Richard Cordaux

Human Genomic Deletions Mediated by Recombination between Alu Elements

Recombination between Alu elements results in genomic deletions associated with many human genetic disorders. Here, we compare the reference human and chimpanzee genomes to determine the magnitude of this recombination process in the human lineage since the human-chimpanzee divergence approximately 6 million years ago. Combining computational data mining and wet-bench experimental verification, we identified 492 human-specific deletions (for a total of approximately 400 kb) attributable to this process, a significant component of the insertion/deletion spectrum of the human genome. The majority of the deletions (295 of 492) coincide with known or predicted genes (including 3 that deleted functional exons, as compared with orthologous chimpanzee genes), which implicates this process in creating a substantial portion of the genomic differences between humans and chimpanzees. Overall, we found that Alu recombination-mediated genomic deletion has had a much higher impact than was inferred from previously identified isolated events and that it continues to contribute to the dynamic nature of the human genome.

Melanesian and Asian origins of Polynesians: mtDNA and Y chromosome gradients across the Pacific

The human settlement of the Pacific Islands represents one of the most recent major migration events of mankind. Polynesians originated in Asia according to linguistic evidence or in Melanesia according to archaeological evidence. To shed light on the genetic origins of Polynesians, we investigated over 400 Polynesians from 8 island groups, in comparison with over 900 individuals from potential parental populations of Melanesia, Southeast and East Asia, and Australia, by means of Y chromosome (NRY) and mitochondrial DNA (mtDNA) markers. Overall, we classified 94.1% of Polynesian Y chromosomes and 99.8% of Polynesian mtDNAs as of either Melanesian (NRY-DNA: 65.8%, mtDNA: 6%) or Asian (NRY-DNA: 28.3%, mtDNA: 93.8%) origin, suggesting a dual genetic origin of Polynesians in agreement with the Slow Boat hypothesis. Our data suggest a pronounced admixture bias in Polynesians toward more Melanesian men than women, perhaps as a result of matrilocal residence in the ancestral Polynesian society. Although dating methods are consistent with somewhat similar entries of NRY/mtDNA haplogroups into Polynesia, haplotype sharing suggests an earlier appearance of Melanesian haplogroups than those from Asia. Surprisingly, we identified gradients in the frequency distribution of some NRY/mtDNA haplogroups across Polynesia and a gradual west-to-east decrease of overall NRY/mtDNA diversity, not only providing evidence for a west-to-east direction of Polynesian settlements but also suggesting that Pacific voyaging was regular rather than haphazard. We also demonstrate that Fiji played a pivotal role in the history of Polynesia: humans probably first migrated to Fiji, and subsequent settlement of Polynesia probably came from Fiji.

Mitochondrial DNA analysis reveals diverse histories of tribal populations from India

We analyzed 370u2009bp of the first hypervariable region of the mitochondrial DNA (mtDNA) control region in 752 individuals from 17 tribal and four nontribal groups from the Indian subcontinent, to address questions concerning the origins, genetic structure and relationships of these groups. Southern Indian tribes showed reduced diversity and large genetic distances, both among themselves and when compared with other groups, and no signal of prehistoric demographic expansions. These results probably reflect enhanced genetic drift because of small population sizes and/or bottlenecks in these groups. By contrast, northern groups exhibited more diversity and signals of prehistoric demographic expansions. Phylogenetic analyses revealed that southern and northern groups (except northeastern ones) have related mtDNA sequences albeit at different frequencies, further supporting the larger impact of drift on the genetic structure of southern groups. The Indian mtDNA gene pool appears to be more closely related to the east Eurasian gene pool (including central, east and southeast Asian populations) than the west Eurasian one (including European and Caucasian populations). Within India, northeastern tribes are quite distinct from other groups; they are more closely related to east Asians than to other Indians. This is consistent with linguistic evidence in that these populations speak Tibeto-Burman languages of east Asian origin. Otherwise, analyses of molecular variance suggested that caste and tribal groups are genetically similar with respect to mtDNA variation.

Independent origins of Indian caste and tribal paternal lineages

The origins of the nearly one billion people inhabiting the Indian subcontinent and following the customs of the Hindu caste system are controversial: are they largely derived from Indian local populations (i.e. tribal groups) or from recent immigrants to India? Archaeological and linguistic evidence support the latter hypothesis, whereas recent genetic data seem to favor the former hypothesis. Here, we analyze the most extensive dataset of Indian caste and tribal Y chromosomes to date. We find that caste and tribal groups differ significantly in their haplogroup frequency distributions; caste groups are homogeneous for Y chromosome variation and more closely related to each other and to central Asian groups than to Indian tribal or any other Eurasian groups. We conclude that paternal lineages of Indian caste groups are primarily descended from Indo-European speakers who migrated from central Asia approximately 3,500 years ago. Conversely, paternal lineages of tribal groups are predominantly derived from the original Indian gene pool. We also provide evidence for bidirectional male gene flow between caste and tribal groups. In comparison, caste and tribal groups are homogeneous with respect to mitochondrial DNA variation, which may reflect the sociocultural characteristics of the Indian caste society.

Mitochondrial DNA and Y-chromosome variation in the caucasus.

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y‐haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male‐mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.

Genetic structure and affinities among tribal populations of southern India: a study of 24 autosomal DNA markers

We describe the genetic structure and affinities of five Dravidian‐speaking tribal populations inhabiting the Nilgiri hills of Tamil Nadu, in south India, using 24 autosomal DNA markers. Our goals were: (i) to examine what evolutionary forces have most significantly impacted south Indian tribal genetic variation, and (ii) to test whether the phenotypic similarities of some south Indian tribal groups to Africans represent a signature of close relationship to Africans or are due to convergence. All loci were polymorphic and average heterozygosities were substantial (range: 0.347–0.423). Genetic differentiation was high (Gst= 6.7%) and genetic distances were not significantly correlated with geographic distances. Genetic drift therefore probably played a significant role in shaping the patterns of genetic variation observed in southern Indian tribal populations. Otherwise, analyses of population relationships showed that Indian populations are closely related to one another, regardless of phenotypic characteristics, and do not show particular affinities to Africans. We conclude that the phenotypic similarities of some Indian groups to Africans do not reflect a close relationship between these groups, but are better explained by convergence.

South Asia, the Andamanese, and the Genetic Evidence for an “Early” Human Dispersal out of Africa

We thank David Hughes, Manfred Kayser, Vano Nasidze, and Brigitte Pakendorf for critical reading of the manuscript.

Teaching an old dog new tricks : SINEs of canine genomic diversity

With >400 recognized breeds worldwide and a recently completed draft genomic sequence, the dog has emerged as a model organism of choice for the genetic dissection of morphological traits and diseases (1–3). Of great interest is the fact that a number of disorders in purebred dogs are also of human medical relevance (1, 2). In this context, the study by Clark et al. (4) in this issue of PNAS is exciting because of its implications on morphological, medical, and evolutionary grounds. Indeed, the authors have discovered a mutation in the dog SILV gene that is responsible for merle, a color patterning in the coat of various canine breeds. Strikingly, merle dogs exhibit auditory and ophthalmologic abnormalities similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome, which accounts for 2–5% of all human cases of congenital deafness (5).nnThe different dog breeds were established within the past few centuries from small numbers of founding individuals. As a consequence, linkage disequilibrium within the genome extends over at least 50-fold greater distances in dogs as compared to humans (3). Taking advantage of this feature of the dog genome, Clark et al. (4) carried out a whole-genome scan using the Shetland Sheepdog and were able to map the merle locus to the dog homologue of human chromosome 12q13. Characterization of the pigment gene SILV (6) located in this region revealed the presence of a short interspersed element (SINE) inserted at an intron/exon boundary that segregates with the merle phenotype (4). SINEs are “jumping genes” belonging to the retrotransposon class of mobile elements that propagate in their host genomes via a “copy and paste” mechanism (7–11). Because only a small fraction of mammalian genomes is functional, most retrotransposon insertions occur in genomic regions where they essentially induce …

Modeling the amplification dynamics of human Alu retrotransposons

Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA) that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human–chimpanzee divergence.

Y-STR haplotypes from eight south Indian groups based on five loci

Five Y-chromosome short tandem repeat (STR) loci (DYS389I, DYS389II, DYS390, DYS391, and DYS393) were typed in 81 males from seven tribal populations of south India, including 30 Koragas, 23 Yeravas, 5 Mullukurunan, 2 Mullukurumba, 4 Paniya, 3 Kuruchian and 3 Bettakurumba; and 11 south Indian caste individuals of mixed origins.