We present analysis of admixture in an entire population using genetic information from nuclear and mitochondrial genomes. We developed new software that enabled quantification of the real contribution of nonindigenous variation to the island population. Delineating admixed ancestry for each sample in this cohort and for each segment along the genome allows us to distinguish two distinct waves of introduction of nonindigenous genetics to Kosrae, historical admixture from the late nineteenth to early twentieth century versus recent
admixture of first- and second-generation immigrants. Our data from the Y chromosome and mitochondrial genome confirm that the ‘historical admixture' was male introduced. Records of whaling ships visiting the island further promote the assumption that historical admixture, even in pedigrees in which we do not observe a European Y chromosome, was most likely derived from men. Other studies using uniparental markers observed primarily male-mediated European gene flow into Polynesian populations,3, 4, 5
but this is the first report for Micronesia.
Despite the large number of Kosraens showing admixture as a result of the first wave of immigration to the island, the overall extent of European ancestry in each individual is relatively low. This is primarily because of the rapid population expansion in Kosrae over the last century, as is evidenced by the large pedigrees of admixed individuals now present on the island. In addition, these large pedigrees typically have European ancestry coming from a single, male founder. Owing to the low level of admixture at the population level, efforts to map loci affecting phenotypic variation using admixture mapping would be severely underpowered.
This demographic history provides us with the opportunity to follow up European haplotypes of individual founders throughout their large pedigrees and make interesting observations on meiotic recombination rates. We observe 19 meiotic crossovers in one male individual, which is in line with observations by Cheung et al.27
We measured the length of genomic segments between recombination events. For the third generation after admixture, we observe European haplotype lengths that fit to theoretical expectation for distance between recombination events (34
cM). For the first and second generations, we observe an average European haplotype length of 68 and 41
cM, respectively, somewhat shorter than the expectation based solely on recombination. However, when only larger chromosomes are considered, the average length for k
=1 is 96
cM and for k
=2 is 50
cM, perfectly in accord with expectation.
The admixture on Kosrae was introduced relatively recently compared with other well-studied genetically admixed populations. In addition, in Kosrae, most admixture can be attributed to a relatively small number of European founders introduced into the population 5–7 generations ago. This demography results in an unusual finding of increased low-frequency alleles compared with other outbred, populations. Low-frequency alleles are typically considered as new mutations. However, in this case, they are a sign of admixture. The singletons are alleles that did not exist in the indigenous population and were brought in by Europeans. Most of these SNPs have population frequencies in the ancestral populations that reflect the signature of Ancestry Informative Markers: increased frequency in European population and low frequency in Asian population (data not shown). However, some are present in both the HapMap Asian and European populations in relatively equal frequency. The fact that these particular alleles appear as low frequency in Kosrae is most likely because of the introduction of new alleles after the bottleneck. We have not detected significant amounts of other sources of immigration to the island.
On a broader view, the cohort and data in this study provide a unique example of near complete population genetics: examination of whole-genome variation in autosomes, mitochondrial genome, and Y-chromosome markers in essentially every family on the island. It is noteworthy that some admixed pedigrees show neither a European Y nor a European mitochondrial haplogroup, resulting in ambiguity with regard to the sexual origin of this admixture. In studies that only include genetic information from uniparental markers, the European contribution to the ancestry of these individuals would be completely missed. In fact, if our study only examined mitochondrial and Y chromosomes, we would have detected European ancestry in 3% of the population, instead of the 39% we found using a complete genetic approach. Although autosomal data provided the most complete assessment of population history with regard to admixture, the information contained in the uniparental markers is not superseded. Owing to the absence of recombination in the mitochondrial genome and to the nonrecombining portion of the Y chromosome, valuable information with regard to population history is retained. These genetic segments reveal the Kosraen population history vastly deeper into the past than do autosomes, and of course reveal the sex-specific contribution to the contemporary gene pool. Studies of Polynesian29
populations using serum protein markers and HLA typing have observed the presence of European admixture, but these studies did not have genome-wide resolution and could easily have underestimated the extent of admixture. Owing to the density of our whole-genome data and to combining these data with sex-specific markers, we are better able to quantify the actual extent of European alleles in a population. These data coupled with the unique population structure in Kosrae allowed us to date with high precision the introduction of European founders to the island. Our results using a genetic approach match historical record, which dates Kosrae's first contact with Westerners to the 1820s.2
Our methodology serves as a model for studies that seek to delineate and quantify ancestry in any population.
We view this approach as a model for a near future reality of such information available for numerous, larger populations, with dynamics of heredity being observed in unprecedented detail. Although we show a successful parsing of per-locus ancestry at the individual level, this is assisted by population isolation and separation between source populations. For more challenging cohorts with genetically closer founder populations, our analysis brings forth a way to better tease apart admixed segments.