The 5q31 Region in Two African Populations as a Facet of Natural Selection by Infectious Diseases

The immune system's function is to protect against microorganisms, but infection is nonetheless the most frequent cause of death in human history. Until the last century, life expectancy was only ∼25 years. Recent increases in human life span primarily reflect the development of hygiene, vaccines, and anti-infectious drugs, rather than the adjustment of our immune system to coevolving microbes by natural selection. We argue here that most individuals retain a natural vulnerability to infectious diseases, reflecting a great diversity of inborn errors of immunity.

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Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2011.0299 ◽

2012 ◽

Vol 367 (1590) ◽

pp. 868-877 ◽

Cited By ~ 74

Author(s):

Kristian G. Andersen ◽

Ilya Shylakhter ◽

Shervin Tabrizi ◽

Sharon R. Grossman ◽

Christian T. Happi ◽

...

Keyword(s):

Natural Selection ◽

Positive Selection ◽

Lassa Fever ◽

West African ◽

Lassa Virus ◽

Genome Wide ◽

African Populations ◽

Genome Wide Data ◽

Differential Gene ◽

Selection Of

Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 ( IL21 ), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21 . Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit.

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Evidence for Natural Selection and Ethnic Diversity at the Adenylate cyclase 3 Gene Associated with Obesity and Type 2 Diabetes

10.21203/rs.3.rs-18469/v1 ◽

2020 ◽

Author(s):

ISSEI YOSHIUCHI

Keyword(s):

Type 2 Diabetes ◽

Natural Selection ◽

Adenylate Cyclase ◽

Ethnic Diversity ◽

European Ancestry ◽

Loss Of Function ◽

Obesity And Diabetes ◽

African Populations ◽

Diabetes And Obesity

Abstract Background: Diabetes and obesity cause serious complications worldwide, including stroke and cardiovascular disease, and are a global health burden. Diabetes is strongly related with obesity and both are significantly heritable. The prevalence of diabetes and obesity are higher in African populations than in European and Asian populations. In human evolution, natural selection is a key process of genetic survival over generations. Thus, the selection for diabetes- and obesity-related genes is a key mechanism for survival during times of feast and famine. Loss-of-function variations in the adenylate cyclase 3 ( ADCY3 ) gene are associated with obesity and diabetes, while mutations in ADCY3 are also associated with childhood obesity. ADCY3 -deficient mice showed severe obesity, impaired insulin sensitivity, and reduced physical activity. Here, we researched evidence for natural selection at ADCY3 . Methods: We used a three-step genetic method to identify natural selection at ADCY3 using data on four populations from the 1000 Genomes Project and HapMap: Utah residents with Northern and Western European ancestry (CEU), the Yoruba in Ibadan, Nigeria (YRI), Han Chinese in Beijing (CHB) and Japanese in Tokyo (JPT). First we used Wright’s F-statistics (Fst) as a measure of population differentiation to find ethnic diversity at ADCY3 . We then used a long-range haplotype (LRH) test to find significant long haplotypes, and then the integrated haplotype score (iHS) to find natural selection at ADCY3 . Results: We observed high Fst values and significant ethnic diversity at four ADCY3 body mass index (BMI)-associated variations (rs7586879, rs6545814, rs11676272 and rs10182181) between the non-African and African populations. Both LRH and iHS also provided evidence for natural selection at ADCY3 . Conclusions: These observations show evidence for natural selection and ethnic diversity at ADCY3 . Further exploration into the evolution of obesity- and Type 2 diabetes-associated genes is needed.

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Adaptation to infectious disease exposure in indigenous Southern African populations

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2017.0226 ◽

2017 ◽

Vol 284 (1852) ◽

pp. 20170226 ◽

Cited By ~ 10

Author(s):

Katharine A. Owers ◽

Per Sjödin ◽

Carina M. Schlebusch ◽

Pontus Skoglund ◽

Himla Soodyall ◽

...

Keyword(s):

Infectious Diseases ◽

Extreme Values ◽

Dual Approach ◽

Immune Genes ◽

Genomic Signatures ◽

African Populations ◽

Signatures Of Selection ◽

Genomic Regions ◽

Disease Exposure ◽

Two Populations

Genetic analyses can provide information about human evolutionary history that cannot always be gleaned from other sources. We evaluated evidence of selective pressure due to introduced infectious diseases in the genomes of two indigenous southern African San groups—the ‡Khomani who had abundant contact with other people migrating into the region and the more isolated Ju|’hoansi. We used a dual approach to test for increased selection on immune genes compared with the rest of the genome in these groups. First, we calculated summary values of statistics that measure genomic signatures of adaptation to contrast selection signatures in immune genes and all genes. Second, we located regions of the genome with extreme values of three selection statistics and examined these regions for enrichment of immune genes. We found stronger and more abundant signals of selection in immune genes in the ‡Khomani than in the Ju|’hoansi. We confirm this finding within each population to avoid effects of different demographic histories of the two populations. We identified eight immune genes that have potentially been targets of strong selection in the ‡Khomani, whereas in the Ju|’hoansi, no immune genes were found in the genomic regions with the strongest signals of selection. We suggest that the more abundant signatures of selection at immune genes in the ‡Khomani could be explained by their more frequent contact with immigrant groups, which likely led to increased exposure and adaptation to introduced infectious diseases.

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The ancient battle for iron: Our struggle with pathogens

The Biochemist ◽

10.1042/bio02506015 ◽

2003 ◽

Vol 25 (6) ◽

pp. 15-18 ◽

Cited By ~ 1

Author(s):

Andrew Prentice ◽

Conor Doherty ◽

Joann McDermid ◽

Sarah Atkinson ◽

Sharon Cox

Keyword(s):

Plasmodium Falciparum ◽

Natural Selection ◽

Young Children ◽

Infectious Diseases ◽

Medical Care ◽

Falciparum Malaria ◽

Rainy Season ◽

Respiratory Infections ◽

Plasmodium Falciparum Malaria ◽

The Impact

Young children in rural Gambia face constant exposure to gastrointestinal and respiratory infections and, during the rainy season (July–November), suffer recurrent bouts of Plasmodium falciparum malaria. Within living memory, these conditions led to more than half of the children dying before their fifth birthday, providing a graphic demonstration of the impact that infectious diseases have had on our natural selection. Fortunately, these horrific statistics have been decreased greatly by improved medical care, especially through vaccination and anti-malarial therapies, but conditions such as these have inevitably left a powerful imprint on man's genetic make-up.

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Epigenetic inheritance and the evolution of infectious diseases

10.1101/2020.08.29.273326 ◽

2020 ◽

Author(s):

David V. McLeod ◽

Geoff Wild ◽

Francisco Úbeda

Keyword(s):

Natural Selection ◽

Infectious Diseases ◽

Dna Sequences ◽

Personalised Medicine ◽

Epigenetic Inheritance ◽

Social Differences ◽

Epigenetic Marks ◽

Evolution Of Virulence ◽

The Impact ◽

Past Conditions

AbstractGenes with identical DNA sequences may show differential expression because of epigenetic marks. These marks in pathogens are key to their virulence and are being evaluated as targets for medical treatment. Where epigenetic marks were created in response to past conditions (epigenetically inherited), they represent a form of memory, the impact of which has not been considered in the evolution of infectious diseases. We fill this gap by exploring the evolution of virulence in pathogens that inherit epigenetic information on the sex of their previous host. We show that memories of past hosts can also provide clues about the sex of present and future hosts when women and men differ in their immunity to infection and/or their interactions with the sexes. These biological and social differences between the sexes are pervasive in humans. We show that natural selection can favour the evolution of greater virulence in infections originating from one sex. Furthermore, natural selection can favour the evolution of greater virulence in infections across sexes (or within sexes). Our results explain certain patterns of virulence in diseases like measles, chickenpox and polio that have puzzled medical researchers for decades. In particular, they address why girls infected by boys (or boys infected by girls) are more likely to die from the infection than girls infected by girls (or boys infected by boys). We propose epigenetic therapies to treat infections by tampering with the memories of infecting pathogens. Counterintuitively, we predict that successful therapies should target pathogen’s genes that inhibit virulence, rather than those enhancing virulence. Our findings imply that pathogens can carry memories of past environments other than sex (e.g. those related to socioeconomic status) that may condition their virulence and could signify an important new direction in personalised medicine.

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No evidence that natural selection has been less effective at removing deleterious mutations in Europeans than in West Africans

10.1101/002865 ◽

2014 ◽

Cited By ~ 5

Author(s):

Ron Do ◽

Daniel Balick ◽

Heng Li ◽

Ivan Adzhubei ◽

Shamil Sunyaev ◽

...

Keyword(s):

Natural Selection ◽

Neutral Evolution ◽

Deleterious Mutations ◽

Modern Humans ◽

Synonymous Mutations ◽

Separation Time ◽

Effective Removal ◽

African Populations ◽

West Africans

AbstractNon-African populations have experienced major bottlenecks in the time since their split from West Africans, which has led to the hypothesis that natural selection to remove weakly deleterious mutations may have been less effective in non-Africans. To directly test this hypothesis, we measure the per-genome accumulation of deleterious mutations across diverse humans. We fail to detect any significant differences, but find that archaic Denisovans accumulated non-synonymous mutations at a higher rate than modern humans, consistent with the longer separation time of modern and archaic humans. We also revisit the empirical patterns that have been interpreted as evidence for less effective removal of deleterious mutations in non-Africans than in West Africans, and show they are not driven by differences in selection after population separation, but by neutral evolution.

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Evolutionary advantages of turning points in human cooperative behaviour

PLoS ONE ◽

10.1371/journal.pone.0246278 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246278

Author(s):

Daniele Vilone ◽

John Realpe-Gómez ◽

Giulia Andrighetto

Keyword(s):

Natural Selection ◽

Infectious Diseases ◽

Turning Point ◽

Environmental Conservation ◽

Cooperative Groups ◽

Cooperative Behaviour ◽

Social Scientists ◽

Social Challenges ◽

Free Riders ◽

Theoretical Evidence

Cooperation is crucial to overcome some of the most pressing social challenges of our times, such as the spreading of infectious diseases, corruption and environmental conservation. Yet, how cooperation emerges and persists is still a puzzle for social scientists. Since human cooperation is individually costly, cooperative attitudes should have been eliminated by natural selection in favour of selfishness. Yet, cooperation is common in human societies, so there must be some features which make it evolutionarily advantageous. Using a cognitive inspired model of human cooperation, recent work Realpe-Gómez (2018) has reported signatures of criticality in human cooperative groups. Theoretical evidence suggests that being poised at a critical point provides evolutionary advantages to groups by enhancing responsiveness of these systems to external attacks. After showing that signatures of criticality can be detected in human cooperative groups composed by Moody Conditional Cooperators, in this work we show that being poised close to a turning point enhances the fitness and make individuals more resistant to invasions by free riders.

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