- Email: [email protected]
Inbreeding: When Parents Transmit More Than Genes
Current Biology Vol 16 No 18 R810
therefore, identifying factors that bind the carboxyl terminus and understanding how binding is regulated are critical questions. Finally, if Sfi1 assembly on the half-bridge is the initial event in SPB duplication, especially if that assembly is regulated as a licensing event, it will be very interesting to learn if these roles for Sfi1 are conserved during vertebrate centrosome duplication. Recent experiments suggest that a contributing factor in licensing centrosome duplication is the disengagement of the centrioles from each other at the end of mitosis [14,15]. It is likely that, as with DNA replication, a number of mechanisms will be uncovered that act together to protect the integrity of the genome, in this case, by ensuring the bipolarity of the mitotic spindle.
2.
3.
4.
5.
6.
7.
8.
References 1. Salisbury, J.L., Baron, A., Surek, B., and Melkonian, M. (1984). Striated flagellar roots: Isolation and partial
9.
characterization of a calcium-modulated contractile organelle. J. Cell Biol. 99, 962–970. Salisbury, J. (1995). Centrin, centrosomes, and mitotic spindle poles. Curr. Biol. 7, 39–45. Salisbury, J., Suino, K., Busby, R., and Springett, M. (2002). Centrin-2 is required for centriole duplication in mammalian cells. Curr. Biol. 12, 1287–1292. Kilmartin, J.V. (2003). Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication. J. Cell Biol. 162, 1211–1221. Li, S., Sandercock, A.M., Conduit, P., Robinson, C.V., Williams, R.L., and Kilmartin, J.V. (2006). Structural role of Sfi1p-centrin filaments in budding yeast spindle pole body duplication. J. Cell Biol. 173, 867–877. Cheney, R.E., and Mooseker, M.S. (1992). Unconventional myosins. Curr. Opin. Cell Biol. 4, 27–35. Ivanovska, I., and Rose, M.D. (2001). Fine structure analysis of the yeast centrin, Cdc31p, identifies residues specific for cell morphology and spindle pole body duplication. Genetics 157, 503–518. Jaspersen, S.L., and Winey, M. (2004). The budding yeast spindle pole body: Structure, duplication, and function. Annu. Rev. Cell Dev. Biol. 20, 1–28. Byers, B., and Goetsch, L. (1975). Behavior of spindles and spindle plaques in the cell cycle and conjugation of
Inbreeding: When Parents Transmit More Than Genes Inbreeding in wild populations can have devastating effects on fitness, but the genetic causes should not be transmitted across generations. A new study of song sparrows has revealed a parent–offspring resemblance for inbreeding, resulting from population structuring, with important implications for understanding the genetic causes of phenotypic variation in wild populations. Marta Szulkin and Ben C. Sheldon According to the standard model of inheritance, diploid sexual organisms inherit genes, not genotypes [1]. Genes inherited from each parent combine in offspring to produce genotypes, and thus the phenotypes, upon which natural or sexual selection acts. A resurgent theme in evolutionary biology at present is the use of various methods of genetic analysis, from quantitative genetics to functional genomics [2–4], to partition variation in the phenotypes observed in populations, and thus to understand the genetic causes
of variation within and between populations. Very often, the focus in such analysis is on genes with additive effect, because such genetic effects are transmitted directly from parent to offspring, underlie the expected response to selection on a character [5], and are much easier to quantify than non-additive effects such as dominance or epistasis [1]. But phenotypes can also be influenced by interactions of genes from the two parents. These would seem to be of less interest for such analyses, for the simple reason that they cannot be transmitted directly to future generations. A recent study of inbreeding in song sparrows by
10.
11.
12.
13.
14.
15.
Saccharomyces cerevisiae. Bacteriol. 124, 511–523. Adams, I.R., and Kilmartin, J.V. (1999). Localization of core spindle pole body (SPB) components during SPB duplication in Saccharomyces cerevisiae. J. Cell Biol. 145, 809–823. Bell, S.P., and Dutta, A. (2002). DNA replication in eukaryotic cells. Annu. Rev. Biochem. 71, 333–374. Devault, A., Vallen, E.A., Yuan, T., Green, S., Bensimon, A., and Schwob, E. (2002). Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae. Curr. Biol. 12, 689–694. Haase, S.B., Winey, M., and Reed, S.I. (2001). Multi-step control of spindle pole body duplication by cyclindependent kinase. Nat. Cell Biol. 3, 38–42. Tsou, M.-F.B., and Stearns, T. (2006). Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947–951. Tsou, M.-F.B., and Stearns, T. (2006). Controlling centrosome number: licenses and blocks. Curr. Opin. Cell Biol. 18, 74–78.
MCD Biology, University of Colorado – Boulder, 347 UCB, Boulder, Colorado 80309-0347, USA. E-mail: [email protected] DOI: 10.1016/j.cub.2006.08.041
Reid et al. [6], however, has come up with evidence for the apparent transmission of what can be treated as an interactive genetic effect. This finding challenges our assumptions about the methods that we use to explain variation in natural populations. Inbreeding occurs when individuals that share a common ancestor mate. As we all share a common ancestor at some stage in our evolutionary history, we are all inbred in some sense. But it is ‘close’ inbreeding, such as matings between parents and offspring, or between siblings, that can have particularly dramatic effects on fitness, and it is the robustness and size of these effects — termed inbreeding depression — that presumably underlies incest avoidance in humans, and inbreeding avoidance in animals [7]. A number of long-term studies of wild mammal and bird populations have recently been able to quantify cases of close inbreeding between individuals known, from pedigrees, to be relatives [7–9].
Dispatch R811
A
B 0.4
Offspring's inbreeding coefficient (f)
Such close inbreeding is generally rare, requiring large populations, studied for a long time, to accumulate enough information to quantify the effects of inbreeding. When it does occur, the effects of inbreeding (inbreeding depression) can be dramatic; for example, mating between first order relatives in the collared flycatcher Ficedula albicollis was found to reduce fitness by 93% [9]. Now, an individual’s inbreeding coefficient (f ) is simply the probability that two alleles are identical by descent, derived from a common ancestor. Because it is dependent on the relationship between the genomes of parents, which must be close relatives to yield a high inbreeding coefficient, it seems obvious that however severe the effects of inbreeding depression are on an individual, those effects will be wiped clean, at least in genetic terms, in the offspring of an inbred individual. It is this expectation that is contradicted by the new study of Reid et al. [6]. By studying a population of song sparrows, Melospiza melodia (Figure 1A), inhabiting a small island (Mandarte) in British Columbia, they were able to make full use of an excellent pedigree, enabling accurate estimation of the relatedness of almost all individuals in the population, and the consequent inbreeding coefficient of their offspring. This population is isolated, but not closed: a few individuals immigrate each year, and because this is a common species distributed widely all around the neighbouring islands, immigrants are reasonably assumed to be unrelated to any of the residents on the island, and therefore outbred with respect to the island population. The analysis of 15 years’ worth of breeding attempts revealed a highly significant correlation between the inbreeding coefficients of parents and offspring [6]. Inbred sparrows were found to have, on average, relatively inbred offspring, while outbred parents relatively outbred offspring (Figure 1B). This effect was significant whether restricted to mother–offspring or
0.3
0.2
0.1
0.0 0.00
Current Biology
0.05
0.10
0.15
0.20
0.25
Midparent inbreeding coefficient (f)
Figure 1. Parent and offspring inbreeding coefficients are correlated. (A) A song sparrow, member of the species studied by Reid et al. [6], who found that parents that are inbred themselves produce offspring that are inbred. (B) The relationship between offspring inbreeding coefficient (f) and midparent f across all song sparrow pairings studied by Reid et al. [6] over a 15-year period. Offspring f was positively correlated with midparent f (r = 0.34, N = 315, P < 0.001). (Panel B adapted with permission from [6].)
father–offspring inbreeding coefficients, for the majority of individual years, despite these providing many fewer data points, and even when very close inbreeding events were excluded. Of key interest is the way that the correlation between parent f and offspring f arose: because immigrants were known, and could be distinguished from locally born sparrows, it could be shown that a parent–offspring inbreeding correlation can arise simply from the random mixing of immigrants with resident, locally born birds. Immigrants, which are outbred relative to the Mandarte Island population, by definition mate with unrelated individuals, yielding offspring that are themselves both outbred and relatively unrelated to the native Mandarte individuals with which they subsequently mated. In contrast, locally born birds, which overall have relatively high levels of inbreeding [8], are related to the majority of the birds on the island and thus have a high chance of mating with an individual that is inbred, but also a relative. This, in turn, results in offspring that are inbred. Many contemporary natural populations inhabit increasingly fragmented habitats, and when immigrants end up mixing with members of a relatively isolated population, it is not unlikely that parent f–offspring f correlations may commonly arise as a result of population structure alone. Indeed, the population genetic consequences of habitat
structuring, and the way that it interacts with dispersal of individual organisms, is an area of considerable current interest [10–12]. Although mate-choice simulations using different models of kinship have demonstrated that parent–offspring correlations for inbreeding can arise simply through random mating, Reid et al. [6] found evidence that the correlation was in fact higher than expected from random mating. By comparing patterns of mating with the kinship of available mates, they showed that inbred sparrows paired with more closely related mates than expected if mating was entirely random. This leaves us with a puzzling question: given a choice, and given the fitness cost of inbreeding [8], why would inbred individuals prefer to mate with relatives, thus producing offspring that suffer the same fitness costs as do they themselves? Potential explanations are numerous: non-random inbreeding could arise because inbreeding depression depresses the ability to recognise kin, because mating preferences with respect to avoiding kin are inherited, or because of constraints on mate choice. Alternatively, a novel perspective is provided by the fact that there may also be scope for kin-selected benefits of incestuous mating [13]. Irrespective of whether the relationship between parent– offspring inbreeding coefficient results from random mating in a heavily structured population, or
Current Biology Vol 16 No 18 R812
is exacerbated by non-random pairing, the demonstration of such a strong relationship between parent and offspring inbreeding coefficients has important implications for the way that we interpret the causes of variation in natural populations. For example, if parents that inbreed are themselves inbred, then this may lead to over-estimation of the magnitude of inbreeding depression, because part of the estimated effect of inbreeding in offspring might be attributable to inbreeding in parents [14,15]. The magnitude of inbreeding depression is of considerable importance for our understanding of the genetic architecture of quantitative traits [16], and the evolution of dispersal, kin recognition and other potential inbreeding avoidance mechanisms [7]. Secondly, a parent–offspring inbreeding correlation would lead to the overestimation of the size of additive genetic effects for those traits that are more strongly influenced by inbreeding. Worryingly, the traits that show the strongest inbreeding depression tend to be those on which selection acts most strongly [17], and for which understanding the genetic basis of traits provides the biggest challenge [18,19]. It may turn out that the very high parent–offspring resemblance for
inbreeding found by Reid et al. [6] is a special characteristic of small island populations with low rates of immigration, but until that is established, biologists interested in understanding the causes of variation in wild populations should spend more time considering the relationships between inbreeding, relatedness and population structure in wild populations.
1. Falconer, D.S., and Mackay, T.F.C. (1996). Introduction to Quantitative Genetics (Harlow: Prentice Hall). 2. Kruuk, L.E.B. (2004). Estimating genetic parameters in natural populations using the ‘‘animal model’’. Phil. Trans. R. Soc. B 359, 873–890. 3. Slate, J. (2005). Quantitative trait locus mapping in natural populations: progress, caveats and future directions. Mol. Ecol. 14, 363–379. 4. Abzhanov, A., Protas, M., Grant, B.R., Grant, P.R., and Tabin, C.J. (2004). Bmp4 and morphological variation of beaks in Darwin’s finches. Science 305, 1462–1465. 5. Price, G.R. (1970). Selection and Covariance. Nature 227, 520–521. 6. Reid, J.M., Arcese, P., and Keller, L.F. (2006). Intrinsic parent-offspring correlation in inbreeding level in a song sparrow (Melospiza melodia) population open to immigration. Am. Nat., in press. 7. Keller, L.F., and Waller, D.M. (2002). Inbreeding effects in wild populations. Trends Ecol. Evol. 17, 230–241. 8. Keller, L.F. (1998). Inbreeding and its fitness effects in an insular population of song sparrows (Melospiza melodia). Evolution 52, 240–250. 9. Kruuk, L.E.B., Sheldon, B.C., and Merila, J. (2002). Severe inbreeding depression in collared flycatchers (Ficedula albicollis). Proc. R. Soc. Lond. B 269, 1581–1589. 10. Postma, E., and van Noordwijk, A.J. (2005). Gene flow maintains large genetic
Uptake of Ca2+ by mitochondria serves as a regulator of a number of important cellular functions, including energy metabolism, cytoplasmic Ca2+ signals, and apoptosis. Recent findings reveal that the process of Ca2+ uptake by the mitochondrial uniporter is itself regulated by Ca2+ in a temporally complex manner.
The history of Ca2+ handling by mitochondria is a classic story of rags to riches (or rather riches to rags to riches) [1]. In the 1970s to early 1980s, mitochondria were
12.
13. 14.
References
Calcium Signaling: Double Duty for Calcium at the Mitochondrial Uniporter
James W. Putney, Jr.1 and Andrew P. Thomas2
11.
thought to be prime sources of signaling Ca2+ in non-excitable cells. However, this idea fell into disfavor with the finding that, at the Ca2+ levels expected in either resting or activated cells, the relatively high Km for uptake should preclude significant Ca2+
15.
16.
17.
18.
19.
difference in clutch size at a small spatial scale. Nature 433, 65–68. Garant, D., Kruuk, L.E.B., Wilkin, T.A., McCleery, R.H., and Sheldon, B.C. (2005). Evolution driven by differential dispersal within a wild bird population. Nature 433, 60–65. Rueness, E.K., Jorde, P.E., Hellborg, L., Stenseth, N.C., Ellegren, H., and Jakobsen, K.S. (2003). Cryptic population structure in a large, mobile mammalian predator, the Scandinavian lynx. Mol. Ecol. 12, 2623–2633. Kokko, H., and Ots, I. (2006). When not to avoid inbreeding. Evolution 60, 467–475. Reid, J.M., Arcese, P., and Keller, L.F. (2003). Inbreeding depresses immune response in song sparrows (Melospia melodia): direct and inter-generational effects. Proc. R. Soc. Lond. B 272, 2151–2157. Richardson, D.S., Komdeur, J., and Burke, T. (2004). Inbreeding in the Seychelles warbler: environmentdependent maternal effects. Evolution 58, 2037–2048. Merila¨, J., and Sheldon, B.C. (1999). Genetic architecture of fitness and nonfitness traits: empirical patterns and development of ideas. Heredity 83, 103–109. de Rose, M.A., and Roff, D.A. (1999). A comparison of inbreeding depression in life history and morphological traits in animals. Evolution 53, 1288–1292. Merila¨, J., and Sheldon, B.C. (2000). Lifetime reproductive success and heritability in nature. Am. Nat. 155, 301–310. Kruuk, L.E.B., Clutton-Brock, T.H., Slate, J., Pemberton, J.M., Brotherstone, S., and Guinness, F.E. (2000). Heritability of fitness in a wild mammal population. Proc. Natl. Acad. Sci. USA 97, 698–703.
Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. E-mail: [email protected] DOI: 10.1016/j.cub.2006.08.037
accumulation by mitochondria [2], and ultimately with the finding that the signal for intracellular Ca2+ release, inositol trisphosphate (IP3), clearly mobilized Ca2+ from endoplasmic reticulum [3]. Biochemical studies of mitochondrial Ca2+ content and the regulation of mitochondrial Ca2+-sensitive enzymes indicated that mitochondria were more likely to be a target for Ca2+ signaling rather than a source [4,5]. When Rizzuto et al. [6] made the first direct in situ measurements of mitochondrial Ca2+, it was clear that receptor-activated Ca2+ signals caused rapid and large Ca2+ signals in the mitochondrial matrix. It soon became apparent that mitochondria are capable of
therefore, identifying factors that bind the carboxyl terminus and understanding how binding is regulated are critical questions. Finally, if Sfi1 assembly on the half-bridge is the initial event in SPB duplication, especially if that assembly is regulated as a licensing event, it will be very interesting to learn if these roles for Sfi1 are conserved during vertebrate centrosome duplication. Recent experiments suggest that a contributing factor in licensing centrosome duplication is the disengagement of the centrioles from each other at the end of mitosis [14,15]. It is likely that, as with DNA replication, a number of mechanisms will be uncovered that act together to protect the integrity of the genome, in this case, by ensuring the bipolarity of the mitotic spindle.
2.
3.
4.
5.
6.
7.
8.
References 1. Salisbury, J.L., Baron, A., Surek, B., and Melkonian, M. (1984). Striated flagellar roots: Isolation and partial
9.
characterization of a calcium-modulated contractile organelle. J. Cell Biol. 99, 962–970. Salisbury, J. (1995). Centrin, centrosomes, and mitotic spindle poles. Curr. Biol. 7, 39–45. Salisbury, J., Suino, K., Busby, R., and Springett, M. (2002). Centrin-2 is required for centriole duplication in mammalian cells. Curr. Biol. 12, 1287–1292. Kilmartin, J.V. (2003). Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication. J. Cell Biol. 162, 1211–1221. Li, S., Sandercock, A.M., Conduit, P., Robinson, C.V., Williams, R.L., and Kilmartin, J.V. (2006). Structural role of Sfi1p-centrin filaments in budding yeast spindle pole body duplication. J. Cell Biol. 173, 867–877. Cheney, R.E., and Mooseker, M.S. (1992). Unconventional myosins. Curr. Opin. Cell Biol. 4, 27–35. Ivanovska, I., and Rose, M.D. (2001). Fine structure analysis of the yeast centrin, Cdc31p, identifies residues specific for cell morphology and spindle pole body duplication. Genetics 157, 503–518. Jaspersen, S.L., and Winey, M. (2004). The budding yeast spindle pole body: Structure, duplication, and function. Annu. Rev. Cell Dev. Biol. 20, 1–28. Byers, B., and Goetsch, L. (1975). Behavior of spindles and spindle plaques in the cell cycle and conjugation of
Inbreeding: When Parents Transmit More Than Genes Inbreeding in wild populations can have devastating effects on fitness, but the genetic causes should not be transmitted across generations. A new study of song sparrows has revealed a parent–offspring resemblance for inbreeding, resulting from population structuring, with important implications for understanding the genetic causes of phenotypic variation in wild populations. Marta Szulkin and Ben C. Sheldon According to the standard model of inheritance, diploid sexual organisms inherit genes, not genotypes [1]. Genes inherited from each parent combine in offspring to produce genotypes, and thus the phenotypes, upon which natural or sexual selection acts. A resurgent theme in evolutionary biology at present is the use of various methods of genetic analysis, from quantitative genetics to functional genomics [2–4], to partition variation in the phenotypes observed in populations, and thus to understand the genetic causes
of variation within and between populations. Very often, the focus in such analysis is on genes with additive effect, because such genetic effects are transmitted directly from parent to offspring, underlie the expected response to selection on a character [5], and are much easier to quantify than non-additive effects such as dominance or epistasis [1]. But phenotypes can also be influenced by interactions of genes from the two parents. These would seem to be of less interest for such analyses, for the simple reason that they cannot be transmitted directly to future generations. A recent study of inbreeding in song sparrows by
10.
11.
12.
13.
14.
15.
Saccharomyces cerevisiae. Bacteriol. 124, 511–523. Adams, I.R., and Kilmartin, J.V. (1999). Localization of core spindle pole body (SPB) components during SPB duplication in Saccharomyces cerevisiae. J. Cell Biol. 145, 809–823. Bell, S.P., and Dutta, A. (2002). DNA replication in eukaryotic cells. Annu. Rev. Biochem. 71, 333–374. Devault, A., Vallen, E.A., Yuan, T., Green, S., Bensimon, A., and Schwob, E. (2002). Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae. Curr. Biol. 12, 689–694. Haase, S.B., Winey, M., and Reed, S.I. (2001). Multi-step control of spindle pole body duplication by cyclindependent kinase. Nat. Cell Biol. 3, 38–42. Tsou, M.-F.B., and Stearns, T. (2006). Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947–951. Tsou, M.-F.B., and Stearns, T. (2006). Controlling centrosome number: licenses and blocks. Curr. Opin. Cell Biol. 18, 74–78.
MCD Biology, University of Colorado – Boulder, 347 UCB, Boulder, Colorado 80309-0347, USA. E-mail: [email protected] DOI: 10.1016/j.cub.2006.08.041
Reid et al. [6], however, has come up with evidence for the apparent transmission of what can be treated as an interactive genetic effect. This finding challenges our assumptions about the methods that we use to explain variation in natural populations. Inbreeding occurs when individuals that share a common ancestor mate. As we all share a common ancestor at some stage in our evolutionary history, we are all inbred in some sense. But it is ‘close’ inbreeding, such as matings between parents and offspring, or between siblings, that can have particularly dramatic effects on fitness, and it is the robustness and size of these effects — termed inbreeding depression — that presumably underlies incest avoidance in humans, and inbreeding avoidance in animals [7]. A number of long-term studies of wild mammal and bird populations have recently been able to quantify cases of close inbreeding between individuals known, from pedigrees, to be relatives [7–9].
Dispatch R811
A
B 0.4
Offspring's inbreeding coefficient (f)
Such close inbreeding is generally rare, requiring large populations, studied for a long time, to accumulate enough information to quantify the effects of inbreeding. When it does occur, the effects of inbreeding (inbreeding depression) can be dramatic; for example, mating between first order relatives in the collared flycatcher Ficedula albicollis was found to reduce fitness by 93% [9]. Now, an individual’s inbreeding coefficient (f ) is simply the probability that two alleles are identical by descent, derived from a common ancestor. Because it is dependent on the relationship between the genomes of parents, which must be close relatives to yield a high inbreeding coefficient, it seems obvious that however severe the effects of inbreeding depression are on an individual, those effects will be wiped clean, at least in genetic terms, in the offspring of an inbred individual. It is this expectation that is contradicted by the new study of Reid et al. [6]. By studying a population of song sparrows, Melospiza melodia (Figure 1A), inhabiting a small island (Mandarte) in British Columbia, they were able to make full use of an excellent pedigree, enabling accurate estimation of the relatedness of almost all individuals in the population, and the consequent inbreeding coefficient of their offspring. This population is isolated, but not closed: a few individuals immigrate each year, and because this is a common species distributed widely all around the neighbouring islands, immigrants are reasonably assumed to be unrelated to any of the residents on the island, and therefore outbred with respect to the island population. The analysis of 15 years’ worth of breeding attempts revealed a highly significant correlation between the inbreeding coefficients of parents and offspring [6]. Inbred sparrows were found to have, on average, relatively inbred offspring, while outbred parents relatively outbred offspring (Figure 1B). This effect was significant whether restricted to mother–offspring or
0.3
0.2
0.1
0.0 0.00
Current Biology
0.05
0.10
0.15
0.20
0.25
Midparent inbreeding coefficient (f)
Figure 1. Parent and offspring inbreeding coefficients are correlated. (A) A song sparrow, member of the species studied by Reid et al. [6], who found that parents that are inbred themselves produce offspring that are inbred. (B) The relationship between offspring inbreeding coefficient (f) and midparent f across all song sparrow pairings studied by Reid et al. [6] over a 15-year period. Offspring f was positively correlated with midparent f (r = 0.34, N = 315, P < 0.001). (Panel B adapted with permission from [6].)
father–offspring inbreeding coefficients, for the majority of individual years, despite these providing many fewer data points, and even when very close inbreeding events were excluded. Of key interest is the way that the correlation between parent f and offspring f arose: because immigrants were known, and could be distinguished from locally born sparrows, it could be shown that a parent–offspring inbreeding correlation can arise simply from the random mixing of immigrants with resident, locally born birds. Immigrants, which are outbred relative to the Mandarte Island population, by definition mate with unrelated individuals, yielding offspring that are themselves both outbred and relatively unrelated to the native Mandarte individuals with which they subsequently mated. In contrast, locally born birds, which overall have relatively high levels of inbreeding [8], are related to the majority of the birds on the island and thus have a high chance of mating with an individual that is inbred, but also a relative. This, in turn, results in offspring that are inbred. Many contemporary natural populations inhabit increasingly fragmented habitats, and when immigrants end up mixing with members of a relatively isolated population, it is not unlikely that parent f–offspring f correlations may commonly arise as a result of population structure alone. Indeed, the population genetic consequences of habitat
structuring, and the way that it interacts with dispersal of individual organisms, is an area of considerable current interest [10–12]. Although mate-choice simulations using different models of kinship have demonstrated that parent–offspring correlations for inbreeding can arise simply through random mating, Reid et al. [6] found evidence that the correlation was in fact higher than expected from random mating. By comparing patterns of mating with the kinship of available mates, they showed that inbred sparrows paired with more closely related mates than expected if mating was entirely random. This leaves us with a puzzling question: given a choice, and given the fitness cost of inbreeding [8], why would inbred individuals prefer to mate with relatives, thus producing offspring that suffer the same fitness costs as do they themselves? Potential explanations are numerous: non-random inbreeding could arise because inbreeding depression depresses the ability to recognise kin, because mating preferences with respect to avoiding kin are inherited, or because of constraints on mate choice. Alternatively, a novel perspective is provided by the fact that there may also be scope for kin-selected benefits of incestuous mating [13]. Irrespective of whether the relationship between parent– offspring inbreeding coefficient results from random mating in a heavily structured population, or
Current Biology Vol 16 No 18 R812
is exacerbated by non-random pairing, the demonstration of such a strong relationship between parent and offspring inbreeding coefficients has important implications for the way that we interpret the causes of variation in natural populations. For example, if parents that inbreed are themselves inbred, then this may lead to over-estimation of the magnitude of inbreeding depression, because part of the estimated effect of inbreeding in offspring might be attributable to inbreeding in parents [14,15]. The magnitude of inbreeding depression is of considerable importance for our understanding of the genetic architecture of quantitative traits [16], and the evolution of dispersal, kin recognition and other potential inbreeding avoidance mechanisms [7]. Secondly, a parent–offspring inbreeding correlation would lead to the overestimation of the size of additive genetic effects for those traits that are more strongly influenced by inbreeding. Worryingly, the traits that show the strongest inbreeding depression tend to be those on which selection acts most strongly [17], and for which understanding the genetic basis of traits provides the biggest challenge [18,19]. It may turn out that the very high parent–offspring resemblance for
inbreeding found by Reid et al. [6] is a special characteristic of small island populations with low rates of immigration, but until that is established, biologists interested in understanding the causes of variation in wild populations should spend more time considering the relationships between inbreeding, relatedness and population structure in wild populations.
1. Falconer, D.S., and Mackay, T.F.C. (1996). Introduction to Quantitative Genetics (Harlow: Prentice Hall). 2. Kruuk, L.E.B. (2004). Estimating genetic parameters in natural populations using the ‘‘animal model’’. Phil. Trans. R. Soc. B 359, 873–890. 3. Slate, J. (2005). Quantitative trait locus mapping in natural populations: progress, caveats and future directions. Mol. Ecol. 14, 363–379. 4. Abzhanov, A., Protas, M., Grant, B.R., Grant, P.R., and Tabin, C.J. (2004). Bmp4 and morphological variation of beaks in Darwin’s finches. Science 305, 1462–1465. 5. Price, G.R. (1970). Selection and Covariance. Nature 227, 520–521. 6. Reid, J.M., Arcese, P., and Keller, L.F. (2006). Intrinsic parent-offspring correlation in inbreeding level in a song sparrow (Melospiza melodia) population open to immigration. Am. Nat., in press. 7. Keller, L.F., and Waller, D.M. (2002). Inbreeding effects in wild populations. Trends Ecol. Evol. 17, 230–241. 8. Keller, L.F. (1998). Inbreeding and its fitness effects in an insular population of song sparrows (Melospiza melodia). Evolution 52, 240–250. 9. Kruuk, L.E.B., Sheldon, B.C., and Merila, J. (2002). Severe inbreeding depression in collared flycatchers (Ficedula albicollis). Proc. R. Soc. Lond. B 269, 1581–1589. 10. Postma, E., and van Noordwijk, A.J. (2005). Gene flow maintains large genetic
Uptake of Ca2+ by mitochondria serves as a regulator of a number of important cellular functions, including energy metabolism, cytoplasmic Ca2+ signals, and apoptosis. Recent findings reveal that the process of Ca2+ uptake by the mitochondrial uniporter is itself regulated by Ca2+ in a temporally complex manner.
The history of Ca2+ handling by mitochondria is a classic story of rags to riches (or rather riches to rags to riches) [1]. In the 1970s to early 1980s, mitochondria were
12.
13. 14.
References
Calcium Signaling: Double Duty for Calcium at the Mitochondrial Uniporter
James W. Putney, Jr.1 and Andrew P. Thomas2
11.
thought to be prime sources of signaling Ca2+ in non-excitable cells. However, this idea fell into disfavor with the finding that, at the Ca2+ levels expected in either resting or activated cells, the relatively high Km for uptake should preclude significant Ca2+
15.
16.
17.
18.
19.
difference in clutch size at a small spatial scale. Nature 433, 65–68. Garant, D., Kruuk, L.E.B., Wilkin, T.A., McCleery, R.H., and Sheldon, B.C. (2005). Evolution driven by differential dispersal within a wild bird population. Nature 433, 60–65. Rueness, E.K., Jorde, P.E., Hellborg, L., Stenseth, N.C., Ellegren, H., and Jakobsen, K.S. (2003). Cryptic population structure in a large, mobile mammalian predator, the Scandinavian lynx. Mol. Ecol. 12, 2623–2633. Kokko, H., and Ots, I. (2006). When not to avoid inbreeding. Evolution 60, 467–475. Reid, J.M., Arcese, P., and Keller, L.F. (2003). Inbreeding depresses immune response in song sparrows (Melospia melodia): direct and inter-generational effects. Proc. R. Soc. Lond. B 272, 2151–2157. Richardson, D.S., Komdeur, J., and Burke, T. (2004). Inbreeding in the Seychelles warbler: environmentdependent maternal effects. Evolution 58, 2037–2048. Merila¨, J., and Sheldon, B.C. (1999). Genetic architecture of fitness and nonfitness traits: empirical patterns and development of ideas. Heredity 83, 103–109. de Rose, M.A., and Roff, D.A. (1999). A comparison of inbreeding depression in life history and morphological traits in animals. Evolution 53, 1288–1292. Merila¨, J., and Sheldon, B.C. (2000). Lifetime reproductive success and heritability in nature. Am. Nat. 155, 301–310. Kruuk, L.E.B., Clutton-Brock, T.H., Slate, J., Pemberton, J.M., Brotherstone, S., and Guinness, F.E. (2000). Heritability of fitness in a wild mammal population. Proc. Natl. Acad. Sci. USA 97, 698–703.
Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. E-mail: [email protected] DOI: 10.1016/j.cub.2006.08.037
accumulation by mitochondria [2], and ultimately with the finding that the signal for intracellular Ca2+ release, inositol trisphosphate (IP3), clearly mobilized Ca2+ from endoplasmic reticulum [3]. Biochemical studies of mitochondrial Ca2+ content and the regulation of mitochondrial Ca2+-sensitive enzymes indicated that mitochondria were more likely to be a target for Ca2+ signaling rather than a source [4,5]. When Rizzuto et al. [6] made the first direct in situ measurements of mitochondrial Ca2+, it was clear that receptor-activated Ca2+ signals caused rapid and large Ca2+ signals in the mitochondrial matrix. It soon became apparent that mitochondria are capable of