Research in biosciences
My earliest work was motivated by biological analogies; at present
I am focusing on quantitative biological problems
associated with recombination and selection on the one hand and
modeling of networks on the other.
Publications in reverse chronological order:
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., 2013, DOI: 10.1039/C3MB25562J, 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 et al.,
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.
A. Samal, A. Wagner and O.C. Martin
Environmental versatility promotes modularity in
genome-scale metabolic networks,
BMC Systems Biology 5:135 2011.
A. Samal and O.C. Martin
Randomizing genome-scale metabolic networks,
PLoS One 6(7): e22295 2011.
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.
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.
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.
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 that the punctuated equilibria 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.
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.
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).
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 that represent 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. Moreover, we observed a clear decrease of CO
frequency on the distal region of the short arm. Finally, 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, suggesting 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 measure neutral set sizes in
larger 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).
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 CO interference,
and in particular find that the interference level
varies significantly along the chromosome in male meiosis and is
correlated to physical distance between crossovers.
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 dynamics subject to selective pressures, focusing
on the spread and the neutrality of the population in the steady state.
In the presence of drift these observables depend mainly on 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 reducing the strength of the drift the M mu
scaling can be modified to a mu-independent scaling; then
the genotypic diversity 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 multimolecular 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, as shown 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. The conservative behavior of
this dynamic system probably accounts for the persistent proliferation of
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
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