Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms

Angata, Takashi; Margulies, Elliott H.; Green, Eric D.; Varki, Ajit

doi:10.1073/pnas.0404833101

Cited by 153 publications

(162 citation statements)

References 36 publications

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“…While the number of indel differences between human and chimpanzee genomes is lower than the number of Single Nucleotide Divergences (SNDs), fixation of such events could suggest that these losses/gains have been adaptive. There are already a few known examples of indels with potential functional consequences differentiating humans and chimpanzees (Table 3), including the human loss of CMAH gene function in humans due to a 92-bp exon deletion (Chou et al 1998); the loss of two coding exons in the human ELN gene, which contributes to extracellular matrix structure (Szabo et al 1999), and the complete deletion of SIGLEC13 in humans (Angata et al 2004).…”

Section: Examine Sites Of Human-specific Insertions and Deletionsmentioning

confidence: 99%

Comparing the human and chimpanzee genomes: Searching for needles in a haystack

Varki

Altheide²

2005

Genome Res.

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The chimpanzee genome sequence is a long-awaited milestone, providing opportunities to explore primate evolution and genetic contributions to human physiology and disease. Humans and chimpanzees shared a common ancestor ∼5-7 million years ago (Mya). The difference between the two genomes is actually not ∼1%, but ∼4%-comprising ∼35 million single nucleotide differences and ∼90 Mb of insertions and deletions. The challenge is to identify the many evolutionarily, physiologically, and biomedically important differences scattered throughout these genomes while integrating these data with emerging knowledge about the corresponding "phenomes" and the relevant environmental influences. It is logical to tackle the genetic aspects via both genome-wide analyses and candidate gene studies. Genome-wide surveys could eliminate the majority of genomic sequence differences from consideration, while simultaneously identifying potential targets of opportunity. Meanwhile, candidate gene approaches can be based on such genomic surveys, on genes that may contribute to known differences in phenotypes or disease incidence/severity, or on mutations in the human population that impact unique aspects of the human condition. These two approaches will intersect at many levels and should be considered complementary. We also cite some known genetic differences between humans and great apes, realizing that these likely represent only the tip of the iceberg.Humans (Homo sapiens) and chimpanzees (Pan troglodytes) last shared a common ancestor ∼5-7 million years ago (Mya) (Chen and Li 2001;Brunet et al. 2002). What makes humans different from their closest evolutionary relatives, and how, why, and when did these changes occur? These are fascinating questions, and a major challenge is to explain how genomic differences contributed to this process

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Section: Examine Sites Of Human-specific Insertions and Deletionsmentioning

confidence: 99%

Comparing the human and chimpanzee genomes: Searching for needles in a haystack

Varki

Altheide²

2005

Genome Res.

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289

221

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“…1,2 More than a dozen human Siglecs are reported, of which Siglec-3 and Siglecs-5 through -11 are classified into a subgroup named CD33-related Siglecs (CD33rSiglecs), which are rapidly evolving. [1][2][3][4] Although each CD33rSiglec has unique expression profile, they are predominantly found on leukocytes involved in innate immunity.…”

Section: Introductionmentioning

confidence: 99%

Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils

Zhang

Angata

Cho

et al. 2007

Blood

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CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4+ cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F–null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti–Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders.

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“…The CD33-related siglecs are a distinct subset, which are expressed predominantly by cells of the innate immune system and appear to be undergoing rapid and continuous evolution [3] ( Table 1). In humans, there are eight CD33-related siglecs, all of which contain two conserved, tyrosine-based signaling motifs, comprising a membrane proximal ITIM and an ITIM-like motif.…”

Section: Introductionmentioning

confidence: 99%