Research in biosciences
I work on quantitative biological problems
associated with recombination and meiosis on the one hand and
on the modeling of intra-cellular networks on the other.
Publications in reverse chronological order:
X. Raffoux, M. Bourge, F. Dumas, O.C. Martin and M. Falque,
Role of cis, trans, and inbreeding effects on meiotic recombination in Saccharomyces cerevisiae,
Genetics (2018), DOI 10.1534/genetics.118.301644
We measure recombination rates in hybrids between SK1 and a total of 26 S. cerevisiae strains from different geographic origins and habitats. Our overall results indicate that recombination rate is increasingly positively correlated with sequence similarity between homologs (i) in DNA double-strand break rich regions within intervals, (ii) in entire intervals, and (iii) at the whole genome scale. Therefore, these correlations cannot be explained by cis-effects only. We estimated that cis and trans effects explained respectively 38% and 17% of the variance of recombination rates.
D. Collot, T. Nidelet, J. Ramsayer, O.C. Martin, S. Méléard, C. Dillmann, D. Sicard and J. Legrand,
Feedback between environment and traits under selection in a seasonal environment: consequences for experimental evolution,
Proc. R. Soc. B, 285(1876), 20180284 (2018), DOI 10.1098/rspb.2018.0284.
Recurrent batch cultures form a seasonal environment where different phases repeat periodically. We developed a mathematical model to understand which traits of yeasts in such cultures are under selection and what is the role of the environment in eco-evolutionary feedbacks. We showed that two kinds of traits are under selection: life-history traits, related to growth and mortality, and also transition traits, related to the ability to react to environmental changes.
X. Raffoux, M. Bourge, F. Dumas, O.C. Martin and M. Falque,
High-throughput measurement of recombination rates and genetic interference in Saccharomyces cerevisiae,
Yeast, 35(6), 431--442 (2018), DOI 10.1002/yea.3315.
We develop a high-throughput and low-cost method to measure recombination rates and crossover patterning (including interference) in large populations of the budding yeast Saccharomyces cerevisiae. Recombination and interference were analysed by flow cytometry, which allows time-consuming steps such as tetrad microdissection or spore growth to be avoided.
S. Grigolon, B. Bravi and O.C. Martin,
Responses to auxin signals: an operating principle for dynamical sensitivity yet high resilience,
R. Soc. open sci. 2018 5 172098; DOI: 10.1098/rsos.172098.
Plants depend on the signaling of the phytohormone auxin for their development and for responding to environmental perturbations. The associated biomolecular signaling network involves a negative feedback at the level of the Aux/IAA proteins which mediate the influence of auxin (the signal) on the ARF transcription factors (the drivers of the response). To probe the role of this feedback, we consider alternative in silico signaling networks implementing different operating principles. By a comparative analysis, we find that the presence of a negative regulatory feedback loop allows the system to have a far larger sensitivity in its dynamical response to auxin. At the same time, this sensitivity does not prevent the system from being highly resilient. Given this insight, we reconsider previously published models and build a new quantitative and calibrated biomolecular model of auxin signaling.
The model is available on the BIOMODELS website under the name
A. Samal and O.C. Martin,
Haldane, Waddington and recombinant inbred lines: extension of their work to any number of genes,
Journal of Genetics, DOI:10.1007/s12041-017-0837-0 (2017).
We revisit the multi-locus probabilities of homozygous genotypes arising in recombinant
inbred lines and treated for 2 and 3 loci by Haldane and Waddington (H&W) in 1931.
From historical perspective, it is
interesting to note that the father of statistical genetics, R.A. Fisher, also had strong interests in inbreeding, introducing his own approach based on junctions. It is only now with our mathematical break-through allowing the treatment of many loci that the much greater power of the H&W approach transpires over the one proned by Fisher.
A. Pele, M. Falque, ..., O.C. Martin, M. Rousseau-Gueutin and A-M. Chevre,
Amplifying recombination genome-wide and reshaping crossover landscapes in Brassicas,
PLOS Genetics, 13(5): e1006794 (2017).
Press coverage (in French).
During meiosis, the reciprocal exchanges between the homologous chromosomes due to crossovers (COs) ensure their proper segregation as well as the generation of diversity. However, the number of COs is limited and their location is heterogeneous along chromosomes. A major challenge is to overcome these constraints for enhancing the genetic shuffling of alleles. This work demonstrates that it is possible to do so in Brassica hybrids obtained by manual crossings, combining a complete set of homologous chromosomes and a haploid set provided by a related species. By studying large segregating populations, we find that in allotriploid Brassica hybrids, more COs are formed all along the homologous chromosomes, especially in regions usually deprived of COs, compared to diploids. These results offer the opportunity for geneticists and plant breeders to dramatically enhance the generation of new diversity.
S.R. Hosseini, O.C. Martin and A Wagner,
Phenotypic innovation through recombination in genome-scale metabolic networks,
Proc. R. Soc. B 283 (1839), 20161536 (2016).
We show that recombination is much more likely to create novel metabolic abilities than random changes in chemical reactions of a metabolic network. We also find that phenotypic innovation is more likely when recombination occurs between parents that are genetically closely related, phenotypically highly diverse, and viable on few rather than many carbon sources.
A. Henry and O.C. Martin,
Short relaxation times but long transient times in both simple and complex reaction networks,
J. R. Soc. Interface 13, 20160388 (2016).
By mathematical analysis of simple reaction networks, we pin-point the reason why the standard relaxation time does not provide relevant information on the potentially long transient times of typical infinitesimal perturbations.
O.C. Martin, A. Krzywicki and M. Zagorski,
Drivers of structural features in gene regulatory networks: From biophysical constraints to
Phys. Life Rev. (2016).
The logic of a regulatory program can sometimes be guessed at by examining the network
of influences amongst its components. Studies of gene regulatory networks
have unveiled structural features ranging from broad distributions of out-degrees
to recurrent "motifs", that is small subgraphs having a specific pattern of
interactions. We review here different approaches to understanding what factors drive such
structuring and show how selection for phenotypes, i.e., the function of
a regulatory network, can shape the structure of the network.
M. Mori, T. Hwa, O.C. Martin, A. De Martino and E. Marinari,
Constrained Allocation Flux Balance Analysis,
PLOS Comput Biol 12(6): e1004913 (2016).
We introduce a computational genome-scale framework which
provides a quantitative approach to balancing the trade-off between growth and its
associated biosynthetic costs at genome-scale, without the burden of tuning many inaccessible parameters.
G.K. Sidhu, C. Fang, M.A. Olson, M. Falque, O.C. Martin,
and W.P. Pawlowski,
Recombination patterns in maize reveal limits to
PNAS (2015) 1514265112.
During meiosis, chromosomes exchange segments in a process of crossing-over. The crossover number is tightly regulated so that at least one crossover (but not many more) is formed per chromosome. The process of crossover homeostasis is thought to play a major role in this regulation by ensuring a stable crossover number even if the number of DNA breaks that initiate crossover formation varies. However, we found that, in maize, the crossover number changes with the number of DNA breaks, suggesting that different species exhibit different crossover control mechanisms. Plant breeders rely on recombination to create new combinations of alleles. Our data suggest that increasing recombination rates in plants may be accomplished by increasing the number of DNA breaks.
A. Samal, O.C. Martin,
Statistical physics methods provide the exact solution to a long-standing problem of genetics,
Phys. Rev. Lett. 114, 238101 (2015).
(Supplemental Material and
C source code.) Highlighted as a "Editors' choice", received press coverage in Physics Today and was
in the news of several institutions (ICTP, Italy, and
INRA, both for the
Versailles-Grignon center and
In a landmark 1931 paper, Haldane and Waddington formulated the statistical genetics problem of finding the probabilities of all different genetic outcomes when repeatedly inbreeding a plant. Those authors gave a mathematical solution when restricting the situation to just two or three genes at a time. Extending Haldane and Waddington's results to 4 or more genes has seemed unsurmountable since that seminal paper of over 80 years ago. Yet, in this work, we provide the generalization of the formulas to any number of genes. The key to our solution is the exploitation of framework equations developed by Nobel physicists Roy Glauber and Julian Schwinger. Surprisingly, the associated formulas involve only the standard four operations (addition, subtraction, multiplication and division) and can be produced automatically. These multi-variate probabilities can be included in genetic analyses while extensions of our framework may provide mathematical solutions to other interdisciplinary problems involving many variables.
S. Grigolon, P. Sollich, O.C. Martin,
Modelling the emergence of polarity patterns for the intercellular transport of auxin in plants ,
J. R. Soc. Interface (2015) 12 20141223.
The hormone auxin is actively transported throughout plants via protein machineries including the dedicated transporter known as PIN. The associated transport is ordered with nearby cells driving auxin flux in similar directions. Here, we provide a model of both the auxin transport and of the dynamics of cellular polarization based on flux sensing. Our main findings are: (i) spontaneous intracellular PIN polarization arises if PIN recycling dynamics are sufficiently nonlinear, (ii) there is no need for an auxin concentration gradient and (iii) ordered multi-cellular patterns of PIN polarization are favoured by molecular noise.
L.K. Anderson, L.D. Lohmiller, X. Tang, D.B. Hammond, L. Javernick, L. Shearer,
S. Basu-Roy, O.C. Martin, M. Falque,
Combined fluorescent and electron microscopic imaging unveils the specific properties of two classes of meiotic crossovers ,
PNAS (2014) 111 (37) 13415-13420. Highlighted
in the INRA news.
By identifying COs from each class simultaneously on tomato meiotic chromosomes, we
reveal that the two CO classes have different distributions, with class II COs enriched in short arms
and heterochromatin. Although class II CO distributions are consistent with no interference,
interference between the two pathways was detected, with suppression of close class I and class II COs.
M. Tagliaro Jahns, D. Verzon, A. Chambon, L. Pereira, M. Falque,
O.C. Martin, L. Chelysheva, M. Grelon,
Crossover Localisation Is Regulated by the Neddylation Posttranslational Regulatory Pathway,
PLOS Biology (2014) 12(8):e1001930.
Post-translational protein modification by neddylation is involved in regulating the position but not the number of crossovers during meiosis in the model plant Arabidopsis.
A. Barve, S-R. Hosseini, O.C. Martin and A. Wagner,
Historical contingency and the gradual evolution of metabolic properties in
central carbon and genome-scale metabolisms,
BMC Systems Biology (2014) 8:48.
Using a Flux Balance Analysis framework, we show that metabolism is highly evolvable, in the sense that its properties can be fine-tuned by successively altering individual reactions. Historical contingency does not strongly restrict the origin of novel metabolic phenotypes.
L. Suay, D. Zhang, ..., A.-M. Chevre,
Crossover rate between homologous chromosomes and interference are regulated by
the addition of specific unpaired chromosomes in Brassica,
New Phytologist (2014) 201 (2), 645-656.
The homologous recombination rate between A genomes in AAC hybrids of Brassica napus
is affected by the presence of the C chromosomes. By comparing the
the genetic map lengths of different hybrids, we show
for the first time that the presence of one chromosome, C9, increases significantly
the recombination rate and reduces crossover interference.
E. Bauer, M. Falque, ..., O.C. Martin and C.-C. Schoen,
Intraspecific variation of recombination rate in maize,
Genome Biology, 14:R103 (2013).
Recombination landscapes in crosses between 22 European maize inbred lines are
determined from high-density genotyping of double-haploid populations. We show that there are
significant differences and that these cannot be attributed only
to the presence of the dent and flint groups in these lines. We also analyze
crossoer interference, revealing a negative association between recombination
rate and interference strength.
S. Basu Roy, F. Gauthier, L. Giraut, C. Mezard, M. Falque and O.C. Martin,
Hot Regions of Non-Interfering Crossovers Coexist with a Non-Uniformly
Interfering Pathway in Arabidopsis thaliana,
Genetics 113.155549 (2013).
Using 1500 male and female meioses in Arabidopsis thaliana, we find that the interfering pathway has
markedly higher interference strength nu in female than male meiosis and also that male meiosis has
a higher proportion p of non-interfering crossovers. Furthermore, we test for intra-chromosomal variations
of nu and p. Our conclusion is that there are clear differences between left and right arms as well
as between central and peripheral regions. Finally, statistical tests unveil a genome-wide picture
of small scale heterogeneities, pointing to the existence of hot regions in the genome where
COs form preferentially without interference.
A. Samal and O.C. Martin
Shining fresh light on the evolution of photosynthesis,
eLife 2:e01403 (2013).
There are two types of photosynthesis, C3 and the evolutionarily more recent one, C4.
There is much interest in trying to transfer some C4 features such
as high photosynthetic efficiency and drought resistance into important
C3 crop plants such as rice. The present article is an insight
into the computational study
of Williams, Johnston, Covshoff and Hibberd who explore
how C4 plants evolved many different times from C3 ancestors. Such multiple paths
may provide strategies for genetically engineering crop plants.
A. Henry, F. Moneger, A. Samal and O.C. Martin,
Network function shapes network structure: the case of the Arabidopsis flower organ specification genetic network,
Mol. BioSyst., 9(7), 1726--1735, 2013.
In the "network function shapes network structure scenario",
we examine how the gene expression patterns of Arabidopsis flower organogenesis
shape edge usage and network motifs.
M. Zagorski, A. Krzywicki and O.C. Martin,
Edge usage, motifs and regulatory logic for cell cycling genetic networks,
Phys. Rev. E 87, 012727, 2013.
The cell cycle is a tightly controlled process, yet its underlying
genetic network shows marked differences across species.
Which of the associated structural features follow solely
from the ability to impose the appropriate gene expression
patterns? We tackle this question in silico, focusing
on three cell cycle profiles coming from baker's yeast, fission
yeast and mammals.
M.W. Ganal, ..., O.C. Martin and M. Falque,
A Large Maize (Zea mays L.) SNP Genotyping Array: Development and Germplasm Genotyping, and Genetic Mapping to Compare with the B73 Reference Genome,
PLoS ONE 6(12): e28334 (2011).
We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. Two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped from which two high density linkage maps with 20,913 and 14,524 markers respectively were generated. These maps were compared to the current B73 assembly, revealing some non-syntenic markers as well as exceptions to colinearity.
Z. Burda, A. Krzywicki, O.C. Martin and M. Zagorski,
Motifs emerge from function in model gene regulatory networks,
PNAS 108 (42) 17263-17268, 2011.
Gene regulatory networks arise in all living cells, allowing the
control of gene expression patterns. The study of their topology
has revealed that certain subgraphs of interactions or "motifs" appear
at anomalously high frequencies. We show here that this phenomenon
may emerge because of the functions carried out by these networks.
L. Giraut, M. Falque, J. Drouaut, L. Pereira, O.C. Martin and C. Mezard,
Genome-wide crossover distribution in Arabidopsis thaliana
meiosis reveals sex specific patterns along chromosomes,
PLoS Genetics 7(11): e1002354, 2011.
We report a detailed, genome-wide characterization of the
rate and localization of COs in Arabidopsis thaliana, in male and
female meiosis and also perform an analysis of interference.
O.C. Martin and F. Hospital
Distribution of parental genome blocks in recombinant inbred lines,
Genetics 189:645-654, 2011.
Exploiting renewal processes and enumerations of random walks on hypercubes, we
derive statistical properties of the mosaic genomes arising in RILS. Particular
attention is given to the distribution of number and of length of Identical by Descent (IBD)
blocks for both SSD and SIB RILs.
A. Samal, A. Wagner and O.C. Martin
Environmental versatility promotes modularity in
genome-scale metabolic networks,
BMC Systems Biology 5:135 2011.
We consider in silico metabolic genotypes capable of growing on various media
based on the Flux Balance Analysis mapping from genotype to phenotype.
We find that imposing growth capabilities in more and more
media leads to enhanced modularity of the underlying metabolic networks.
A. Samal and O.C. Martin
Randomizing genome-scale metabolic networks,
PLoS One 6(7): e22295 2011.
To make patent unexpected structures in biological networks, practice
is to compare experimental networks to randomized in silico
networks for which the edges have been shuffled.
However this makes no sense in the case of metabolic networks because
it does not conserve atomic species. We show how to use a different
randomization algorithm which has the property of using only
valid biochemical reactions in all in silico metabolic networks.
C. Espinosa-Soto, O.C. Martin and A. Wagner
Phenotypic robustness can increase phenotypic variability after
nongenetic perturbations in gene regulatory circuits,
J. Evol. Bio. 24(6), 1284 2011.
Within a transcriptional regulation model of gene expression, we examine
the putative tradeoff between phenotypic robustness and phenotypic diversity
under environmental changes. Interestingly, in some circumstances, the tradeoff
can become a positive correlation.
F. Gauthier, O.C. Martin and M. Falque
CODA (CrossOver Distribution Analyzer): quantitative characterization of
crossover position patterns along chromosomes,
BMC Bioinformatics 2011, 12:27 2011.
This note provides a software system for analyzing crossover datasets
using either one or two pathways of formation of those crossovers, allowing
the interfering pathway to be specified either by
the Gamma model or by the Beam-film model.
The user-friendly interface also provides simulational capabilities.
C. Espinosa-Soto, O.C. Martin and A. Wagner
Phenotypic plasticity can facilitate adaptive evolution
in gene regulatory circuits,
BMC Evolutionary Biology 11:5 2011.
Within a model of gene regulation connecting genotypes to phenotypes, we consider
the set of all Gene Regulatory Networks (GRNs) having a given phenotypic
behavior. In such a framework, we find that a GRN having phenotypic plasticity
has a greater chance under mutation of producing new phenotypes.
P. Sulc, A. Wagner and O.C. Martin
Quantifying Slow Evolutionary Dynamics in RNA Fitness Landscapes,
Journal of Bioinformatics and Computational Biology, Vol. 8, No. 6, 2010.
We re-examine the evolutionary dynamics of RNA secondary structures
under directional selection towards an optimum RNA structure. We
find punctuated equilibria that lead to a very slow approach
to the optimum, following on average an inverse power of the
evolutionary time. In addition, our study of the trajectories
shows that the out-of-equilibrium effects due to the evolutionary
process are very weak. In particular, the distribution of
genotypes is close to that arising during equilibrium stabilizing
selection. As a consequence, the evolutionary dynamics leave
almost no measurable out-of-equilibrium trace, only the transition
genotypes (close to the border between different periods of
stasis) have atypical mutational properties.
Z. Burda, A. Krzywicki, O.C. Martin and M. Zagorski,
Distribution of essential interactions in model gene regulatory networks
under mutation-selection balance,
Phys. Rev. E 82, 011908 (2010).
Gene regulatory networks typically have low in-degrees and
broad distributions for the out-degree. What mechanisms might be
responsible for these properties? Starting with an accepted framework
of the binding of transcription factors to DNA, we consider a
simple model of gene regulatory dynamics. There, we show that
selection for a target expression pattern leads to the
emergence of minimum connectivities compatible with the
selective constraint. "Functionality" is concentrated on
a sparse number of interactions as measured for instance
by their essentiality. Furthermore, we find that
mutations of the transcription factors drive the
networks to have broad out-degrees. Finally, these classes
of models are evolvable, i.e. significantly different genotypes
can emerge gradually under mutation-selection balance.
A. Samal, J.F. Mathias Rodrigues, J. Jost, O.C. Martin and A. Wagner
Genotype networks in metabolic reaction spaces,
BMC Syst. Bio. 4, 30 2010.
We use MCMC to sample in silico the metabolic genotypes capable of growing on
given media according to Flux Balance Analysis. The associated set of genotypes
belongs to a network which we show spans much of all genotypic space
and which essentially forms one giant connected component.
I. Junier, O. Martin, F. Kepes
Spatial and Topological Organization of DNA Chains
Induced by Gene Co-localization,
PLoS Comput Biol 6(2): e1000678, 2010.
Chromosome conformations are investigated in silico based on a thermodynamic
modeling of a polymer. If transcription factors are multi-valent, they will
tend to cluster their targets and thereby induce organized phases in which DNA
looping plays a key role.
M. Falque, L.K. Anderson, S. Stack and O.C. Martin,
Two pathways of meiotic crossovers coexist in maize,
The Plant Cell 21(12): 3915-3925 (2009).
Based on electron microscopy imaging of late nodules in pachytene which
are markers of crossovers, we perform a two-pathway analysis on the
patterns of occurrences of crossovers in maize. The abundance of
nearby crossovers allows us to show that the second (non-interfering)
pathway is present and provides around 20% of the crossovers for each
of the chromosomes. Data analyzed here has kindly been provided by Lorrie Anderson for research
purposes only and if you do publish work based on these data cite both this 2009 paper and her
original 2003 paper (see instructions at top of this Excel
O.C. Martin and A. Wagner,
Effects of Recombination on Complex Regulatory Circuits,
Genetics 183: 673-684 (2009).
Mutation and recombination are the two main forces generating genetic
variation. Most of this variation may be deleterious. Because
recombination can reorganize entire genes and genetic circuits, it may
have much greater consequences than point mutations. We here explore
the effects of recombination on models of transcriptional regulation
circuits that play important roles in embryonic development. We show
that recombination has weaker deleterious effects on the expression
phenotypes of these circuits than mutations.
C. Saintenac, M. Falque, O.C. Martin. E. Paux, C. Feuillet and P. Sourdille,
Detailed Recombination Studies Along Chromosome 3B Provide New Insights
on Crossover Distribution in Wheat (Triticum aestivum L.)
Genetics 181, 393-403 (2009).
In wheat (Triticum aestivum L.), the crossover (CO) frequency increases
gradually from the centromeres to the telomeres. However, little is known
about the factors affecting both the distribution and the intensity of
recombination along this gradient. To investigate this, we studied in
detail the pattern of CO along chromosome 3B of bread wheat. A dense
reference genetic map comprising 102 markers homogeneously distributed
along the chromosome was compared to a physical deletion map. Most of the
COs (90%) occurred in the distal subtelomeric regions covering 40%
of the chromosome. About 27% of the proximal regions surrounding the
centromere showed a very weak CO frequency with only three COs found in
the 752 gametes studied. Furthermore, the intensity of
interference was assessed for the first time in wheat using a Gamma
model. The results showed m values of 1.2 for male recombination and 3.5
for female recombination, pointing to positive interference along wheat
T. Jorg, O.C. Martin and A. Wagner,
Neutral network sizes of biological RNA molecules can be computed and
are not atypically small, BMC Bioinformatics, 9:464 (2008).
Neutral networks or sets consist of all genotypes with a given
phenotype. The size and structure of these sets has a strong influence
on a biological system's evolutionary properties. Here we introduce a
generalized Monte Carlo approach that can quantitatively measure neutral set sizes in
huge spaces. The method is general and applicable to many
problems where one has to estimate rare objects. We apply our
method to the genotype-to-phenotype
mapping of RNA molecules, and show that it can reliably measure
neutral set sizes for molecules up to 100 bases, a feat far
beyond what has been done previously.
O.C. Martin and A. Wagner,
Multifunctionality and robustness tradeoffs in model genetic circuits,
Biophysical Journal 94:2927-2937 (2008).
Most genetic circuits have more than one function. Does the need
to carry out more than one function severely constrain network
architecture? We find that robustness tradeoffs between several
functions do not exist in model regulatory networks, and that
each function can acquire high robustness through gradual Darwinian
D.M. de Vienne, T. Giraud and O.C. Martin,
A congruence index for testing topological similarity between
trees, Bioinformatics 23(23):3119-3124 (2007).
Our index is computationally efficient and allows for computing p-values
for very large trees.
S. Ciliberti, O.C. Martin and A. Wagner,
Innovation and robustness in complex
regulatory gene networks,
PNAS 104, 13591-13596 (2007).
Innovation is the driving force of long term evolution, but robustness
provides for short term enhancement of survival. What allows these
two contradictory forces to coexist? We show that cryptic genetic
variability (canalization), a principle at work in molecular networks
but also in other biological systems, allows for high levels of innovation
even within robust populations. This organismal principle is investigated
quantitatively using a model of regulatory gene networks.
J. Drouaud, R. Mercier, L. Chelysheva, A. Berard, M. Falque, O. Martin,
V. Zanni, D. Brunel, and C. Mezard,
Sex-Specific Crossover Distributions and Variations in Interference
Level along Arabidopsis thaliana Chromosome 4,
PLoS Genet. 3(6): e106 (2007).
We determined the crossover distribution along the Arabidopsis thaliana
Chromosome 4 (18 Mb) in male and female meiosis, giving lengths of
88 cM and 52 cM, respectively. This difference is remarkably parallel
to that between the synaptonemal
complex lengths meiocytes by immunolabeling of
ZYP1. From these data we performed a detailed analysis of crossover interference,
and in particular find that the interference level
varies significantly along the chromosome in male meiosis and is
correlated to physical distance.
Sumedha, O.C. Martin and A. Wagner,
New structural variation in evolutionary searches of RNA neutral
networks, BioSystems 90, 475--485 (2007).
An RNA neutral network is a computationally accessible
realization of a genotype to phenotype map. Evolutionary
innovation is facilitated by the connectivity of such networks.
We show that both biological and random structures share
a high rate of innovation. Furthermore, genotypes of high robustness
have a long lasting suppressive effect on the rate of innovation in their
M. Falque, R. Mercier, C. Mezard, D. de Vienne, and O.C. Martin,
Patterns of recombination and MLH1 foci density along mouse chromosomes:
modeling effects of interference and obligate chiasma,
Genetics 176(3), 1453-67 (2007).
We consider a new model to incorporate the known biological feature of
"obligate chiasma" whereby in most organisms each bivalent almost always
has at least one crossover. Our model provides a better fit
to experimental data as compared to the standard chi-square model.
It also predicts an enhancement of the recombination rate near
Sumedha, O.C. Martin and L. Peliti,
Selection and population size effects in evolutionary dynamics,
J. Stat. Mech. P05011 (2007).
We study evolutionary population dynamics subject to selective pressures, focusing
on spread and neutrality.
In the presence of drift, these observables depend mainly on the product M mu, M
being the population size and mu the mutation rate, while corrections
to this scaling go as 1/M. Such corrections can be quite large in the
presence of selection if there are barriers in the fitness landscape.
Finally, we show that, by manipulating drift, the M mu
scaling can be modified to a mu-independent scaling; then
the genotypic diversity in the population increases from O(\log M) to O(M).
S. Ciliberti, O.C. Martin and A. Wagner,
Robustness Can Evolve Gradually in Complex Regulatory Gene
Networks with Varying Topology,
PLoS Computational Biology 3(2), e15 (2007).
For a model of transcriptional regulation networks, we explore millions
of different network topologies to understand circuit robustness
and its Darwinian evolution.
All networks that attain a given gene expression state can be organized
into a (meta)graph that can be easily traversed by gradual changes
of circuit topology. This connectedness and evolvability of
robust networks may be a general organizational principle of
all biological systems.
C. Wolfrom, O. Martin, M. Laurent, J. Deschatrette,
Sinusoidal swinging dynamics of the telomere repair and cell
growth activation functions of telomerase in rat liver cancer cells,
FEBS Letters, v581(1), 125--130 (2007).
Telomerase is a multi-molecular complex of reverse transcriptase, RNA
template, and regulatory proteins. It has two known functions: catalysis of
the addition of [TTAGGG] repeats to telomeric DNA and the activation of
various genes controlling cell proliferation. The possible coordination of
these two functions is a key issue in understanding the growth of cancer
cells. We report long-term changes to this complex system in cancer cells, as exhibited by
specific data analysis methods. We show that the dynamics of the two
functions of telomerase are tightly linked, with a change in predominant
function every 13-14 weeks.
O.C. Martin and F. Hospital,
Two and three-locus tests for linkage analysis using
recombinant inbred lines,
Genetics 173, 451-459 (2006).
We derive the three-locus genotype frequencies arising in RIL and IRIL
and show how to use these for data analysis, e.g. for
interference and QTL detection.
B. Servin, O.C. Martin, M. Mezard and F. Hospital,
Toward a theory of marker-assisted gene pyramiding,
Genetics 168, 513-523 (2004).
We investigate the best way to combine into a single genotype a series of
target genes identified in different parents (gene pyramiding). Assuming
individuals can be selected and mated according to their genotype, the
best procedure corresponds to an optimal succession of crosses over
several generations (pedigree). Examples are given for eight target
genes, and compared to a reference genotype selection method.
- E. Guerry, O.C. Martin, H. Tricoire, R. Siebert, and L. Valentin,
A numerical study of persistence length effects on DNA
conformation in sequencing electrophoresis,
Electrophoresis 17 (1996) 1420-1424.
We perform a numerical study of the effects of persistence length
on DNA conformation in gels for sequence electrophoresis.
We show that the DNA's persistence length leads to an increase of
the chain's orientation along the electric field and to a
higher friction force.
- J. Boutet de Monvel and O.C. Martin,
Memory capacity in large idiotypic networks,
Bulletin of Mathematical Biology,
vol 57, No.1, p109-136 (1995).
We examine generalizations of the Weisbuch, De Boer, and Perelson
immune networks when the connectivity is very large and random. We find
that the memory capacity is essentially reduced to nil.
- E. Felten, O. Martin, S. Otto, and J. Hutchinson,
Multi-Scale Training of a Large Backpropagation Net,
Biol. Cybern. 62, (1990) 503-509.
We propose and test a multi-scale technique to improve the
learning properties of feed-forward neural networks.
- O. Martin, A. Odlyzko, and S. Wolfram,
Algebraic Properties of
Cellular Automata, Commun. Math. Phys. 93 (1984) 219-258.
We perform an in depth study of the limiting behavior
(fixed points and cycles) of cellular automata on a
UMR Génétique Végétale
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