Michel Halbwax

Bio: Michel Halbwax is an academic researcher from Max Planck Society. The author has contributed to research in topics: Pan paniscus & Gene. The author has an hindex of 7, co-authored 10 publications receiving 494 citations. Previous affiliations of Michel Halbwax include EcoHealth Alliance.

On the diversity of malaria parasites in African apes and the origin of Plasmodium falciparum from Bonobos.

Abstract: The origin of Plasmodium falciparum, the etiological agent of the most dangerous forms of human malaria, remains controversial. Although investigations of homologous parasites in African Apes are crucial to resolve this issue, studies have been restricted to a chimpanzee parasite related to P. falciparum, P. reichenowi, for which a single isolate was available until very recently. Using PCR amplification, we detected Plasmodium parasites in blood samples from 18 of 91 individuals of the genus Pan, including six chimpanzees (three Pan troglodytes troglodytes, three Pan t. schweinfurthii) and twelve bonobos (Pan paniscus). We obtained sequences of the parasites' mitochondrial genomes and/or from two nuclear genes from 14 samples. In addition to P. reichenowi, three other hitherto unknown lineages were found in the chimpanzees. One is related to P. vivax and two to P. falciparum that are likely to belong to distinct species. In the bonobos we found P. falciparum parasites whose mitochondrial genomes indicated that they were distinct from those present in humans, and another parasite lineage related to P. malariae. Phylogenetic analyses based on this diverse set of Plasmodium parasites in African Apes shed new light on the evolutionary history of P. falciparum. The data suggested that P. falciparum did not originate from P. reichenowi of chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it subsequently colonized humans by a host-switch. Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria.

Bonobos Fall within the Genomic Variation of Chimpanzees

Abstract: To gain insight into the patterns of genetic variation and evolutionary relationships within and between bonobos and chimpanzees, we sequenced 150,000 base pairs of nuclear DNA divided among 15 autosomal regions as well as the complete mitochondrial genomes from 20 bonobos and 58 chimpanzees. Except for western chimpanzees, we found poor genetic separation of chimpanzees based on sample locality. In contrast, bonobos consistently cluster together but fall as a group within the variation of chimpanzees for many of the regions. Thus, while chimpanzees retain genomic variation that predates bonobo-chimpanzee speciation, extensive lineage sorting has occurred within bonobos such that much of their genome traces its ancestry back to a single common ancestor that postdates their origin as a group separate from chimpanzees.

Long-Term Balancing Selection in LAD1 Maintains a Missense Trans-Species Polymorphism in Humans, Chimpanzees, and Bonobos

Abstract: Balancing selection maintains advantageous genetic and phenotypic diversity in populations. When selection acts for long evolutionary periods selected polymorphisms may survive species splits and segregate in present-day populations of different species. Here, we investigate the role of long-term balancing selection in the evolution of protein-coding sequences in the Homo-Pan clade. We sequenced the exome of 20 humans, 20 chimpanzees, and 20 bonobos and detected eight coding trans-species polymorphisms (trSNPs) that are shared among the three species and have segregated for approximately 14 My of independent evolution. Although the majority of these trSNPs were found in three genes of the major histocompatibility locus cluster, we also uncovered one coding trSNP (rs12088790) in the gene LAD1. All these trSNPs show clustering of sequences by allele rather than by species and also exhibit other signatures of long-term balancing selection, such as segregating at intermediate frequency and lying in a locus with high genetic diversity. Here, we focus on the trSNP in LAD1, a gene that encodes for Ladinin-1, a collagenous anchoring filament protein of basement membrane that is responsible for maintaining cohesion at the dermal-epidermal junction; the gene is also an autoantigen responsible for linear IgA disease. This trSNP results in a missense change (Leucine257Proline) and, besides altering the protein sequence, is associated with changes in gene expression of LAD1.

Comparative Population Genomics of the Ejaculate in Humans and the Great Apes

Abstract: The rapid molecular evolution of reproductive genes is nearly ubiquitous across animals, yet the selective forces and functional targets underlying this divergence remain poorly understood. Humans and closely related species of great apes show strongly divergent mating systems, providing a powerful system to investigate the influence of sperm competition on the evolution of reproductive genes. This is complemented by detailed information on male reproductive biology and unparalleled genomic resources in humans. Here, we have used custom microarrays to capture and sequence 285 genes encoding proteins present in the ejaculate as well as 101 randomly selected control genes in 21 gorillas, 20 chimpanzees, 20 bonobos, and 20 humans. In total, we have generated >25� average genomic coverage per individual for over 1 million target base pairs. Our analyses indicate high levels of evolutionary constraint across much of the ejaculate combined with more rapid evolution of genes involved in immune defense and proteolysis. We do not find evidence for appreciably more positive selection along the lineage leading to bonobos and chimpanzees, although this would be predicted given more intense sperm competition in these species. Rather, the extent of positive and negative selection depended more on the effective population sizes of the species. Thus, general patterns of male reproductive protein evolution among apes and humans depend strongly on gene function but not on inferred differences in the intensity of sperm competition among extant species.

Fast Tree: Computing Large Minimum-Evolution Trees with Profiles instead of a Distance Matrix

Abstract: Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.

Harnessing the power of RADseq for ecological and evolutionary genomics

Abstract: High-throughput techniques based on restriction site-associated DNA sequencing (RADseq) are enabling the low-cost discovery and genotyping of thousands of genetic markers for any species, including non-model organisms, which is revolutionizing ecological, evolutionary and conservation genetics. Technical differences among these methods lead to important considerations for all steps of genomics studies, from the specific scientific questions that can be addressed, and the costs of library preparation and sequencing, to the types of bias and error inherent in the resulting data. In this Review, we provide a comprehensive discussion of RADseq methods to aid researchers in choosing among the many different approaches and avoiding erroneous scientific conclusions from RADseq data, a problem that has plagued other genetic marker types in the past.

Great ape genetic diversity and population history

Abstract: Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Origin of the human malaria parasite Plasmodium falciparum in gorillas

Abstract: Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin. The evolutionary origin of Plasmodium falciparum, the most prevalent and lethal of the malaria parasites infecting humans, is much debated. Genetic analysis of thousands of fecal samples from wild-living African apes show that the parasites found in the western gorillas — rather than those of chimpanzees or bonobos — are most closely related to the human parasite. The data suggest that all extant human strains of the parasite evolved from a single host transfer event. The new findings are also relevant to the current antimalaria campaign, as they point to potential Plasmodium reservoirs in apes. The evolutionary origin of the human malaria parasite Plasmodium falciparum has been much debated. Genetic analysis of a large number of faecal samples from wild-living African apes now shows that Plasmodium parasites from Western gorillas are most closely related to the human parasite. The data suggest that human P. falciparum evolved from a gorilla parasite after a single host transfer event.