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Biomedical subjects

Michael Lachmann

Publications and source records attributed to Michael Lachmann.

12 recordsLinked to original sources
PubMed2006

Functionality of intergenic transcription: an evolutionary comparison.

Although a large proportion of human transcription occurs outside the boundaries of known genes, the functional significance of this transcription remains unknown. We have compared the expression patterns of known genes as well as intergenic transcripts within the ENCODE regions between humans and chimpanzees in brain, heart, testis, and lymphoblastoid cell lines. We find that intergenic transcripts show patterns of tissue-specific conservation of their expression, which are comparable to exonic transcripts of known genes. This suggests that intergenic transcripts are subject to functional constraints that restrict their rate of evolutionary change as well as putative positive selection to an extent comparable to that of classical protein-coding genes. In brain and testis, we find that part of this intergenic transcription is caused by widespread use of alternative promoters. Further, we find that about half of the expression differences between humans and chimpanzees are due to intergenic transcripts.

Animals↗
PubMed2006

Evolution of primate gene expression.

It has been suggested that evolutionary changes in gene expression account for most phenotypic differences between species, in particular between humans and apes. What general rules can be described governing expression evolution? We find that a neutral model where negative selection and divergence time are the major factors is a useful null hypothesis for both transcriptome and genome evolution. Two tissues that stand out with regard to gene expression are the testes, where positive selection has exerted a substantial influence in both humans and chimpanzees, and the brain, where gene expression has changed less than in other organs but acceleration might have occurred in human ancestors.

Animals↗
PubMed2005

Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees.

The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.

Adult↗
PubMed2005

Evolution of genetic potential.

Organisms employ a multitude of strategies to cope with the dynamical environments in which they live. Homeostasis and physiological plasticity buffer changes within the lifetime of an organism, while stochastic developmental programs and hypermutability track changes on longer time-scales. An alternative long-term mechanism is "genetic potential"--a heightened sensitivity to the effects of mutation that facilitates rapid evolution to novel states. Using a transparent mathematical model, we illustrate the concept of genetic potential and show that as environmental variability decreases, the evolving population reaches three distinct steady state conditions: (1) organismal flexibility, (2) genetic potential, and (3) genetic robustness. As a specific example of this concept we examine fluctuating selection for hydrophobicity in a single amino acid. We see the same three stages, suggesting that environmental fluctuations can produce allele distributions that are distinct not only from those found under constant conditions, but also from the transient allele distributions that arise under isolated selective sweeps.

Journal Article↗
PubMed2005

Quasispecies made simple.

Quasispecies are clouds of genotypes that appear in a population at mutation-selection balance. This concept has recently attracted the attention of virologists, because many RNA viruses appear to generate high levels of genetic variation that may enhance the evolution of drug resistance and immune escape. The literature on these important evolutionary processes is, however, quite challenging. Here we use simple models to link mutation-selection balance theory to the most novel property of quasispecies: the error threshold-a mutation rate below which populations equilibrate in a traditional mutation-selection balance and above which the population experiences an error catastrophe, that is, the loss of the favored genotype through frequent deleterious mutations. These models show that a single fitness landscape may contain multiple, hierarchically organized error thresholds and that an error threshold is affected by the extent of back mutation and redundancy in the genotype-to-phenotype map. Importantly, an error threshold is distinct from an extinction threshold, which is the complete loss of the population through lethal mutations. Based on this framework, we argue that the lethal mutagenesis of a viral infection by mutation-inducing drugs is not a true error catastophe, but is an extinction catastrophe.

Genes, Lethal↗
PubMed2004

The disadvantage of combinatorial communication.

Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems.

Animal Communication↗
PubMed2004

A neutral model of transcriptome evolution.

Microarray technologies allow the identification of large numbers of expression differences within and between species. Although environmental and physiological stimuli are clearly responsible for changes in the expression levels of many genes, it is not known whether the majority of changes of gene expression fixed during evolution between species and between various tissues within a species are caused by Darwinian selection or by stochastic processes. We find the following: (1) expression differences between species accumulate approximately linearly with time; (2) gene expression variation among individuals within a species correlates positively with expression divergence between species; (3) rates of expression divergence between species do not differ significantly between intact genes and expressed pseudogenes; (4) expression differences between brain regions within a species have accumulated approximately linearly with time since these regions emerged during evolution. These results suggest that the majority of expression differences observed between species are selectively neutral or nearly neutral and likely to be of little or no functional significance. Therefore, the identification of gene expression differences between species fixed by selection should be based on null hypotheses assuming functional neutrality. Furthermore, it may be possible to apply a molecular clock based on expression differences to infer the evolutionary history of tissues.

Animals↗
PubMed2004

Regional patterns of gene expression in human and chimpanzee brains.

We have analyzed gene expression in various brain regions of humans and chimpanzees. Within both human and chimpanzee individuals, the transcriptomes of the cerebral cortex are very similar to each other and differ more between individuals than among regions within an individual. In contrast, the transcriptomes of the cerebral cortex, the caudate nucleus, and the cerebellum differ substantially from each other. Between humans and chimpanzees, 10% of genes differ in their expression in at least one region of the brain. The majority of these expression differences are shared among all brain regions. Whereas genes encoding proteins involved in signal transduction and cell differentiation differ significantly between brain regions within individuals, no such pattern is seen between the species. However, a subset of genes that show expression differences between humans and chimpanzees are distributed nonrandomly across the genome. Furthermore, genes that show an elevated expression level in humans are statistically significantly enriched in regions that are recently duplicated in humans.

Adult↗
PubMed2003

The Red King effect: when the slowest runner wins the coevolutionary race.

Mutualisms provide benefits to those who participate in them. As a mutualism evolves, how will these benefits come to be allocated among the participants? We approach this question by using evolutionary game theory and explore the ways in which the coevolutionary process determines the allocation of benefits in mutualistic interactions. Motivated by the Red Queen theory, which states that coevolutionary processes favor rapid rates of evolution, we pay particular attention to the role of evolutionary rates in the establishment of mutualism and the partitioning of benefits among mutualist partners. We find that, contrary to the Red Queen, in mutualism evolution the slowly evolving species is likely to gain a disproportionate share of the benefits. Moreover, population structure serves to magnify the advantage to the slower species.

Animals↗
PubMed2002

Separating equilibria in continuous signalling games.

Much of the literature on costly signalling theory concentrates on separating equilibria of continuous signalling games. At such equilibria, every signaller sends a distinct signal, and signal receivers are able to exactly infer the signaller's condition from the signal sent. In this paper, we introduce a vector-field solution method that simplifies the process of solving for separating equilibria. Using this approach, we show that continuous signalling games can have low-cost separating equilibria despite conflicting interests between signaller and receiver. We find that contrary to prior arguments, honesty does not require wasteful signals. Finally, we examine signalling games in which different signallers have different minimal-cost signals, and provide a mathematical justification for the argument that even non-signalling traits will be exaggerated beyond their phenotypic optimum when they are used by other individuals to judge condition or quality.

Communication↗