Inheritance of somatic mutations by animal offspring

Abstract
Since 1892, it has been widely assumed that somatic mutations are evolutionarily irrelevant in animals because they cannot be inherited by offspring. However, some nonbilaterians segregate the soma and germline late in development or never, leaving the evolutionary fate of their somatic mutations unknown. By investigating uni- and biparental reproduction in the coral Acropora palmata (Cnidaria, Anthozoa), we found that uniparental, meiotic offspring harbored 50% of the 268 somatic mutations present in their parent. Thus, somatic mutations accumulated in adult coral animals, entered the germline, and were passed on to swimming larvae that grew into healthy juvenile corals. In this way, somatic mutations can increase allelic diversity and facilitate adaptation across habitats and generations in animals.
Figures
Fig. 1.. Detection and mapping of somatic…
Fig. 1.. Detection and mapping of somatic mutations across a parent coral colony and five…
Fig. 1.. Detection and mapping of somatic mutations across a parent coral colony and five nearest neighbor colonies (ramets) from the same coral genet.
(A) Sampling map of the parent colony and its five nearest neighbor colonies. Colonies are arranged according to their location on the reef with linear distances between colonies indicated next to the arrows. Colored circles indicate the locations of the tissue samples that were genotyped. Individual colonies in the line drawing are enlarged to show detail and not drawn to scale. Photo credit: Kate L. Vasquez Kuntz, The Pennsylvania State University. (B) Plot of Prevosti’s pairwise genetic distance within the parent colony and between the parent colony and the five neighboring colonies. All genetic distances were smaller than the distance threshold for genet assignment; therefore, all six colonies belonged to the same coral genet. (C) Histogram showing the frequency of pairwise genetic distances for 263 A. palmata samples collected from across the Caribbean in a previous study. The genet threshold is 0.032 (dashed black line). Average genetic distance was 0.0057 ± 0.0054 among ramets of the same genet (blue line, n = 148 ramets from 34 genets). Average genetic distance was 0.128 ± 0.025 among genets that fall above the genet threshold (orange line) [modified with permission from Kitchen et al. (26)]. (D) Neighbor-joining trees for all samples taken from the parent colony (B1 to B10) and nearest neighbor colonies (C1 to C5) showing all loci analyzed (upper tree, n = 19,696) and only those loci identified as mutations (lower tree, n = 268). Nodal values represent support from 100 bootstrap replicates.
(A) Bar plot showing the number of total mutations (dark blue bars) categorized as a GOH or LOH, and the number of mutations in each category that were passed on to offspring (light blue bars). GOH mutations outnumbered LOH mutations, but a greater proportion of LOH mutations were inherited by offspring. (B) Plots of two metrics used to investigate somatic mutations: BAF (B allele frequency; top row) and LRR (log R ratios; bottom row). The orange line represents the 20-bp sliding average of LRR along the scaffold (position in megabases). Blue and black symbols represent specific mutations. Black shapes: not inherited; blue shapes: inherited. Above each plot, adult coral colonies are labeled as in Fig. 1A and juveniles are denoted as “Offspring”. Sample labels are filled according to specific, shared mutations (light blue, locus AX-197954877; medium blue, locus AX-212313644). Samples without those mutations have a white label fill. (C) RFLP validation of inherited GOH mutation AX-212313644. For each sample, the uncut (U) and cut (C) polymerase chain reaction products are shown next to a size standard (lane M). The two offspring (179 and 181) both share the heterozygous mutation also detected in colony 3, resulting in three bands, while colony 5, predicted to have the nonmutant homozygous state for this site, produced only one uncut band. (D) Schematic of inheritance of somatic mutations. RFLP-validated somatic mutation AX-212313644 (down triangle) is found within the intron of the dynein heavy chain 3. GOH mutation AX-197954877 (square) is found on the same scaffold. Symbols represent the five mutations detected along this scaffold in at least one sample in (B). Filled shapes, A allele; open shapes, B allele. Arrows denote inheritance and crosses denote lack of inheritance. Offspring 144 was parthenogenetic (denoted by an asterisk).
Biparental offspring resulted from a cross between the focal A. palmata parent colony in Curaçao and a Florida colony whose sperm had been cryopreserved (27). Previously identified somatic mutations at 268 loci in the Curaçao parent were tracked into 11 outcrossed biparental offspring that were identified during genotyping (n = 11). Most loci matched the expectations of Mendelian inheritance for the Curaçao ancestral allele [(A), 73.5%]. At the remaining loci, offspring either putatively inherited the Curaçao mutant allele [(B), 15.3%] or exhibited unexpected inheritance patterns inconsistent with the Curaçao ancestral or mutant allele [(C), 11.1%]. For example, at locus AX-212300259, one offspring had an unexpected mutant AA genotype, while the parent from Florida did not have an A allele to contribute. These unexpected alleles in the offspring may have resulted from technical errors (26) or represent de novo (germline) mutations (19, 35). n/a, no mutant allele detected.
Fig. 4.. Modes of inheritance of genetic…
Fig. 4.. Modes of inheritance of genetic mutations in animals.
( 1 ) If animals…
Fig. 4.. Modes of inheritance of genetic mutations in animals.
(1) If animals differentiate and segregate germline cells (light blue) from somatic cells (light orange) early in development, then only germline mutations (medium blue) can be inherited by offspring (1). (2) Planarians, sponges, and some cnidarians continuously segregate a germline and somatic tissue from a population of stem cells (brown) as they grow, allowing for an accumulation of mutations that are heritable (11). (3) Cnidarian somatic cells may de- or transdifferentiate into germline cells, passing on mutations that are somatic in origin (dark blue) (14). The cellular source (soma, germ, or stem) for polyp growth is an active area of research. (4) Somatic mutations (dark orange) may rise to fixation in new modules (polyps) through budding from a limited number of soma cells. Lightning bolts represent mutation-causing events. Figure modified with permission from Reusch et al. (21).