Genetic ecological monitoring in human populations: Heterozygosity, mtDNA haplotype variation, and genetic load

Aim. In connection with the success of modern medicine, the pressure of natural selection in various civilized human populations is weakening, which leads to the accumulation of a genetic load. The purpose of this work was to trace the change in the intensity of natural selection among population of the Kirovograd region in two successive generations. Methods. The collection of material was carried out in 2020 and 2021. Anonymous questionnaires were conducted and medical histories of women of post-reproductive age of the Kirovograd region were studied. The first generation included 40 women born in 1937–1959; the second generation consists of 273 women born in 1960–1981. Results. The total selection index was 0.27 in the first generation, and 0.37 in the second generation. The percentage of women who have not had pregnancies increased from the first generation to the second from 2.5 to 3.7, respectively. Conclusions. The index of total selection in the Kirovograd region population for one generation increased by almost one and a half times (from 0.27 to 0.37), as well as the index of differential fertility (from 0.25 to 0.35). Keywords: reproductive characteristics, Kirovograd population, Crow's index, selection, generations.

Download Full-text

Genome Reduction in Tetraploid Potato Reveals Genetic Load, Haplotype Variation, and Loci Associated With Agronomic Traits

Frontiers in Plant Science ◽

10.3389/fpls.2018.00944 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 9

Author(s):

Norma C. Manrique-Carpintero ◽

Joseph J. Coombs ◽

Gina M. Pham ◽

F. Parker E. Laimbeer ◽

Guilherme T. Braz ◽

...

Keyword(s):

Agronomic Traits ◽

Genetic Load ◽

Genome Reduction ◽

Tetraploid Potato ◽

Haplotype Variation

Download Full-text

Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans

10.1101/227660 ◽

2017 ◽

Author(s):

Matthias Steinrücken ◽

Jeffrey P. Spence ◽

John A. Kamm ◽

Emilia Wieczorek ◽

Yun S. Song

Keyword(s):

Genetic Material ◽

Genetic Load ◽

Modern Human ◽

Human Populations ◽

Effective Population ◽

Weak Selection ◽

Modern Humans ◽

High Coverage ◽

Model Based ◽

And Migration

AbstractGenetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair- and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method called diCal-admix and apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.

Download Full-text

The periodical cicada four-year acceleration hypothesis revisited and the polyphyletic nature of Brood V, including an updated crowd-source enhanced map (Hemiptera: Cicadidae: Magicicada)

PeerJ ◽

10.7717/peerj.5282 ◽

2018 ◽

Vol 6 ◽

pp. e5282 ◽

Cited By ~ 2

Author(s):

John R. Cooley ◽

Nidia Arguedas ◽

Elias Bonaros ◽

Gerry Bunker ◽

Stephen M. Chiswell ◽

...

Keyword(s):

Life Cycle ◽

The United States ◽

Life Cycles ◽

Biogeographic Patterns ◽

Haplotype Variation ◽

Periodical Cicadas ◽

Different Origins ◽

Different Parts ◽

Periodical Cicada ◽

Mtdna Haplotype

The periodical cicadas of North America (Magicicada spp.) are well-known for their long life cycles of 13 and 17 years and their mass synchronized emergences. Although periodical cicada life cycles are relatively strict, the biogeographic patterns of periodical cicada broods, or year-classes, indicate that they must undergo some degree of life cycle switching. We present a new map of periodical cicada Brood V, which emerged in 2016, and demonstrate that it consists of at least four distinct parts that span an area in the United States stretching from Ohio to Long Island. We discuss mtDNA haplotype variation in this brood in relation to other periodical cicada broods, noting that different parts of this brood appear to have different origins. We use this information to refine a hypothesis for the formation of periodical cicada broods by 1- and 4-year life cycle jumps.

Download Full-text

“Genetic Load”: How the Architects of the Modern Synthesis Became Trapped in a Scientific Ideology

Transversal International Journal for the Historiography of Science ◽

10.24117/2526-2270.2018.i4.11 ◽

2018 ◽

pp. 118

Author(s):

Alexandra Soulier

Keyword(s):

Theoretical Basis ◽

Policy Making ◽

Natural Populations ◽

Genetic Load ◽

Social Progress ◽

Human Populations ◽

Complex Phenomenon ◽

Science And Policy ◽

Theodosius Dobzhansky ◽

Combined Actions

The term “genetic load” first emerged in a paper written in 1950 by the geneticist H. Muller. It is a mathematical model based on biological, social, political and ethical arguments describing the dramatic accumulation of disadvantageous mutations in human populations that will occur in modern societies if eugenic measures are not taken. The model describes how the combined actions of medical and social progress will supposedly impede natural selection and make genes of inferior quality likely to spread across populations – a process which in fine loads their progress. Genetic load is based on optimal fitness and emerges from a “typological view” of evolution. This model of evolution had previously, however, been invalidated by Robert Wright and Theodosius Dobzhansky who, as early as 1946, showed that polymorphism was the rule in natural populations. The blooming and persistence of the concept of genetic load, after its theoretical basis had already expired, are a historical puzzle. This persistence reveals the intricacy of science and policy-making in eugenic matters. The Canguilhemian concept of ‘scientific ideology’ (1988) is used along with the concept of ‘immutable mobile’ (Latour 1986) and compared with the concept of ‘co-production’ (Jasanoff 1998), to provide complementary perspectives on this complex phenomenon.

Download Full-text

Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies

Genetics ◽

10.1093/genetics/156.3.1259 ◽

2000 ◽

Vol 156 (3) ◽

pp. 1259-1275 ◽

Cited By ~ 1

Author(s):

Alan R Templeton ◽

Kenneth M Weiss ◽

Deborah A Nickerson ◽

Eric Boerwinkle ◽

Charles F Sing

Keyword(s):

Lipoprotein Lipase ◽

Association Studies ◽

Haplotype Diversity ◽

Human Populations ◽

Nucleotide Polymorphisms ◽

Lipase Gene ◽

Multiple Events ◽

General Utility ◽

Haplotype Variation ◽

Recurrent Mutations

Abstract Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3′ region should have general utility in most human populations, but the 5′ SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region.

Download Full-text

When is selection effective?

10.1101/010934 ◽

2014 ◽

Cited By ~ 5

Author(s):

Simon Gravel

Keyword(s):

Genetic Load ◽

Human Populations ◽

Deleterious Alleles ◽

Genome Wide ◽

Biological Insight ◽

Specific Allele ◽

Mutational Damage ◽

Modelling Assumptions ◽

Random Fluctuations ◽

Quantitative Explanation

AbstractDeleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In that sense, selection is more ‘effective’ in larger populations. Recent studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate. This article first seeks to clarify some terms of the debate by identifying differences in definitions and assumptions used in recent studies. We argue that variants of Morton, Crow and Muller’s ‘total mutational damage’ provide the soundest and most practical basis for such comparisons. Using simulations, analytical calculations, and 1000 Genomes data, we provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. We show that recent demography has likely modulated the effect of selection, and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary datasets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modelling assumptions, and is unlikely to provide much biological insight about human populations.

Download Full-text

Sex-specific effects of mitochondrial haplotype on metabolic rate in Drosophila melanogaster support predictions of the Mother's Curse hypothesis

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0178 ◽

2019 ◽

Vol 375 (1790) ◽

pp. 20190178 ◽

Cited By ~ 7

Author(s):

Venkatesh Nagarajan-Radha ◽

Ian Aitkenhead ◽

David J. Clancy ◽

Steven L. Chown ◽

Damian K. Dowling

Keyword(s):

Drosophila Melanogaster ◽

Life History ◽

Metabolic Rate ◽

Genetic Load ◽

Adult Life ◽

Mitochondrial Haplotype ◽

Sexual Antagonism ◽

Mtdna Mutations ◽

Mtdna Haplotypes ◽

Mtdna Haplotype

Evolutionary theory proposes that maternal inheritance of mitochondria will facilitate the accumulation of mitochondrial DNA (mtDNA) mutations that are harmful to males but benign or beneficial to females. Furthermore, mtDNA haplotypes sampled from across a given species distribution are expected to differ in the number and identity of these ‘male-harming’ mutations they accumulate. Consequently, it is predicted that the genetic variation which delineates distinct mtDNA haplotypes of a given species should confer larger phenotypic effects on males than females (reflecting mtDNA mutations that are male-harming, but female-benign), or sexually antagonistic effects (reflecting mutations that are male-harming, but female-benefitting). These predictions have received support from recent work examining mitochondrial haplotypic effects on adult life-history traits in Drosophila melanogaster . Here, we explore whether similar signatures of male-bias or sexual antagonism extend to a key physiological trait—metabolic rate. We measured the effects of mitochondrial haplotypes on the amount of carbon dioxide produced by individual flies, controlling for mass and activity, across 13 strains of D. melanogaster that differed only in their mtDNA haplotype. The effects of mtDNA haplotype on metabolic rate were larger in males than females. Furthermore, we observed a negative intersexual correlation across the haplotypes for metabolic rate. Finally, we uncovered a male-specific negative correlation, across haplotypes, between metabolic rate and longevity. These results are consistent with the hypothesis that maternal mitochondrial inheritance has led to the accumulation of a sex-specific genetic load within the mitochondrial genome, which affects metabolic rate and that may have consequences for the evolution of sex differences in life history. This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.

Download Full-text

Prediction of mitochondrial genome-wide variation through sequencing of mitochondrion-enriched extracts

Scientific Reports ◽

10.1038/s41598-020-76088-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kelsey E. Fisher ◽

Steven P. Bradbury ◽

Brad S. Coates

Keyword(s):

Mitochondrial Genome ◽

Nadh Dehydrogenase ◽

High Throughput Sequencing ◽

De Novo ◽

Short Read ◽

Deletion Mutations ◽

Haplotype Variation ◽

Cell Extracts ◽

Genome Wide ◽

Mtdna Haplotype

Abstract Although mitochondrial DNA (mtDNA) haplotype variation is often applied for estimating population dynamics and phylogenetic relationships, economical and generalized methods for entire mtDNA genome enrichment prior to high-throughput sequencing are not readily available. This study demonstrates the utility of differential centrifugation to enrich for mitochondrion within cell extracts prior to DNA extraction, short-read sequencing, and assembly using exemplars from eight maternal lineages of the insect species, Ostrinia nubilalis. Compared to controls, enriched extracts showed a significant mean increase of 48.2- and 86.1-fold in mtDNA based on quantitative PCR, and proportion of subsequent short sequence reads that aligned to the O. nubilalis reference mitochondrial genome, respectively. Compared to the reference genome, our de novo assembled O. nubilalis mitochondrial genomes contained 82 intraspecific substitution and insertion/deletion mutations, and provided evidence for correction of mis-annotated 28 C-terminal residues within the NADH dehydrogenase subunit 4. Comparison to a more recent O. nubilalis mtDNA assembly from unenriched short-read data analogously showed 77 variant sites. Twenty-eight variant positions, and a triplet ATT codon (Ile) insertion within ATP synthase subunit 8, were unique within our assemblies. This study provides a generalizable pipeline for whole mitochondrial genome sequence acquisition adaptable to applications across a range of taxa.

Download Full-text

Сytogenetic techniques in current biomedical research. part i: history and theoretical basis of human cytogenetics

Fundamental and Clinical Medicine ◽

10.23946/2500-0764-2021-6-4-142-150 ◽

2021 ◽

Vol 6 (4) ◽

pp. 142-150

Author(s):

A. N. Volkov ◽

L. V. Nacheva

Keyword(s):

Molecular Basis ◽

Human Genetics ◽

Chromosomal Abnormalities ◽

Unmet Need ◽

Genetic Load ◽

Reproductive Function ◽

Human Populations ◽

Chromosomal Structure ◽

Social Burden ◽

Human Cytogenetics

Cytogenetics is an essential part of human genetics which studies the structure of chromosomes and their collection which is called karyotype. Cytogenetic techniques are employed while interrogating DNA organisation and compaction. Analysis of the chromosomal structure contributes to uncovering the molecular basis of various cellular processes in normal and pathological conditions. Furthermore, spectrum and frequency of chromosome abnormalities serves as an indicator of mutagenic effects. Cytogenetic techniques became indispensable for discovering the genetic causes of human diseases at different stages of ontogenesis. Genetic abnormalities are a common cause of impaired reproductive function, abnormal pregnancy, and neonatal malformations. Genetic screening for chromosomal abnormalities and congenital anomalies is a powerful tool for reducing the genetic load in human populations as well as disease, psychological and social burden on families and societies. This paper begins the cycle of lectures on molecular basis of human cytogenetics, cytogenetic techniques, and the corresponding research and clinical applications. The lecture is primarily aimed at biomedical students and physicians who often have an unmet need to analyse and interpret the results of cytogenetic analyses.

Download Full-text