The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease
JF Brinkworth, LB Barreiro - Current opinion in immunology, 2014 - Elsevier
Current opinion in immunology, 2014•Elsevier
Highlights•GWAS suggest pathological inflammation is controlled by a small network of
genes.•Many chronic inflammatory/autoimmune risk alleles occur in regions of positive
selection.•Chronic inflammatory/autoimmune risk alleles may be the outcome of an
evolutionary trade off.•Pathogen-mediated selection might have driven the increase in
frequency of inflammatory/autoimmune risk alleles.•Major cultural changes such as the
advent of agriculture likely affected diversification of human immunity.Chronic inflammatory …
genes.•Many chronic inflammatory/autoimmune risk alleles occur in regions of positive
selection.•Chronic inflammatory/autoimmune risk alleles may be the outcome of an
evolutionary trade off.•Pathogen-mediated selection might have driven the increase in
frequency of inflammatory/autoimmune risk alleles.•Major cultural changes such as the
advent of agriculture likely affected diversification of human immunity.Chronic inflammatory …
Highlights
- GWAS suggest pathological inflammation is controlled by a small network of genes.
- Many chronic inflammatory/autoimmune risk alleles occur in regions of positive selection.
- Chronic inflammatory/autoimmune risk alleles may be the outcome of an evolutionary trade off.
- Pathogen-mediated selection might have driven the increase in frequency of inflammatory/autoimmune risk alleles.
- Major cultural changes such as the advent of agriculture likely affected diversification of human immunity.
Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the important roles the implicated immune genes play in pathogen defense and other functions thought to be under strong natural selection in humans. The evolutionary reasons for chronic inflammatory and autoimmune disease persistence and uneven distribution across populations are the focus of this review.
Elsevier