Searching for signals of recent natural selection in genes of the innate immune response - ancient DNA study

Lewandowska, Magda; Jędrychowska-Dańska, Krystyna; Płoszaj, Tomasz; Witas, Piotr; Zamerska, Alicja; Mańkowska-Pliszka, Hanna; Witas, Henryk W.

doi:10.1016/j.meegid.2018.05.008

Cited by 6 publications

(3 citation statements)

References 82 publications

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“…Although studies on the evolution of cytokines and their receptors suggest that IL10 and IL10RA may be subject to natural selection in response to pathogens, especially parasites [59][60][61], balancing selection of pathogenic genetic variants has not specifically been demonstrated. Our data suggest that accumulation of pathogenic IL10RA variants is not due to a limited "founder effect" and geographical isolation.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Interleukin-10 Receptor Alpha Variants in Humans — Balancing Natural Selection and Clinical Implications

Aschenbrenner

Zhou

et al. 2022

J Clin Immunol

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Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We identify 36 non-synonymous and non-sense variants in the IL10RA gene. Since the majority of these IL10RA variants have not been functionally characterized, we performed a systematic screening of their impact on STAT3 phosphorylation upon IL-10 stimulation. Based on the geographic accumulation of confirmed pathogenic IL10RA variants in East Asia and in Northeast China, the distribution of infectious disorders worldwide, and the functional evidence of IL-10 signaling in the pathogenesis, we identify Schistosoma japonicum infection as plausible selection pressure driving variation in IL10RA. Consistent with this is a partially augmented IL-10 response in peripheral blood mononuclear cells from heterozygous variant carriers. A parasite-driven heterozygote advantage through reduced IL-10 signaling has implications for health care utilization in regions with high allele frequencies and potentially indicates pathogen eradication strategies that target IL-10 signaling. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Pathogenic Interleukin-10 Receptor Alpha Variants in Humans — Balancing Natural Selection and Clinical Implications

Aschenbrenner

Zhou

et al. 2022

J Clin Immunol

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“…Polymorphic sites in innateimmunity genes associated with predisposition to mycobacterial infections (SLC11A1, MBL2, TLR2, P2RX7, IL10, and TNFA) have been studied in remains of 151 people in time series data (1st-18th centuries AD) from Northern and Eastern Poland (Lewandowska et al, 2018). This DNA analysis indicated that genetic drift has played the main role in the evolution of people in this region; however, two SNVs (rs17235409 of the divalent cation transporter SLC11A1 gene and rs1800896 of interleukin IL10 gene) manifested signs of nonrandom evolution.…”

Section: Comparison Of Genomes Of Ancient and Modern Humansmentioning

confidence: 99%

Problems with studying directional natural selection in humans

Mikhailova

2023

Vestn. VOGiS

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The review describes the main methods for assessing directional selection in human populations. These include bioinformatic analysis of DNA sequences via detection of linkage disequilibrium and of deviations from the random distribution of frequencies of genetic variants, demographic and anthropometric studies based on a search for a correlation between fertility and phenotypic traits, genome-wide association studies on fertility along with genetic loci and polygenic risk scores, and a comparison of allele frequencies between generations (in modern samples and in those obtained from burials). Each approach has its limitations and is applicable to different periods in the evolution of Homo sapiens. The main source of error in such studies is thought to be sample stratification, the small number of studies on nonwhite populations, the impossibility of a complete comparison of the associations found and functionally significant causative variants, and the difficulty with taking into account all nongenetic determinants of fertility in contemporary populations. The results obtained by various methods indicate that the direction of human adaptation to new food products has not changed during evolution since the Neolithic; many variants of immunity genes associated with inflammatory and autoimmune diseases in modern populations have undergone positive selection over the past 2–3 thousand years owing to the spread of bacterial and viral infections. For some genetic variants and polygenic traits, an alteration of the direction of natural selection in Europe has been documented, e. g., for those associated with an immune response and cognitive abilities. Examination of the correlation between fertility and educational attainment yields conflicting results. In modern populations, to a greater extent than previously, there is selection for variants of genes responsible for social adaptation and behavioral phenotypes. In particular, several articles have shown a positive correlation of fertility with polygenic risk scores of attention deficit/hyperactivity disorder.

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“…Comparing allele frequencies between burials of different ages and modern populations makes it possible to identify genes that have been under selection pressure in the past. In time series data from Poland (1st-18th centuries AD), polymorphic sites in the six innate-immunity genes that are associated with predisposition to mycobacterial infections have been analyzed [7]. Signs of selection were found there for rs17235409 of the SLC11A1 gene and for rs1800896 of the IL10 gene; this phenomenon may be due to the spread of tuberculosis in Europe.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

Mikhailova,

Ivanoshchuk,

Orlov

et al. 2023

Genes

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Background: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress. Methods: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations. Results: In the “crisis” group, a statistically significant difference from the other two groups was found in rs6557168 frequency (p = 0.001); rs4522666 was not in the Hardy–Weinberg equilibrium in this group, although its frequency did not show a significant difference from the other groups (p = 0.118). Frequencies of VNTRs in SLC6A3 and MAOA as well as common variants rs17689918 in CRHR1, rs1360780 in FKBP5, rs53576 in OXTR, rs12720071 and rs806377 in CNR1, rs4311 in ACE, rs1800497 in ANKK1, and rs7412 and rs429358 in APOE did not differ among the groups. Conclusions: a generation born during a period of prolonged destructive events may differ from the rest of the gene pool of the population in some variants associated with personality traits or stress-related disorders.

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Searching for signals of recent natural selection in genes of the innate immune response - ancient DNA study

Cited by 6 publications

References 82 publications

Pathogenic Interleukin-10 Receptor Alpha Variants in Humans — Balancing Natural Selection and Clinical Implications

Pathogenic Interleukin-10 Receptor Alpha Variants in Humans — Balancing Natural Selection and Clinical Implications

Problems with studying directional natural selection in humans

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

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