Limits...
Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates.

Clough D, Kappeler PM, Walter L - Front. Zool. (2011)

Bottom Line: The evolutionary and functional significance of single nucleotide polymorphisms (SNPs) in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking.Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area.Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected.

View Article: PubMed Central - HTML - PubMed

Affiliation: Behavioral Ecology and Sociobiology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany. dclough@gwdg.de.

ABSTRACT

Background: Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4) plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs) in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae), from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success.

Results: Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected.

Conclusions: Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better understanding of the actual components of the immune response that mediate protection against gastro-intestinal parasites.

No MeSH data available.


Related in: MedlinePlus

Eulemur fulvus rufus IL4 promoter sequence. Alignment of Eulemur fulvus rufus IL4 promoter sequence (GenBank accession GQ221019) with published sequences of human [Hs, 70], Macaca mulatta [Mm, 71] and Cercocebus atys [Ca, 71]. Highlighted are the lemur -485C/T SNP, the human -589C/T SNP, and the TATA box. Gaps introduced to maximise similarity are marked by "+". Nucleotides identical to the lemur sequence (Efr_1_CC) are shown by dashes. Nucleotide numbering is based on the human sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3104205&req=5

Figure 1: Eulemur fulvus rufus IL4 promoter sequence. Alignment of Eulemur fulvus rufus IL4 promoter sequence (GenBank accession GQ221019) with published sequences of human [Hs, 70], Macaca mulatta [Mm, 71] and Cercocebus atys [Ca, 71]. Highlighted are the lemur -485C/T SNP, the human -589C/T SNP, and the TATA box. Gaps introduced to maximise similarity are marked by "+". Nucleotides identical to the lemur sequence (Efr_1_CC) are shown by dashes. Nucleotide numbering is based on the human sequence.

Mentions: After sequencing a 528 bp fragment of the IL4 promoter region of the red-fronted lemur, we identified a C/T polymorphism at position -485 bp upstream of the transcription start site (Figure 1). The -485 C/T was the only SNP found within this part of the promoter sequence. All possible genotypes (C/C, C/T, T/T) were present in the total lemur population studied between 1996 and 2007 (N = 64 individuals) with the following frequencies: C/C: 51.6% (n = 33 individuals), C/T: 37.5% (n = 24), T/T: 10.9% (n = 7). In a subset of this dataset, which was used for combined parasitological and genetic analyses (see below; yr 2007, n = 24 individuals) frequency distribution was C/C: 50.0% (n = 12 individuals), C/T: 37.5% (n = 9), T/T: 12.5% (n = 3). Frequency distribution of genotypes did not deviate from a distribution expected under Hardy-Weinberg equilibrium (Fisher's exact test, p = 0.86, df = 2).


Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates.

Clough D, Kappeler PM, Walter L - Front. Zool. (2011)

Eulemur fulvus rufus IL4 promoter sequence. Alignment of Eulemur fulvus rufus IL4 promoter sequence (GenBank accession GQ221019) with published sequences of human [Hs, 70], Macaca mulatta [Mm, 71] and Cercocebus atys [Ca, 71]. Highlighted are the lemur -485C/T SNP, the human -589C/T SNP, and the TATA box. Gaps introduced to maximise similarity are marked by "+". Nucleotides identical to the lemur sequence (Efr_1_CC) are shown by dashes. Nucleotide numbering is based on the human sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104205&req=5

Figure 1: Eulemur fulvus rufus IL4 promoter sequence. Alignment of Eulemur fulvus rufus IL4 promoter sequence (GenBank accession GQ221019) with published sequences of human [Hs, 70], Macaca mulatta [Mm, 71] and Cercocebus atys [Ca, 71]. Highlighted are the lemur -485C/T SNP, the human -589C/T SNP, and the TATA box. Gaps introduced to maximise similarity are marked by "+". Nucleotides identical to the lemur sequence (Efr_1_CC) are shown by dashes. Nucleotide numbering is based on the human sequence.
Mentions: After sequencing a 528 bp fragment of the IL4 promoter region of the red-fronted lemur, we identified a C/T polymorphism at position -485 bp upstream of the transcription start site (Figure 1). The -485 C/T was the only SNP found within this part of the promoter sequence. All possible genotypes (C/C, C/T, T/T) were present in the total lemur population studied between 1996 and 2007 (N = 64 individuals) with the following frequencies: C/C: 51.6% (n = 33 individuals), C/T: 37.5% (n = 24), T/T: 10.9% (n = 7). In a subset of this dataset, which was used for combined parasitological and genetic analyses (see below; yr 2007, n = 24 individuals) frequency distribution was C/C: 50.0% (n = 12 individuals), C/T: 37.5% (n = 9), T/T: 12.5% (n = 3). Frequency distribution of genotypes did not deviate from a distribution expected under Hardy-Weinberg equilibrium (Fisher's exact test, p = 0.86, df = 2).

Bottom Line: The evolutionary and functional significance of single nucleotide polymorphisms (SNPs) in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking.Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area.Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected.

View Article: PubMed Central - HTML - PubMed

Affiliation: Behavioral Ecology and Sociobiology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany. dclough@gwdg.de.

ABSTRACT

Background: Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4) plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs) in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae), from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success.

Results: Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected.

Conclusions: Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better understanding of the actual components of the immune response that mediate protection against gastro-intestinal parasites.

No MeSH data available.


Related in: MedlinePlus