Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes

Angelica Bw Boldt,Klaus Dietz,Florian Lang,Peter G Kremsner,Iara J Messias-Reason,Jürgen Fj Kun,Diogo Meyer,Bertrand Lell,Maria Luiza Petzl-Erler,Carlos G Schrago

doi:10.1186/1471-2156-11-38

Abstract

BackgroundPolymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases.ResultsIn this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results.ConclusionUsing extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.

Highlights

Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein
To uncover the selective role diseases could have exerted on the MBL2 polymorphism, we evaluated the MBL2 promoter and exon 1 region from 856 chromosomes of Gabonese adults and children [2], as well as from 470 chromosomes belonging to individuals of European descent, and compared it with previously published data
The *1D1-h haplotype, which we found with 3% frequency in this population, was found by others with comparable frequencies (1.6 - 4.2%) in the Mbuti Pygmy, Nigerian Yoruba and Somali populations [19]. *1J1-h was found with 1.6% and 0.8% frequencies in Tanzanian Chagga and in the Somali groups, respectively. *2A1-h and *3A1-h are intermediate between P and Q containing haplotypes and most probably reminiscent of the ancient original MBL2 haplotype [2]

Summary

Introduction

Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. MBL (mannose-binding lectin) is an important component of innate immunity and a central recognition molecule of the lectin pathway of complement, which probably represents the most ancient pathway of complement activation [1]. It binds to an array of carbohydrates such as D-mannose and N-acetyl-D-glucosamine on the surface of pathogens and directly opsonizes the microorganism for phagocytosis or activates the complement system via interaction with MBL-associated serine proteases (MASP-1, -2, -3 and Map). The MBL2 genetic polymorphism is responsible for the very common and widespread variation of circulating levels of MBL oligomers and of functional activity of the protein in the human species.

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