I am a scientist specialized in mitochondria and genetics, but above all, I am just curious guy who loves learning new things.


Besides global exchange of goods and money, how about exchanging some genes…

In 10 seconds? Globalization has made distances shorter, making it easier than ever before for people from all over the globe to meet. The genetic admixture resulting from this encounter of human groups from different ancestral source populations could be creating completely novel human genomes, boosting natural selection and evolution.

But how is this faster than “regular” natural selection? Natural selection is a slow process based on novel random mutations that may give an advantage in a given environment, allowing a higher reproduction rate for the individuals carrying these mutations. Thereby, after thousands of years, an important part of a population will carry the mutation and the advantage it confers. But when people from different genetic backgrounds meet (in the biblical sense) there could be a selection from pre-existing population specific alleles, which have already been selected in their ancestral regions. The slow process of natural selection has already occurred, and the pre-existing adapted alleles are ready to be rapidly re-assorted to fit any new selective pressures.

Are there any actual examples of this “boosted” natural selection? One known example is the hybridization that existed between Homo sapiens and other archaic Homo species, which provided us an important reservoir of advantageous alleles that enabled adaptation to the different regions of the globe. But the best recent example is the genetic admixture that resulted from the encounter of Native Americans, Europeans and Africans after the arrival of Columbus to the New World. This resulted in completely new genomes, that “picked” from the three ancestral origins the genomic regions they needed to better survive in the new environment.

And what did they pick? For instance, immune system related genes involved in defense against endemic pathogens such as malaria, for which the alleles from African genomes were highly selected.


Long-distance dispersal suppresses introgression of local alleles during range expansions.

Abstract: During range expansions, even low levels of interbreeding can lead to massive introgression of local alleles into an invader's genome. Nonetheless, this pattern is not always observed in human populations. For instance, European Americans in North America are barely introgressed by Amerindian genes in spite of known contact and admixture. With coalescent spatially explicit simulations, we examined the impact of long-distance dispersal (LDD) events on introgression of local alleles into the invading population using a set of different demographic scenarios applicable to a diverse range of natural populations and species. More specifically, we consider two distinct LDD models: one where LDD events originate in the range core and targets only the expansion front and a second one where LDD events can occur from any area to any other. We find that LDD generally prevents introgression, but that LDD events specifically targeting the expansion front are most efficient in suppressing introgression. This is likely due to the fact that LDD allows for the presence of a larger number of invader alleles at the wave front, where effective population size is thus increased and local introgressed alleles are rapidly outnumbered. We postulate that the documented settlement of pioneers directly on the wave front in North America has contributed to low levels of Amerindian admixture observed in European Americans and that this phenomenon may well explain the lack of introgression after a range expansion in natural populations without the need to evoke other mechanisms such as natural selection.Heredity advance online publication, 31 August 2016; doi:10.1038/hdy.2016.68.

Pub.: 01 Sep '16, Pinned: 17 Aug '17

Implications of human evolution and admixture for mitochondrial replacement therapy.

Abstract: Mitochondrial replacement (MR) therapy is a new assisted reproductive technology that allows women with mitochondrial disorders to give birth to healthy children by combining their nuclei with mitochondria from unaffected egg donors. Evolutionary biologists have raised concerns about the safety of MR therapy based on the extent to which nuclear and mitochondrial genomes are observed to co-evolve within natural populations, i.e. the nuclear-mitochondrial mismatch hypothesis. In support of this hypothesis, a number of previous studies on model organisms have provided evidence for incompatibility between nuclear and mitochondrial genomes from divergent populations of the same species.We tested the nuclear-mitochondrial mismatch hypothesis for humans by observing the extent of naturally occurring nuclear-mitochondrial mismatch seen for 2,504 individuals across 26 populations, from 5 continental populations groups, characterized as part of the 1000 Genomes Project (1KGP). We also performed a replication analysis on mitochondrial DNA (mtDNA) haplotypes for 1,043 individuals from 58 populations, characterized as part of the Human Genome Diversity Project (HGDP). Nuclear DNA (nDNA) and mtDNA sequences from the 1KGP were directly compared within and between populations, and the population distributions of mtDNA haplotypes derived from both sequence (1KGP) and genotype (HGDP) data were evaluated. Levels of nDNA and mtDNA pairwise sequence divergence are highly correlated, consistent with their co-evolution among human populations. However, there are numerous cases of co-occurrence of nuclear and mitochondrial genomes from divergent populations within individual humans. Furthermore, pairs of individuals with closely related nuclear genomes can have highly divergent mtDNA haplotypes. Supposedly mismatched nuclear-mitochondrial genome combinations are found not only within individuals from populations known to be admixed, where they may be expected, but also from populations with low overall levels of observed admixture.These results show that mitochondrial and nuclear genomes from divergent human populations can co-exist within healthy individuals, indicating that mismatched nDNA-mtDNA combinations are not deleterious or subject to purifying selection. Accordingly, human nuclear-mitochondrial mismatches are not likely to jeopardize the safety of MR therapy.

Pub.: 10 Feb '17, Pinned: 15 Aug '17

Ancestry, admixture and fitness in Colombian genomes.

Abstract: The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%-96.7%), followed by Native American (average = 18.1%, range = 2.1%-33.3%) and African (average = 7.3%, range = 0.2%-38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment.

Pub.: 22 Jul '15, Pinned: 15 Aug '17

The Columbian Exchange as a source of adaptive introgression in human populations

Abstract: The term “Columbian Exchange” refers to the massive transfer of life between the Afro-Eurasian and American hemispheres that was precipitated by Columbus’ voyage to the New World. The Columbian Exchange is widely appreciated by historians, social scientists and economists as a major turning point that had profound and lasting effects on the trajectory of human history and development.I propose that the Columbian Exchange should also be appreciated by biologists for its role in the creation of novel human genomes that have been shaped by rapid adaptive evolution. Specifically, I hypothesize that the process of human genome evolution stimulated by the Columbian Exchange was based in part on selective sweeps of introgressed haplotypes from ancestral populations, many of which possessed pre-evolved adaptive utility based on regional-specific fitness and health effects.Testing of this hypothesis will require comparative analysis of genome sequences from putative ancestral source populations, with genomes from modern admixed populations, in order to identify ancestry-specific introgressed haplotypes that exist at higher frequencies in admixed populations than can be expected by chance alone. Investigation of such ancestry-enriched genomic regions can be used to provide clues as to the functional roles of the genes therein and the selective forces that have acted to increase their frequency in the population.Critical interrogation of this hypothesis could serve to underscore the important role of introgression as a source of adaptive alleles and as a driver of evolutionary change, and it would highlight the role of admixture in facilitating rapid human evolution.This article was reviewed by Frank Eisenhaber, Lakshminarayan Iyer and Igor B. Rogozin

Pub.: 02 Apr '16, Pinned: 15 Aug '17