QTL mapping and the genetic basis of adaptation: recent developments

Association mapping was used to investigate the genetic basis of variation within Brassica rapa , which is an important vegetable and oil crop. We analyzed the variation of phytate and phosphate levels in seeds and leaves and additional developmental and morphological traits in a set of diverse B. rapa accessions and tested association of these traits with AFLP markers. The analysis of population structure revealed four subgroups in the population. Trait values differed between these subgroups, thus defining associations between population structure and trait values, even for traits such as phytate and phosphate levels. Marker–trait associations were investigated both with and without taking population structure into account. One hundred and seventy markers were found to be associated with the observed traits without correction for population structure. Association analysis with correction for population structure led to the identification of 27 markers, 6 of which had known map positions; 3 of these were confirmed in additional QTL mapping studies.

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QTL Mapping of a Brazilian Bioethanol Strain Unravels the Cell Wall Protein-Encoding Gene GAS1 as a Major Contributor to Low Ph Tolerance in S. Cerevisiae

10.21203/rs.3.rs-827768/v1 ◽

2021 ◽

Author(s):

Alessandro L V Coradini ◽

Fellipe da Silveira Bezerra de Mello ◽

Monique Furlan ◽

Carla Maneira ◽

Marcello Falsarella Carazzolle ◽

...

Keyword(s):

Qtl Mapping ◽

Genetic Architecture ◽

Genetic Basis ◽

Acid Resistance ◽

Low Ph ◽

Susceptible Strain ◽

Yeast Cells ◽

Synonymous Mutation ◽

Major Contributor ◽

Ph Tolerance

Abstract BACKGROUNDSaccharomyces cerevisiae is largely applied in many biotechnological processes, from traditional food and beverage industries to modern biofuel and biochemicals factories. During the fermentation process, yeast cells are usually challenged in different harsh conditions, which often impact productivity. Regarding bioethanol production, cell exposure to acidic environments is related to productivity loss on both first and second generation ethanol. In this scenario, indigenous strains traditionally used in fermentation stand out as a source of complex genetic architecture, mainly due to their highly robust background - including low pH tolerance. RESULTSIn this work, we pioneer the use of QTL mapping to uncover the genetic basis that endow industrial strain Pedra-2 (PE-2) with outstanding acid resistance. First, we developed a fluorescence-based high-throughput approach to collect a large number of haploid cells using flow cytometry. Then, we were able to apply a bulk segregant analysis to solve the genetic basis of low pH resistance in PE-2, which uncovered a region in chromosome XIII as the major QTL associated with the evaluated phenotype. A reciprocal hemizygosity analysis revealed allele GAS1, encoding a β-1,3-glucanosyltransferase, as the major contributor to this phenotype. The GAS1 sequence alignment of 48 S. cerevisiae strains pointed out a non-synonymous mutation (T211A) prevalence in wild type isolates, which is absent in laboratory strains. We further showcase that GAS1 allele swap between PE-2 and a low pH-susceptible strain can improve cell viability on the latter of up to 12% after a sulfuric acid wash process.CONCLUSIONThis work revealed GAS1 as the major causative gene associated with low pH resistance in PE-2, harboring a non-synonymous mutation persistent in industrial strains. We also showcase how GAS1PE-2 can improve acid resistance of a susceptible strain, suggesting that these findings can be a powerful foundation for the development of more robust and acid-tolerant strains for the industrial production of economically-relevant goods. Our results collectively show the importance of tailored industrial isolated strains in the discovery of the genetic architecture of relevant traits and its implications over productivity.

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Barcoded Bulk QTL mapping reveals highly polygenic and epistatic architecture of complex traits in yeast

10.1101/2021.09.08.459513 ◽

2021 ◽

Author(s):

Alex N. Nguyen Ba ◽

Katherine R. Lawrence ◽

Artur Rego-Costa ◽

Shreyas Gopalakrishnan ◽

Daniel Temko ◽

...

Keyword(s):

Quantitative Trait Locus ◽

Qtl Mapping ◽

Quantitative Trait ◽

Complex Traits ◽

Large Scale ◽

Genetic Basis ◽

Association Studies ◽

Model Organisms ◽

Genome Wide Association Studies ◽

Trait Locus

Mapping the genetic basis of complex traits is critical to uncovering the biological mechanisms that underlie disease and other phenotypes. Genome-wide association studies (GWAS) in humans and quantitative trait locus (QTL) mapping in model organisms can now explain much of the observed heritability in many traits, allowing us to predict phenotype from genotype. However, constraints on power due to statistical confounders in large GWAS and smaller sample sizes in QTL studies still limit our ability to resolve numerous small-effect variants, map them to causal genes, identify pleiotropic effects across multiple traits, and infer non-additive interactions between loci (epistasis). Here, we introduce barcoded bulk quantitative trait locus (BB-QTL) mapping, which allows us to construct, genotype, and phenotype 100,000 offspring of a budding yeast cross, two orders of magnitude larger than the previous state of the art. We use this panel to map the genetic basis of eighteen complex traits, finding that the genetic architecture of these traits involves hundreds of small-effect loci densely spaced throughout the genome, many with widespread pleiotropic effects across multiple traits. Epistasis plays a central role, with thousands of interactions that provide insight into genetic networks. By dramatically increasing sample size, BB-QTL mapping demonstrates the potential of natural variants in high-powered QTL studies to reveal the highly polygenic, pleiotropic, and epistatic architecture of complex traits.Significance statementUnderstanding the genetic basis of important phenotypes is a central goal of genetics. However, the highly polygenic architectures of complex traits inferred by large-scale genome-wide association studies (GWAS) in humans stand in contrast to the results of quantitative trait locus (QTL) mapping studies in model organisms. Here, we use a barcoding approach to conduct QTL mapping in budding yeast at a scale two orders of magnitude larger than the previous state of the art. The resulting increase in power reveals the polygenic nature of complex traits in yeast, and offers insight into widespread patterns of pleiotropy and epistasis. Our data and analysis methods offer opportunities for future work in systems biology, and have implications for large-scale GWAS in human populations.

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Mutation in an Unannotated Protein Confers Carbapenem Resistance in Mycobacterium tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02234-16 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 9

Author(s):

Pankaj Kumar ◽

Amit Kaushik ◽

Drew T. Bell ◽

Varsha Chauhan ◽

Fangfang Xia ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Genetic Basis ◽

Carbapenem Resistance ◽

Drug Resistant ◽

Binding Affinities ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Content Type ◽

Resistant Tuberculosis ◽

Recent Developments

ABSTRACT β-Lactams are the most widely used antibacterials. Among β-lactams, carbapenems are considered the last line of defense against recalcitrant infections. As recent developments have prompted consideration of carbapenems for treatment of drug-resistant tuberculosis, it is only a matter of time before Mycobacterium tuberculosis strains resistant to these drugs will emerge. In the present study, we investigated the genetic basis that confers such resistance. To our surprise, instead of mutations in the known β-lactam targets, a single nucleotide polymorphism in the Rv2421c-Rv2422 intergenic region was common among M. tuberculosis mutants selected with meropenem or biapenem. We present data supporting the hypothesis that this locus harbors a previously unidentified gene that encodes a protein. This protein binds to β-lactams, slowly hydrolyzes the chromogenic β-lactam nitrocefin, and is inhibited by select penicillins and carbapenems and the β-lactamase inhibitor clavulanate. The mutation results in a W62R substitution that reduces the protein's nitrocefin-hydrolyzing activity and binding affinities for carbapenems.

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Dissection of the genetic basis of heterosis in an elite maize hybrid by QTL mapping in an immortalized F2 population

Theoretical and Applied Genetics ◽

10.1007/s00122-009-1213-0 ◽

2009 ◽

Vol 120 (2) ◽

pp. 333-340 ◽

Cited By ~ 82

Author(s):

Jihua Tang ◽

Jianbing Yan ◽

Xiqing Ma ◽

Wentao Teng ◽

Weiren Wu ◽

...

Keyword(s):

Qtl Mapping ◽

Genetic Basis ◽

Maize Hybrid ◽

F2 Population ◽

Immortalized F2

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Evolutionary Ethics and the Search for Predecessors: Kant, Hume, and All the Way Back to Aristotle?

Social Philosophy and Policy ◽

10.1017/s0265052500003745 ◽

1990 ◽

Vol 8 (1) ◽

pp. 59-85 ◽

Cited By ~ 11

Author(s):

Michael Ruse

Keyword(s):

Social Behavior ◽

Evolutionary Biology ◽

Genetic Basis ◽

Evolutionary Ethics ◽

Recent Developments ◽

The Creation ◽

The Way

Hopes of applying the findings and speculations of evolutionary theorizing to the problems of ethics have yielded a program with a (deservedly) bad reputation. At the level of norms – substantival ethics – it has been a platform for some of the more grotesque socio-politico-economic suggestions of our times. At the level of justification – metaethics – it has opened the way to some of the more blatant fallacies in the undergraduate textbook. Recently, however, a number of people, philosophers and biologists, have sensed that a more adequate evolutionary ethics might be possible. United in the conviction that it simply has to matter that we humans are modified monkeys rather than the creation of a Good God, in His image, on the Sixth Day, they argue that recent developments in evolutionary biology, especially those dealing with the genetic basis of social behavior (“sociobiology”), open the way to a satisfactory biological understanding of morality.

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QTL mapping of a Brazilian bioethanol strain links the cell wall protein-encoding gene GAS1 to low pH tolerance in S. cerevisiae

Biotechnology for Biofuels ◽

10.1186/s13068-021-02079-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Alessandro L. V. Coradini ◽

Fellipe da Silveira Bezerra de Mello ◽

Monique Furlan ◽

Carla Maneira ◽

Marcelo F. Carazzolle ◽

...

Keyword(s):

Qtl Mapping ◽

Genetic Architecture ◽

Genetic Basis ◽

Productivity Loss ◽

Acid Resistance ◽

Low Ph ◽

Susceptible Strain ◽

Yeast Cells ◽

Ph Tolerance ◽

Food And Beverage

Abstract Background Saccharomyces cerevisiae is largely applied in many biotechnological processes, from traditional food and beverage industries to modern biofuel and biochemicals factories. During the fermentation process, yeast cells are usually challenged in different harsh conditions, which often impact productivity. Regarding bioethanol production, cell exposure to acidic environments is related to productivity loss on both first- and second-generation ethanol. In this scenario, indigenous strains traditionally used in fermentation stand out as a source of complex genetic architecture, mainly due to their highly robust background—including low pH tolerance. Results In this work, we pioneer the use of QTL mapping to uncover the genetic basis that confers to the industrial strain Pedra-2 (PE-2) acidic tolerance during growth at low pH. First, we developed a fluorescence-based high-throughput approach to collect a large number of haploid cells using flow cytometry. Then, we were able to apply a bulk segregant analysis to solve the genetic basis of low pH resistance in PE-2, which uncovered a region in chromosome X as the major QTL associated with the evaluated phenotype. A reciprocal hemizygosity analysis revealed the allele GAS1, encoding a β-1,3-glucanosyltransferase, as the casual variant in this region. The GAS1 sequence alignment of distinct S. cerevisiae strains pointed out a non-synonymous mutation (A631G) prevalence in wild-type isolates, which is absent in laboratory strains. We further showcase that GAS1 allele swap between PE-2 and a low pH-susceptible strain can improve cell viability on the latter of up to 12% after a sulfuric acid wash process. Conclusion This work revealed GAS1 as one of the main causative genes associated with tolerance to growth at low pH in PE-2. We also showcase how GAS1PE-2 can improve acid resistance of a susceptible strain, suggesting that these findings can be a powerful foundation for the development of more robust and acid-tolerant strains. Our results collectively show the importance of tailored industrial isolated strains in discovering the genetic architecture of relevant traits and its implications over productivity.

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Unravelling the complex genetic basis of growth in New Zealand silver trevally (Pseudocaranx georgianus)

10.1101/2021.10.11.463933 ◽

2021 ◽

Author(s):

Noemie Valenza-Troubat ◽

Sara Montanari ◽

Peter Ritchie ◽

Maren Wellenreuther

Keyword(s):

Qtl Mapping ◽

Complex Traits ◽

Genetic Basis ◽

Growth Traits ◽

Association Studies ◽

Snp Markers ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Powerful Approach ◽

Trait Locus

AbstractGrowth directly influences production rate and therefore is one of the most important and well-studied trait in animal breeding. However, understanding the genetic basis of growth has been hindered by its typically complex polygenic architecture. Here, we performed quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS) for 10 growth traits that were observed over two years in 1,100 F1 captive-bred trevally (Pseudocaranx georgianus). We constructed the first high-density linkage map for trevally, which included 19,861 single nucleotide polymorphism (SNP) markers, and discovered eight QTLs for height, length and weight on linkage groups 3, 14 and 18. Using GWAS, we further identified 113 SNP-trait associations, uncovering 10 genetic hot spots involved in growth. Two of the markers found in the GWAS co-located with the QTLs previously mentioned, demonstrating that combining QTL mapping and GWAS represents a powerful approach for the identification and validation of loci controlling complex traits. This is the first study of its kind for trevally. Our findings provide important insights into the genetic architecture of growth in this species and supply a basis for fine mapping QTLs, marker-assisted selection, and further detailed functional analysis of the genes underlying growth in trevally.

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