The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform

Christopher J. Marx - One of the best experts on this subject based on the ideXlab platform.

  • sign epistasis limits evolutionary trade offs at the confluence of single and multi carbon metabolism in methylobacterium extorquens am1
    Evolution, 2014
    Co-Authors: Sean M Carroll, Mingchun Lee, Christopher J. Marx
    Abstract:

    Adaptation of one set of traits is often accompanied by attenuation of traits important in other selective environments, leading to fitness trade-offs. The mechanisms that either promote or prevent the emergence of trade-offs remain largely unknown, and are difficult to discern in most systems. Here, we investigate the basis of trade-offs that emerged during experimental evolution of Methylobacterium extorquens AM1 to distinct growth substrates. After 1500 generations of adaptation to a multi-carbon substrate, succinate (S), many lineages had lost the ability to use one-carbon compounds such as methanol (M), generating a mixture of M(+) and M(-) evolved phenotypes. We show that trade-offs in M(-) strains consistently arise via antagonistic pleiotropy through recurrent selection for loss-of-function mutations to ftfL (Formate-Tetrahydrofolate Ligase), which improved growth on S while simultaneously eliminating growth on M. But if loss of FtfL was beneficial, why were M trade-offs not found in all populations? We discovered that eliminating FtfL was not universally beneficial on S, as it was neutral or even deleterious in certain evolved lineages that remained M(+) . This suggests that sign epistasis with earlier arising mutations prevented the emergence of mutations that drove trade-offs through antagonistic pleiotropy, limiting the evolution of metabolic specialists in some populations.

  • purification of the Formate Tetrahydrofolate Ligase from methylobacterium extorquens am1 and demonstration of its requirement for methylotrophic growth
    Journal of Bacteriology, 2003
    Co-Authors: Christopher J. Marx, Markus Laukel
    Abstract:

    The serine cycle methylotroph Methylobacterium extorquens AM1 contains two pterin-dependent pathways for C1 transfers, the Tetrahydrofolate (H4F) pathway and the tetrahydromethanopterin (H4MPT) pathway, and both are required for growth on C1 compounds. With the exception of Formate-Tetrahydrofolate Ligase (FtfL, alternatively termed formyl-H4F synthetase), all of the genes encoding the enzymes comprising these two pathways have been identified, and the corresponding gene products have been purified and characterized. We present here the purification and characterization of FtfL from M. extorquens AM1 and the confirmation that this enzyme is encoded by an ftfL homolog identified previously through transposon mutagenesis. Phenotypic analyses of the ftfL mutant strain demonstrated that FtfL activity is required for growth on C1 compounds. Unlike mutants defective for the H4MPT pathway, the ftfL mutant strain does not exhibit phenotypes indicative of defective formaldehyde oxidation. Furthermore, the ftfL mutant strain remained competent for wild-type conversion of [14C]methanol to [14C]CO2. Collectively, these data confirm our previous presumptions that the H4F pathway is not the key formaldehyde oxidation pathway in M. extorquens AM1. Rather, our data suggest an alternative model for the role of the H4F pathway in this organism in which it functions to convert Formate to methylene H4F for assimilatory metabolism.

Mingchun Lee - One of the best experts on this subject based on the ideXlab platform.

  • sign epistasis limits evolutionary trade offs at the confluence of single and multi carbon metabolism in methylobacterium extorquens am1
    Evolution, 2014
    Co-Authors: Sean M Carroll, Mingchun Lee, Christopher J. Marx
    Abstract:

    Adaptation of one set of traits is often accompanied by attenuation of traits important in other selective environments, leading to fitness trade-offs. The mechanisms that either promote or prevent the emergence of trade-offs remain largely unknown, and are difficult to discern in most systems. Here, we investigate the basis of trade-offs that emerged during experimental evolution of Methylobacterium extorquens AM1 to distinct growth substrates. After 1500 generations of adaptation to a multi-carbon substrate, succinate (S), many lineages had lost the ability to use one-carbon compounds such as methanol (M), generating a mixture of M(+) and M(-) evolved phenotypes. We show that trade-offs in M(-) strains consistently arise via antagonistic pleiotropy through recurrent selection for loss-of-function mutations to ftfL (Formate-Tetrahydrofolate Ligase), which improved growth on S while simultaneously eliminating growth on M. But if loss of FtfL was beneficial, why were M trade-offs not found in all populations? We discovered that eliminating FtfL was not universally beneficial on S, as it was neutral or even deleterious in certain evolved lineages that remained M(+) . This suggests that sign epistasis with earlier arising mutations prevented the emergence of mutations that drove trade-offs through antagonistic pleiotropy, limiting the evolution of metabolic specialists in some populations.

Sean M Carroll - One of the best experts on this subject based on the ideXlab platform.

  • sign epistasis limits evolutionary trade offs at the confluence of single and multi carbon metabolism in methylobacterium extorquens am1
    Evolution, 2014
    Co-Authors: Sean M Carroll, Mingchun Lee, Christopher J. Marx
    Abstract:

    Adaptation of one set of traits is often accompanied by attenuation of traits important in other selective environments, leading to fitness trade-offs. The mechanisms that either promote or prevent the emergence of trade-offs remain largely unknown, and are difficult to discern in most systems. Here, we investigate the basis of trade-offs that emerged during experimental evolution of Methylobacterium extorquens AM1 to distinct growth substrates. After 1500 generations of adaptation to a multi-carbon substrate, succinate (S), many lineages had lost the ability to use one-carbon compounds such as methanol (M), generating a mixture of M(+) and M(-) evolved phenotypes. We show that trade-offs in M(-) strains consistently arise via antagonistic pleiotropy through recurrent selection for loss-of-function mutations to ftfL (Formate-Tetrahydrofolate Ligase), which improved growth on S while simultaneously eliminating growth on M. But if loss of FtfL was beneficial, why were M trade-offs not found in all populations? We discovered that eliminating FtfL was not universally beneficial on S, as it was neutral or even deleterious in certain evolved lineages that remained M(+) . This suggests that sign epistasis with earlier arising mutations prevented the emergence of mutations that drove trade-offs through antagonistic pleiotropy, limiting the evolution of metabolic specialists in some populations.

Markus Laukel - One of the best experts on this subject based on the ideXlab platform.

  • purification of the Formate Tetrahydrofolate Ligase from methylobacterium extorquens am1 and demonstration of its requirement for methylotrophic growth
    Journal of Bacteriology, 2003
    Co-Authors: Christopher J. Marx, Markus Laukel
    Abstract:

    The serine cycle methylotroph Methylobacterium extorquens AM1 contains two pterin-dependent pathways for C1 transfers, the Tetrahydrofolate (H4F) pathway and the tetrahydromethanopterin (H4MPT) pathway, and both are required for growth on C1 compounds. With the exception of Formate-Tetrahydrofolate Ligase (FtfL, alternatively termed formyl-H4F synthetase), all of the genes encoding the enzymes comprising these two pathways have been identified, and the corresponding gene products have been purified and characterized. We present here the purification and characterization of FtfL from M. extorquens AM1 and the confirmation that this enzyme is encoded by an ftfL homolog identified previously through transposon mutagenesis. Phenotypic analyses of the ftfL mutant strain demonstrated that FtfL activity is required for growth on C1 compounds. Unlike mutants defective for the H4MPT pathway, the ftfL mutant strain does not exhibit phenotypes indicative of defective formaldehyde oxidation. Furthermore, the ftfL mutant strain remained competent for wild-type conversion of [14C]methanol to [14C]CO2. Collectively, these data confirm our previous presumptions that the H4F pathway is not the key formaldehyde oxidation pathway in M. extorquens AM1. Rather, our data suggest an alternative model for the role of the H4F pathway in this organism in which it functions to convert Formate to methylene H4F for assimilatory metabolism.

Sm Carroll - One of the best experts on this subject based on the ideXlab platform.

  • Sign epistasis limits evolutionary trade-offs at the confluence of single- and multi-carbon metabolism in Methylobacterium extorquens AM1
    'Wiley', 2014
    Co-Authors: Cj Marx, Mc Lee, Sm Carroll
    Abstract:

    Adaptation of one set of traits is often accompanied by attenuation of traits important in other selective environments, leading to fitness trade-offs. The mechanisms that either promote or prevent the emergence of trade-offs remain largely unknown, and are difficult to discern in most systems. Here, we investigate the basis of trade-offs that emerged during experimental evolution of Methylobacterium extorquens AM1 to distinct growth substrates. After 1500 generations of adaptation to a multi-carbon substrate, succinate (S), many lineages had lost the ability to use one-carbon compounds such as methanol (M), generating a mixture of M(+) and M(-) evolved phenotypes. We show that trade-offs in M(-) strains consistently arise via antagonistic pleiotropy through recurrent selection for loss-of-function mutations to ftfL (Formate-Tetrahydrofolate Ligase), which improved growth on S while simultaneously eliminating growth on M. But if loss of FtfL was beneficial, why were M trade-offs not found in all populations? We discovered that eliminating FtfL was not universally beneficial on S, as it was neutral or even deleterious in certain evolved lineages that remained M(+) . This suggests that sign epistasis with earlier arising mutations prevented the emergence of mutations that drove trade-offs through antagonistic pleiotropy, limiting the evolution of metabolic specialists in some populations.link_to_subscribed_fulltex