, Green, ED, Mullikin, J, Hayakawa, T & Varki, A 2012, 'Evolution of siglec-11 and siglec-16 genes in hominins', Molecular Biology and Evolution, vol. 29, no. 8, pp. 2073-2086. https://doi.org/10.1093/molbev/mss077
Wang X, Mitra N, Cruz P, Deng L, Varki N, Angata T et al. Evolution of siglec-11 and siglec-16 genes in hominins. Molecular Biology and Evolution. 2012 Aug 1;29(8):2073-2086. https://doi.org/10.1093/molbev/mss077
Wang, Xiaoxia ; Mitra, Nivedita ; Cruz, Pedro ; Deng, Liwen ; Varki, Nissi ; Angata, Takashi ; Green, Eric D. ; Mullikin, Jim ; Hayakawa, Toshiyuki ; Varki, Ajit. / Evolution of siglec-11 and siglec-16 genes in hominins. In: Molecular Biology and Evolution. 2012 ; Vol. 29, No. 8. pp. 2073-2086.
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