Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2010 Oct;27(10):2333-43.
doi: 10.1093/molbev/msq118. Epub 2010 May 9.

Comparative genomics and evolution of the alpha-defensin multigene family in primates

Affiliations
Comparative Study

Comparative genomics and evolution of the alpha-defensin multigene family in primates

Sabyasachi Das et al. Mol Biol Evol. 2010 Oct.

Abstract

Defensin genes encode small cationic antimicrobial peptides that form an important part of the innate immune system. They are divided into three families, alpha (α), beta (β), and theta (), according to arrangement of the disulfide bonding pattern between cysteine residues. Considering the functional importance of defensins, investigators have studied the evolution and the genomic organization of defensin genes. However, these studies have been restricted mainly to β-defensins. To understand the evolutionary dynamics of α-defensin genes among primates, we identified the α-defensin repertoires in human, chimpanzee, orangutan, macaque, and marmoset. The α-defensin genes in primates can be classified into three phylogenetic classes (class I, II, and III). The presence of all three classes in the marmoset indicates that their divergence occurred before the separation of New World and Old World monkeys. Comparative analysis of the α-defensin genomic clusters suggests that the makeup of the α-defensin gene repertoires between primates is quite different, as their genes have undergone dramatic birth-and-death evolution. Analysis of the encoded peptides of the α-defensin genes indicates that despite the overall high level of sequence divergence, certain amino acid residues or motifs are conserved within and between the three phylogenetic classes. The evolution of α-defensins in primates, therefore, appears to be governed by two opposing evolutionary forces. One force stabilizes specific amino acid residues and motifs to preserve the functional and structural integrity of the molecules and the other diversifies the sequences generating molecules with a wide range of activities against a large number of pathogens.

PubMed Disclaimer

Figures

F<sc>IG</sc>. 1.
FIG. 1.
Phylogenetic tree condensed at the 50% bootstrap value level for α-defensin genes of five primate species. The phylogenetic trees are calculated by the (a) NJ and (b) MP methods, respectively. The pseudogenes are shown by “/” symbol. In both trees, a mouse α-defensin sequence is used as an outgroup .
F<sc>IG</sc>. 2.
FIG. 2.
Multiple sequence alignment of the functional α-defensin amino acid sequences. The conserved Cys residues are highlighted in gray and the amino acid residues or motifs that distinguish the three phylogenetic classes (classes I, II, and III) are marked with boxes. The probable consensus sequences (shown below the boxes) are the most commonly used amino acid residues (≥50%) or motifs in each α-defensin class. If only one specific residue appeared due to a substitution of the consensus residue at a particular position, that residue is shown in parentheses after the consensus sequence. If multiple residues are found in a particular position, an “X” has been used, either within parentheses after the consensus sequence or without parentheses (where no consensus found), which represents any amino acid. The potential positively selected sites are indicated by asterisks below the alignment. These sites are detected by both M2 and M8 models (see text for description). * and ** indicate significance at 95% and 99% levels, respectively.
F<sc>IG</sc>. 3.
FIG. 3.
Primate α-defensins fold similarly but have different composition of charged and surface amino acids. The theoretical 3D models for the marmoset proteins were constructed using as templates the experimentally resolved structures of human α-defensins, which are shown on the left panels for comparison. For convenience, the cartoon representations of the molecules are also shown inside the semitransparent surfaces. Three sets of amino acids are shown with different colors (blue, positive; red, negative; yellow, aromatic). The Protein Data Bank code of the templates used are 1ZMP for class I, 1ZMQ for class II, 2PM4 for class III (HNP1), and 1ZMM for class III (HNP4 ).
F<sc>IG</sc>. 4.
FIG. 4.
A representative example of flanking repetitive elements that were used to determine the orthologous relationships between α-defensin genes. Ten flanking repetitive elements from the 5′ and 3′ ends of Hsa1, Ptr1, Ppy1, and Mmu1 genes are shown. The α-defensin gene is shown as circles and the repetitive elements as rods. Rods above and below the lines indicate that the repetitive elements are located on different strands. The lines connecting the rods show orthologous and paralogous relationships of repetitive elements. The figure is not drawn in scale.
F<sc>IG</sc>. 5.
FIG. 5.
Chromosomal localization of α-defensin genes and their orthologous and paralogous relationships in human (Hsa), chimpanzee (Ptr), and macaque (Mmu). The large oval and the small oval shapes represent functional genes and pseudogenes, respectively. The rectangular shapes indicate partial genes. The open, gray, and black shapes represent class I, class II, and class III genes (as defined by the phylogenetic analysis), respectively. The lines connecting the shapes show orthologous and paralogous relationships of α-defensin genes. The figure is not drawn in scale.

Similar articles

Cited by

References

    1. Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics. 2006;22:195–201. - PubMed
    1. Bennett-Lovsey RM, Herbert AD, Sternberg MJ, Kelley LA. Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre. Proteins. 2008;70:611–625. - PubMed
    1. Boniotto M, Tossi A, DelPero M, Sgubin S, Antcheva N, Santon D, Masters J, Crovella S. Evolution of the beta defensin 2 gene in primates. Genes Immun. 2003;4:251–257. - PubMed
    1. Das S. Evolutionary origin and genomic organization of micro-RNA genes in immunoglobulin lambda variable region gene family. Mol Biol Evol. 2009;26:1179–1189. - PMC - PubMed
    1. Das S, Mohamedy U, Hirano M, Nei M, Nikolaidis N. Analysis of the immunoglobulin light chain genes in zebra finch: evolutionary implications. Mol Biol Evol. 2010;27:113–120. - PMC - PubMed

Publication types

MeSH terms

Substances