Detection of chromosomal aneuploidy in ancient genomes

Abstract

Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits.

Fig. 1. Five individuals with sex chromosomal aneuploidies detected using ancient DNA.

a R_x and R_y estimates, representing the number of sequences aligning to chromosomes X and Y, respectively, as a proportion of the sum of sequences aligned to autosomes, for 134 genomes from Antonio et al., 436 genomes from Margaryan et al. and 5 newly published individuals with sex chromosomal aneuploidies (n = 575) (Supplementary Data 2). b Map of Great Britain with the location of the five sites of origin of individuals presented in this study. c Timeline with archaeological periods of British history and prehistory, spanning from the Iron Age to the present, including dates and karyotypes of newly published individuals with sex chromosomal aneuploidies.

Fig. 2. Per chromosome coverage in five individuals with aneuploidies on the sex chromosomes and in one individual with aneuploidy on chromosome 21 from this study.

Proportion of sequences aligned on each chromosome, normalised between chromosomes and across individuals to account for differences in sequencing effort per library (Supplementary Data 3). Individuals C11119 (Sk4205 from Longwall Quad, Magdalen College), C10427 (WS224 from Wetwang Slack), C11569 (Sk30828 from Trinity Burial Ground) with a 47,XXY karyotype carried two copies of chromosome X as well as one copy of chromosome Y. Individual C10462 (WS267 from Wetwang Slack) carried a typical number of sex chromosomes (one X and one Y) and an extra copy of chromosome 21 resulting in a 47,XY, + 21 karyotype. Individual C13582 (Skeleton 16586 from Lincoln Eastern Bypass) had a 47,XYY karyotype, as indicated by the presence of only one copy of chromosome X and two copies of chromosome Y. Individual C10090 (CH163 from Charterhouse Warren) carried no copies of chromosome Y and one copy of chromosome X, with mosaicism (i.e. a minority of cells carried a 46,XX karyotype as evidenced by heterozygosity in chromosome X).

Fig. 3. An individual with mosaic Turner syndrome from Iron Age Somerset, UK.

a The cranium of the identified individual C10090 (CH163) from Charterhouse Warren (45,X0/46,XX) with mosaic Turner syndrome, exhibiting features consistent with a female morphological characterisation (full description in Supplementary Note 1). Scale bar indicates 5 cm. Image credits: Rick Schulting, Ian Cartwright. b R_x values for C10090 (45,X0/46,XX) across six different coverage levels (n = 507), dashed lines representing R_x boundaries for one copy of chromosome X. Mean is plotted as a circle, median as a horizontal line, lower and upper hinges correspond to the first and third quartiles, error bars represent ± 1 SD (Supplementary Data 4). c R_y values for C10090 (45,X0/46,XX) across six different coverage levels (n = 507), dashed lines representing R_y boundaries for no copies of chromosome Y. Mean is plotted as a circle, median as a horizontal line, lower and upper hinges correspond to the first and third quartiles, error bars represent ± 1 SD (Supplementary Data 4).